GPAT 2020

BOOKLET

PART-I
GPAT SYLLABUS
M R. AM AR M . RAVAL (M .PHARM )
PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

SYLLABUS FOR GPAT - 2020

PHARMACEUTICS

Introduction to Physical pharmacy

Mat t er, Propert ies of Mat t er:

St at e of mat t er, change in t he st at e of mat t er, lat ent heat s and vapor pressure, sublimat ion-

crit ical point , Eut ect ic mixt ures, gases, aerosols-inhalers, relat ive humidit y, liquid. Complexes,

liquid cryst als, glassy st at e, solids- cryst alline, amorphous and polymorphism.

Micromeret ics and Powder Rheology:

Part icle size and dist ribut ion, average part icle size, number and weight dist ribut ion, part icle

number, met hods f or det ermining part icle volume, met hods of det ermining part icle size- opt ical

microscopy, sieving, sediment at ion; measurement s of part icle shape, specif ic surf ace area;

met hods f or det ermining surface area; permeabilit y, adsorpt ion, derived propert ies of powders,

porosit y, packing arrangement , densit ies, bulkiness & f low propert ies.

Surface and Int erf acial Phenomenon:

Liquid int erf ace, surface and int erf acial t ensions, surf ace f ree energy, measurement of surface

and int erfacial t ensions, spreading coeff icient , adsorpt ion at liquid int erf aces, surf ace act ive

agent s, HLB classif icat ion, solubilizat ion, det ergency, adsorpt ion at solid int erf aces, solid-gas and

solid-liquid int erf aces, complex f ilms, elect rical propert ies of int erface.

Viscosit y and Rheology:

Newt onian syst ems, Law of f low, kinemat ic viscosit y, ef fect of t emperat ure; non-Newt onian

syst ems: pseudoplast ic, dilat ant , plast ic; t hixot ropy, t hixot ropy in f ormulat ion, negat ive

t hixot ropy, det erminat ion of viscosit y, capillary, f alling ball, rot at ional viscomet ers.

Dispersion Syst ems:

Colloidal dispersions: Def init ion, t ypes, propert ies of colloids, prot ect ive colloids, applicat ions of colloids in

pharmacy; Suspensions and Emulsions: Int erf acial propert ies of suspended part icles, set t ling in suspensions,

t heory of sediment at ion, eff ect of Brownian mot ion, sediment at ion of flocculat ed part icles, sediment at ion

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

paramet ers, wet t ing of part icles, cont rolled f locculat ion, f locculat ion in st ruct ured vehicles, rheological

considerat ions; Emulsions-t ypes, t heories, physical st abilit y.

Complexat ion:

Classif icat ion of complexes, met hods of preparat ion, analysis, & applicat ions.

Kinet ics and Drug St abilit y:

General considerat ions & concept s, half -lif e det erminat ion, Influence of t emperat ure, light ,

solvent , cat alyt ic species and ot her f act ors, Accelerat ed st abilit y st udy, expirat ion dat ing.

Importance of microbiology in pharmacy

St ruct ure of bact erial cell; Classif icat ion of microbes and t heir t axonomy:

Act inomycet es, bact eria, ricket t siae, spirochet es and viruses.

Ident if icat ion of Microbes:

St ains and t ypes of st aining t echniques, elect ron microscopy; Nut rit ion, cult ivat ion, isolat ion of

bact eria, act inomycet es, fungi, viruses, et c; microbial genet ics and variat ion.

Cont rol of microbes by physical and chemical met hods:

Disinf ect ion, f act ors inf luencing disinf ect ant s, dynamics of disinf ect ion, disinf ect ants and

ant isept ics and t heir evaluat ion;.

St erilizat ion:

Dif ferent met hods, validat ion of st erilizat ion met hods &equipment s; St erilit y t est ing of all

pharmaceut ical product s. Microbial assays of ant ibiot ics, vit amins & amino acids.

Immunology and Immunological Preparat ions:

Principles, ant igens and hept ans, immune syst em, cellular/ humoral immunit y, immunological

t olerance, ant igen-ant ibody react ions and t heir applicat ions. Hypersensit ivit y, act ive and passive

immunizat ion. Vaccines and sera: t heir preparat ion, st andardizat ion and st orage.

Genet ic Recombinat ion:

Transf ormat ion, conj ugat ion, t ransduct ion, prot oplast f usion and gene cloning and t heir

applicat ions.Development of hybridoma f or monoclonal ant ibodies. St udy of drugs produced by

biot echnology such as Act ivase, Humulin, Humat rope, HB et c.

Ant ibiot ics:

Hist orical development of ant ibiot ics. Ant imicrobial spect rum and met hods used f or t heir

st andardizat ion. Screening of soil f or organisms producing ant ibiot ics, f erment er, it s design,

cont rol of dif ferent paramet ers. Isolat ion of mut ant s, f act ors influencing rat e of mut at ion. Design

of f erment at ion process. Isolat ion of f erment at ion product s wit h special reference t o penicillins,

st rept omycins, t et racyclines and vit amin B12.

Introduction to pharmaceutical jurisprudence & ethics

Pharmaceut ical Legislat ions:

A brief review; Drugs & Pharmaceut ical Indust ry - A brief review; Pharmaceut ical Educat ion

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

An elaborat e st udy of t he f ollowings:

Pharmaceut ical Et hics; Pharmacy Act 1948; Drugs and Cosmet ics Act 1940 and Rules 1945;

Medicinal & Toilet Preparat ions (Excise Dut ies) Act 1955; Narcot ic Drugs & Psychot ropic

Subst ances Act 1985 & Rules; Drugs Price Cont rol Order.

A brief st udy of t he f ollowing Act s wit h special ref erence t o t he main provisions and t he lat est amendment s:

Poisons Act 1919; Drugs and Magic Remedies (Obj ect ionable Advert isement s) Act 1954; Medical

Terminat ion of Pregnancy Act 1970 & Rules 1975; Prevent ion of Cruelt y t o Animals Act 1960;

St at es Shops & Est ablishment s Act & Rules; Insect icides Act 1968; AICTE Act 1987; Fact ories Act

1948; Minimum Wages Act 1948; Pat ent s Act 1970.

A brief st udy of t he various Prescript ion/ Non-prescript ion Product s. Medical/ Surgical accessories,

diagnost ic aids, appliances available in t he market .

Introduction to dispensing and community pharmacy

Prescript ion:

Handling of prescript ion, source of errors in prescript ion, care required in dispensing procedures

including labeling of dispensed product s. General dispensing procedures including labeling of

dispensed product s; Pharmaceut ical calculat ions: Posology, calculat ion of doses f or infant s,

adult s and elderly pat ient s; Enlarging and reducing recipes percent age solut ions, alligat ion,

alcohol dilut ion, proof spirit , isot onic solut ions, displacement value et c.

Principles involved and procedures adopt ed in dispensing of :

Typical prescript ions like mixt ures, solut ions, emulsions, creams, oint ment s, powders, capsules,

past es, j ellies, supposit ories, opht halmic, past illes, lozenges, pills, lot ions, liniment s, inhalat ions,

paint s, sprays, t ablet t rit urat es, et c.

Incompat ibilit ies:

Physical and chemical incompat ibilit ies, inorganic incompat ibilit ies including incompat ibilit ies of

met als and t heir salt s, non-met als, acids, alkalis, organic incompat ibilit ies. Purine bases,

alkaloids, pyrazolone derivat ives, amino acids, quat ernary ammonium compounds, carbohydrat es,

glycosides, anest het ics, dyes, surface act ive agent s, correct ion of incompat ibilit ies. Therapeut ic

incompat ibilit ies.

Communit y Pharmacy:

Organizat ion and st ruct ure of ret ail and whole sale drug st ore-t ypes of drug st ore and design,

legal requirement s f or est ablishment , maint enance and drug st ore-dispensing of propriet ary

product s, maint enance of records of ret ail and wholesale, pat ient counseling, role of pharmacist

in communit y healt h care and educat ion (First aid, communicable diseases, nut rit ion, f amily

planning).

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Organizat ion and St ruct ure of hospit al pharmacy:

Organizat ion of a hospit al and hospit al pharmacy, Responsibilit ies of a hospit al pharmacist ,

Pharmacy and t herapeut ic commit t ee, Budget preparat ion and Implement at ion.

Hospit al Formulary:

Cont ent s, preparat ion and revision of hospit al f ormulary.

Drug St ore Management and Invent ory Cont rol:

Organizat ion of drug st ore, Types of mat erials st ocked, st orage condit ions; Purchase and

Invent ory Cont rol principles, purchase procedures, Purchase order, Procurement and st ocking.

Drug dist ribut ion Syst ems in Hospit als:

Out -pat ient dispensing, met hods adopt ed; Dispensing of drugs t o in-pat ient s. Types of drug

dist ribut ion syst ems. Charging policy, labeling; Dispensing of drugs t o ambulat ory pat ient s;

Dispensing of cont rolled drugs, Dispensing of ancillary supplies.

Cent ral St erile Supply Unit and t heir Management :

Types of mat erials f or st erilizat ion, Packing of mat erials prior t o st erilizat ion, st erilizat ion

equipment s, Supply of st erile mat erials.

Manuf act ure of St erile and Non-st erile Product s:

Policy making of manuf act urable it ems, demand and cost ing, personnel requirement s,

manufact uring pract ice, Mast er f ormula Card, product ion cont rol, Manufact uring records.

Drug Inf ormat ion Services:

Sources' of Inf ormat ion on drugs, disease, t reat ment schedules, procurement of inf ormat ion,

Comput erized services (e. g., MEDLINE), Ret rieval of inf ormat ion, Medicat ion error- t ypes of

medicat ion errors, correct ion and report ing.

Records and Report s:

Prescript ion f illing, drug prof ile, pat ient medicat ion profile, cases on drug int eract ion and

adverse react ions, idiosyncrat ic cases. Pharmacoeconomics: Int roduct ion t o pharmacoeconomics,

dif f erent met hods of pharmacoeconomics, applicat ion of pharmacoeconomics.

Pharmacoepidemiology: Def init ion and scope, met hod t o conduct pharmacoepidemiological

st udies, advant ages & disadvant ages of pharmacoepidemiological st udies.

Nuclear Pharmacy:

Met hods of handling radioisot opes, radioisot ope commit t ee.

Importance of unit operations in manufacturing, Stoichiometry:

Unit processes

Mat erial and energy balances, molecular unit s, mole fract ion, t ie subst ance, gas laws, mole

volume, primary and secondary quant it ies, equilibrium st at e, rat e process, st eady and unst eady

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

st at es, dimensionless equat ions, dimensionless f ormulae, dimensionless groups, dif f erent t ypes of

graphic represent at ion, mat hemat ical problems.

Fluid Flow:

Types of f low, Reynold's number, Viscosit y, Concept of boundary layer, basic equat ions of f luid

f low, valves, f low met ers, manomet ers and measurement of f low and pressure.

Heat t ransf er:

Concept of heat f low, applicat ions of Fourier’ s law, f orced and nat ural convect ion, surf ace

coef f icient s, boiling liquids, condensing vapors, heat exchangers, heat int erchangers, radiat ion,

black body, St ef an Bolt zmann equat ion, Kirchof f’ s law.

Evaporat ion:

Basic concept of phase equilibria, f act or af fect ing evaporat ion, evaporat ors, f ilm evaporat ors,

single ef fect and mult iple eff ect evaporat ors, Mat hemat ical problems on evaporat ion.

Dist illat ion:

Roult 's law, phase diagrams, volat ilit y; simple st eam and f lash dist illat ions, principles of

rect if icat ion, Mc-Cabe Thiele met hod f or calculat ions of number of t heoret ical plat es, Azeot ropic

and ext ract ive dist illat ion.

Drying:

Moist ure cont ent and mechanism of drying, rat e of drying and t ime of drying calculat ions;

classif icat ion and t ypes of dryers, dryers used in pharmaceut ical indust ries and special drying

met hods.

Size Reduct ion:

Def init ion, obj ect ives of size reduct ion, mechanisms of size reduct ion, f act ors aff ect ing size

reduct ion, laws governing energy and power requirement s of a mills including ball mill, hammer

mill, fluid energy mill. Size separat ion: Dif ferent t echniques of size separat ion, sieves, sieve

shakers, sediment at ion t ank, cyclone separat ors, bag f illers Et c.

Mixing:

Theory of mixing, solid-solid, solid-liquid and liquid-liquid mixing equipment s.

Filt rat ion and Cent rifugat ion:

Theory of f ilt rat ion, cont inuous and bat ch f ilt ers, f ilt er aids, f ilt er media, indust rial f ilt ers

including f ilt er press, rot ary f ilt er, edge f ilt er, Et c. Fact ors af fect ing f ilt rat ion, f ilt rat ion,

opt imum cleaning cycle in bat ch f ilt ers. Principles of cent rif ugat ion, indust rial cent rifugal f ilt ers,

and cent rif ugal sediment ers.

Cryst allizat ion:

Charact erist ics of cryst als like-purit y, size, shape, geomet ry, habit , f orms size and fact ors

af f ect ing t hem, Solubilit y curves and calculat ion of yields. Mat erial and heat balances around

Swenson Walker Cryst allizer. Supersat urat ion, t heory and it s limit at ions, Nucleat ion mechanisms,

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

cryst al growt h. St udy of various t ypes of Cryst allizers, t anks, agit at ed bat ch, Swenson Walker,

Single vacuum, circulat ing magma and Kryst al Cryst allizer, Caking of cryst als and it s prevent ion.

Numerical problems on yields;

Dehumidif icat ion and Humidit y Cont rol:

Basic concept s and def init ion, wet bulb and adiabat ic sat urat ion t emperat ures, Hygromet ric chart

and measurement of humidit y, applicat ion of humidit y measurement in pharmacy, equipment s f or

dehumidif icat ion operat ions;

Ref rigerat ion and Air Condit ioning:

Principle and applicat ions of ref rigerat ion and air condit ioning;

Mat erial of Const ruct ion :

General st udy of composit ion, corrosion, resist ance, Propert ies and applicat ions of t he mat erials

of const ruct ion wit h special reference t o st ainless st eel and glass.

Mat erial Handling Syst ems:

Liquid handling - Dif f erent t ypes of pumps, Gas handling-Various t ypes of f ans, blowers and

compressors, Solid handling-Bins, Bunkers, Conveyers, Air t ransport .

Corrosion:

Classif icat ion, mechanism of corrosion, f act ors af fect ing, prevent ion and cont rol.

Plant locat ion:

Layout , ut ilit ies and services.

Indust rial Hazards and Safet y Precaut ions:

Mechanical, Chemical, Elect rical, f ire and dust hazards. Indust rial dermat it is, Accident records

Et c.

Aut omat ed Process Cont rol Syst ems:

Process variables, t emperat ure, pressure, flow, level and vacuum and t heir measurement s;

element s of aut omat ic process cont rol and int roduct ion t o aut omat ic process cont rol syst ems;

element s of comput er aided manuf act uring (CAM). React ors and fundament als of react ors design

f or chemical react ions.

Dosages Forms, designing & evaluation

Liquid Dosages Forms:

Int roduct ion, t ypes of addit ives used in f ormulat ions, vehicles, st abilizers, preservat ives,

suspending agent s, emulsif ying agent s, solubilizers, colors, f lavors and ot hers, manuf act uring

packaging, labeling, evaluat ion of clear liquids, suspensions and emulsions of f icial in

pharmacopoeia;

Semisolid Dosage Forms:

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Def init ions, t ypes, mechanisms of drug penet rat ion, f act ors inf luencing penet rat ion, semisolid

bases and t heir select ion. General f ormulat ion of semisolids, clear gels manuf act uring procedure,

evaluat ion and packaging;

Supposit ories:

Ideal requirement s, bases, displacement value, manuf act uring procedure, packaging and

evaluat ion;

Ext ract ion and Galenical Product s:

Principle and met hod of ext ract ion, preparat ion of inf usion, t inct ures, dry and sof t liquid

ext ract s;

Blood Product s and Plasma Subst it ut es:

Collect ion, processing and st orage of whole human blood, concent rat ed human RBCs, dried

human plasma, human f ibrinogen, human t hrombin, human normal immunoglobulin, human

f ibrin, f oam plasma subst it ut es, -ideal requirement s, PVP, dext ran Et c. f or cont rol of blood

pressure as per I. P. ;

Pharmaceut ical Aerosols:

Def init ion, propellant s, general f ormulat ion, manufacturing' and packaging met hods,

pharmaceut ical applicat ions;

Opht halmic Preparat ions:

Requirement s, f ormulat ion, met hods of preparat ion, labeling, cont ainers, evaluat ion;

Cosmet icology and Cosmet ic Preparat ions:

Fundament als of cosmet ic science, st ruct ure and f unct ions of skin and hair. Formulat ion,

preparat ion and packaging of cosmet ics f or skin, hair, dent if rice and manicure preparat ions like

nail polish, nail polish remover, Lipst icks, eye lashes, baby care product s Et c.

Capsules:

Advant ages and disadvant ages of capsule dosage f orm, mat erial f or product ion of hard gelat in

capsules, size of capsules, f ormulat ion, met hod of capsule f illing, sof t gelat in, capsule shell and

capsule cont ent , import ance of base absorpt ion and minimum/ gm f act ors in soft capsules, qualit y

cont rol, st abilit y t est ing and st orage of capsule dosage forms.

Micro-encapsulat ion:

Types of microcapsules, import ance of microencapsulat ion in pharmacy, microencapsulat ion by

phase separat ion, coacervat ion, mult i-orif ice, spray drying, spray congealing, polymerizat ion

complex emulsion, air suspension t echnique, coat ing pan and ot her t echniques, evaluat ion of

micro capsules.

Tablet s:

Advant ages and disadvant ages of t ablet s, Applicat ion of dif f erent t ypes of t ablet s, Formulat ion of

dif f erent t ypes of t ablet s, granulat ion, t echnology on large-scale by various t echniques, diff erent

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

t ypes of t ablet compression machinery and t he equipment s employed, evaluat ion of t ablet s.

Coat ing of Tablet s: Types of coat ing, f ilm f orming mat erials, f ormulat ion of coat ing solut ion,

equipment s f or coat ing, coat ing process, evaluat ion of coat ed t ablet s. St abilit yk inet ics and

qualit y assurance.

Parent eral Product s:

Pre-f ormulat ion f act ors, rout es of administ rat ion, wat er f or inj ect ion, and st erile wat er f or

inj ect ion, pyrogenicit y, non- aqueous vehicles, isot onicit y and met hods of it s adj ust ment ,

Formulat ion det ails, Cont ainers and closures and select ion, labeling; Pre-f illing t reat ment ,

washing of cont ainers and closures, preparat ion of solut ion and suspensions, f illing and closing of

ampoules, vials, inf usion fluids, lyophilizat ion & preparat ion of st erile powders, equipment f or

large scale manuf act ure and evaluat ion of parent eral product s; Asept ic Techniques-source of

cont aminat ion and met hods of prevent ion, Design of asept ic area, Laminar f low bench services

and maint enance. St erilit y t est ing of pharmaceut icals.

Surgical product s:

Def init ion, primary wound dressing, absorbent s, surgical cot t on, surgical gauzes et c., bandages,

adhesive t ape, prot ect ive cellulosic hemost ast ics, off icial dressings, absorbable and non-

absorbable sut ures, ligat ures and cat gut s.

Packaging of Pharmaceut ical Product s:

Packaging component s, t ypes, specif icat ions and met hods of evaluat ion, st abilit y aspect s of

packaging. Packaging equipment s, fact ors influence choice of cont ainers, legal and of f icial

requirement s f or cont ainers, package t est ing.

Designing of dosage f orms:

Pre-f ormulat ion st udies, St udy of physical propert ies of drug like physical f orm, part icle size,

shape, densit y, wet t ing, dielect ric const ant . Solubilit y, dissolut ion and organolept ic propert ies

and t heir ef fect on f ormulat ion, st abilit y and bioavailabilit y. St udy of chemical propert ies of

drugs like hydrolysis, oxidat ion, reduct ion, racemizat ion, polymerizat ion et c. , and t heir inf luence

on f ormulat ion and st abilit y of product s. St udy of pro-drugs in solving problems relat ed t o

st abilit y, bioavailabilit y and elegancy of f ormulat ions. Design, development and process

validat ion met hods f or pharmaceut ical operat ions involved in t he product ion of pharmaceut ical

product s wit h special ref erence t o t ablet s, suspensions. St abilizat ion and st abilit y t est ing prot ocol

f or various pharmaceut ical product s. ICH Guidelines f or st abilit y t est ing of f ormulat ions.

Perf ormance evaluat ion met hods:

In-vit ro dissolut ion st udies f or solid dosage f orms met hods, int erpret at ion of dissolut ion dat a.

Bioavailabilit y st udies and bioavailabilit y t est ing prot ocol and procedures. In vivo met hods of

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

evaluat ion and st at ist ical t reat ment . GMP and qualit y assurance, Qualit y audit . Design,

development , product ion and evaluat ion of cont rolled/ sust ained/ ext ended release f ormulat ions.

Biopharmaceutics & Pharmacokinetics

Int roduct ion t o biopharmaceut ics:

Passage of drugs across biological barrier (passive diff usion, act ive t ransport , facilit at ed diff usion,

ion-pair f ormat ion and pinocyt osis); Fact ors influencing absorpt ion- biological, physico-chemical,

physiological and pharmaceut ical; Drug dist ribut ion in t he body, plasma prot ein binding.

Pharmacokinet ics:

Signif icance of plasma drug concent rat ion measurement . Compart ment model- Def init ion and

Scope. Pharmacokinet ics of drug absorpt ion - Zero order and f irst order absorpt ion rat e const ant

using Wagner-Nel son and residual met hods. Volume of dist ribut ion and dist ribut ion coef f icient .

Compart ment kinet ics- One compart ment and t wo compart ment models. Det erminat ion of

pharmacokinet ic paramet ers from plasma and urine dat a af t er drug administ rat ion by

int ravascul ar and oral rout e. Clearance concept , mechanism of renal clearance, clearance rat io,

det erminat ion of renal clearance. Ext ract ion rat io, hepat ic clearance, biliary excret ion, ext ra-

hepat ic circulat ion. Non-linear pharmacokinet ics wit h special ref erence t o one compart ment

model aft er I.V. drug administ rat ion.

Clinical Pharmacokinet ics:

Def init ion and scope: Dosage adj ust ment in pat ient s wit h and wit hout renal and hepat ic f ailure;

Design of single dose bio-equivalence st udy and relevant st at ist ics; Pharmacokinet ic drug

int eract ions and t heir signif icance in combinat ion t herapy.

Bioavailabilit y and bioequivalence:

Measures of bioavailabilit y, Cmax, t max, Keli and Area Under t he Curve (AUC); Design of single

dose bioequivalence st udy and relevant st at ist ics; Review of regulat ory requirement s f or

conduct ing bioequivalent st udies. Biopharmaceut ical Classif icat ion Syst em (BCS) of drugs.

PHARMACEUTICAL CHEMISTRY

Inorganic pharmaceutical & medicinal chemistry

Import ance of inorganic compounds in pharmacy and medicine;

An out line of met hods of preparat ion, uses, sources of impurit ies, t est s f or purit y and ident it y,

including limit t est s f or iron, arsenic, lead, heavy met als, chloride, sulphat e and special t est s if

any, of t he f ollowing classes of inorganic pharmaceut icals included in Indian Pharmacopoeia:

Gast roint est inal Agent s:

Acidif ying agent s, Ant acids, Prot ect ives and Adsorbent s, Cat hart ics;

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Maj or Int ra- and Ext ra-cellular Elect rolyt es:

Physiological ions. Elect rolyt es used f or replacement t herapy, acid-base balance and combinat ion

t herapy;

Essent ial and Trace Element s:

Transit ion element s and t heir compounds of pharmaceut ical import ance, Iron and haemat inics,

mineral supplement s; Cat ionic and anionic component s of inorganic drugs usef ul f or syst emic

ef fect s;

Topical Agent s:

Prot ect ives, Ast ringent s and Ant i-inf ect ives.

Gases and Vapors:

Oxygen, Anest het ics (inorganic) and Respirat ory st imulant s;

Dent al Product s:

Dent ifrices, Ant i-caries agent s; Complexing and chelat ing agent s used in t herapy;

Miscellaneous Agent s:

Sclerosing agent s, Expect orant s, Emet ics, Inorganic poisons and ant idot es.

Pharmaceut ical Aids Used in Pharmaceut ical Indust ry:

Ant i-oxidant s, Preservat ives, Filt er aids, Adsorbent s, Diluent s, Excipient s, Suspending agent s,

Colorant s;

Acids, Bases and Buff ers:

Buff er equat ions and buff er capacit y in general, buff ers in pharmaceut ical syst ems, preparat ion,

st abilit y, buff ered isot onic solut ions, measurement s of t onicit y, calculat ions and met hods of

adj ust ing isot onicit y.

Inorganic Radiopharmaceut icals:

Nuclear react ion, radioisot opes, radiopharmaceut icals, Nomenclat ure, Met hods of obt aining t heir

st andards and unit s of act ivit y, half-lif e, measurement of act ivit y, clinical applicat ions, dosage,

hazards and precaut ions.

Physical Chemistry and its importance in pharmacy

Import ance of basic fundament als of physical chemist ry in pharmacy:

Behavior of Gases, Kinet ic t heory of gases, deviat ion from ideal behavior and explanat ion.

The Liquid St at e:

Physical propert ies (surf ace t ension, parachor, viscosit y, refract ive index, dipole moment );

Solut ions:

Ideal and real solut ions, solut ions of gases in liquids, colligat ive propert ies, part it ion coeff icient ,

conduct ance and it s measurement , Debye Huckel t heory;

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Thermodynamics:

First , Second and Third laws, Zerot h law, Concept of free energy, ent halpy and ent ropy, absolut e

t emperat ure scale;

Thermochemical equat ions; Phase rule; Adsorpt ion:

Freudlich and Gibbs adsorpt ion, isot herms, Langmuir’ s t heory of adsorpt ion.

Phot ochemist ry:

Consequences of light absorpt ion, Jabolenski diagram, Quant um ef f iciency;

Chemical Kinet ics:

Zero, First and Second order react ions, complex react ions, t heories of react ion kinet ics,

charact erist ics of homogeneous and het erogeneous cat alysis, acid base and enzyme cat alysis;

Quant um Mechanics :

Post ulat es of quant um mechanics, operat ors in quant um mechanics, t he Schrodinger wave

equat ion.

Organic Chemistry and its importance in pharmacy

Import ance of f undament als of organic chemist ry in pharmaceut ical sciences; St ruct ure and Propert ies:

At omic st ruct ure, At omic orbit als, Molecular orbit al t heory, wave equat ion, Molecular orbit als,

Bonding and Ant i-bonding orbit als, Covalent bond, Hybrid orbit als, Int ramolecular f orces, Bond

dissociat ion energy, Polarit y of bonds, Polarit y of molecules, St ruct ure and physical propert ies,

Int ermolecular f orces, Acids and bases;

St ereochemist ry:

Nomenclat ure, isomerism, st ereoisomerism, conf ormat ional and conf igurat ional isomerism,

opt ical act ivit y, specif icat ion of conf igurat ion, React ions involving st ereoisomers, chiralit y,

conf ormat ions;

St ereoselect ive and st ereospecif ic react ions; St ruct ure, Nomenclat ure, Preparat ion and React ions of :

Alkanes, Alkenes, Alkynes, Cyclic analogs, Dienes, Benzene, Polynuclear aromat ic compounds,

Arenes, Alkyl halides, Alcohols, Et hers, Epoxides, Amines, Phenols, Aldehydes and ket ones,

Carboxylic acids, Funct ional derivat ives of ' carboxylic acids, a,ß-Unsat urat ed carbonyl

compounds, React ive int ermediat es- carbocat ions, carbanions, carbenes and nit renes;

Nucleophilic and Elect rophilic Aromat ic Subst it ut ion React ions:

React ivit y and orient at ion;

Elect rophilic and Nucleophilic Addit ion React ions; Rearrangement s

(Beckman, Hoff man, Benzilic acid, pinacole-pinacolone and Bayer-Villager).

Eliminat ion react ions; Conservat ion of Orbit al Symmet ry and Rules:

Elect rocyclic, Cycloaddit ion and Sigmat ropic react ions;

Neighboring group ef f ect s; Cat alysis by t ransit ion met al complexes; Het erocyclic Compounds:

11
PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Nomenclat ure, preparat ion, propert ies and react ions of 3, 4, 5, 6 & 7-membered het erocycles

wit h one or t wo het eroat oms like 0, N, S. Chemist ry of lipids, Carbohydrat es and Prot eins.

Biochemistry

Biochemist ry in pharmaceut ical sciences:

The concept of free energy, Det erminat ion of change in free energy - from equilibrium const ant

and reduct ion pot ent ial, bioenerget ics, product ion of ATP and it s biological signif icance;

Enzymes:

Nomenclat ure, enzyme kinet ics and t heir mechanism of act ion, mechanism of inhibit ion, enzymes

and iso-enzymes in clinical diagnosis.

Co-enzymes:

Vit amins as co-enzymes and t heir signif icance. Met als as cof act ors and t heir signif icance;

Carbohydrat e Met abolism: Conversion of polysaccharides t o glucose-1-phosphat e, Glycolysis,

f erment at ion and t heir regulat ion, Gluconeogenesis and glycogenolysis, Met abolism of galact ose

and galact osemia, Role of sugar nucleot ides in biosynt hesis, and Pent ose phosphat e pat hway;

The Cit ric Acid Cycle:

Signif icance, react ions and energet ics of t he cycle, Amphibolic role of t he cycle, and Glyoxalic

acid cycle;

Lipids Met abolism :

Oxidat ion of f at t y acids, ß-oxidat ion & energet ics, biosynt hesis of ket one bodies and t heir

ut ilizat ion, biosynt hesis of sat urat ed and unsat urat ed f at t y acids, Cont rol of lipid met abolism,

Essent ial f at t y acids & eicosanoids (prost aglandins, t hromboxanes and leukot rienes),

phospholipids, and sphingolipids, Biosynt hesis of eicosanoids, cholest erol, androgens,

progest erone, est rogens cort icost eroids and bile acids.

Biological Oxidat ion:

Redox-pot ent ial, enzymes and co-enzymes involved in oxidat ion reduct ion & it s cont rol, The

respirat ory chain, it s role in energy capt ure and it s cont rol, energet ics of oxidat ive

phosphorylat ion. Inhibit ors of respirat ory chain and oxidat ive phosphorylat ion, Mechanism of

oxidat ive phosphorylat ion.

Met abolism of ammonia and nit rogen cont aining monomers:

Nit rogen balance, Biosynt hesis of amino acids, Cat abolism of amino acids, Conversion of amino

acids t o specialized product s, Assimilat ion of ammonia, Urea cycle, met abolic disorders of urea

cycle, Met abolism of sulphur cont aining amino acids.

Purine biosynt hesis:

Purine nucleot ide int er-conversions.

Pyrimidine biosynt hesis and f ormat ion of deoxyribounucleot ides.

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Biosynt hesis of Nucleic Acids:

Brief int roduct ion of genet ic organizat ion of t he mammalian genome, alt erat ion and

rearrangement s of genet ic mat erial, Biosynt hesis of DNA and it s replicat ions.

Mut at ion:

Physical & chemical mut agenesis/ carcinogenesis, DNA repair mechanism. Biosynt hesis of RNA;

Genet ic Code and Prot ein Synt hesis:

Genet ic code, Component s of prot ein synt hesis and Inhibit ion of prot ein synt hesis.

Medicinal Chemistry

Basic Principles:

Physico-chemical and st ereoisomeric (Opt ical, geomet rical) aspect s of drug molecules and

biological act ion, Bioisost erism, Drug-recept or int eract ions including t ransduct ion mechanisms;

Drug met abolism and Concept of Prodrugs; Principles of Drug Design (Theoret ical Aspect s):

Tradit ional analog and mechanism based approaches, QSAR approaches, Applicat ions of quant um

mechanics, Comput er Aided Drug Designing (CADD) and molecular modeling.

Synt het ic Procedures, Mode of Act ion, Uses, St ruct ure Act ivit y Relat ionships including Physicochemical

Propert ies of t he Following Classes of Drugs:

Drugs act ing at synapt ic and neuro-ef f ect or j unct ion sit es: Cholinergics, ant i-cholinergics and

cholinest erase inhibit ors, Adrenergic drugs, Ant ispasmodic and ant i-ulcer drugs, Local

Anest het ics, Neuromuscular blocking agent s.

Aut acoids:

Ant ihist amines, Eicosanoids, Analgesic-ant ipyret ics, Ant i-inf lammat ory (non-st eroidal) agent s.

St eroidal Drugs:

St eroidal nomenclat ure (IUPAC) and st ereochemist ry, Androgens and anabolic agent s, Est rogens

and Progest at ional agent s, Oral cont racept ives, Adrenocort icoids;

Drugs act ing on t he cent ral nervous syst em:

General Anest het ics, Hypnot ics and Sedat ives, Ant iconvulsant s, Ant i-Parkinsonian drugs,

Psychopharmacological agent s (Neurolept ics, Ant i-depressant s, Anxiolyt ics), Opioid analgesics,

Ant i-t ussives, CNS st imulant s.

Diuret ics; Cardiovascular drugs:

Ant i-hypert ensives, Ant i-arryt hmic agent s, ant i-anginal agent s, Cardiot onics, Ant i-hyperlipedemic

agent s, Ant icoagulant s and Ant i-plat elet drugs.

Thyroid and Ant i t hyroid drugs; Insulin and oral hypoglycemic agent s:

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Chemot herapeut ic Agent s used in bact erial, fungal, viral, prot ozoal, parasit ic and ot her

inf ect ions, Ant ibiot ics: ß-Lact am, macrolides, t et racyclines, aminoglycosides, polypept ide

ant ibiot ics, fluoroquinolones,

Ant i-met abolit es (including sulf onamides); Ant i-neoplast ic agent s; Ant i-viral agent s (including ant i–HIV);

Immunosuppressives and immunost imulant s; Diagnost ic agent s; Pharmaceut ical Aids.

Microbial Transf ormat ions:

Int roduct ion, t ypes of react ions mediat ed by micro-organisms, design of biot ransf ormat ion

processes, select ion of organisms, biot ransf ormat ion process and it s improvement s wit h special

reference t o st eroids.

Enzyme Immobilizat ion:

Techniques of immobilizat ion, f act ors aff ect ing enzyme kinet ics, St udy of enzymes such as

hyaluronidase, penicillinase, st rept okinase, amylases and prot eases, Immobilizat ion of bact eria

and plant cells.

Pharmaceutical Analysis

Dif ferent t echniques of pharmaceut ical analysis, Preliminaries and def init ions:

Signif icant f igures, Rules f or ret aining signif icant digit s, Types of errors, Mean deviat ion, St andard

deviat ion, St at ist ical t reat ment of small dat a set s, Select ion of sample, Precision and accuracy.

Fundament als of volumet ric analysis:

Met hods of expressing concent rat ion, primary and secondary st andards:

Acid Base Tit rat ions:

Acid base concept s, Role of solvent s, Relat ive st rengt hs of acids and bases, Ionizat ion, Law of

mass act ion, Common ion ef fect , Ionic product of wat er, pH, Hydrolysis of salt s, Henderson-

Hasselbach equat ion, Buf fer solut ions, Neut ralizat ion curves, Acid-base indicat ors, Theory of

indicat ors, Choice of indicat ors, Mixed indicat ors, Polyprot ic syst ems, Polyamine and amino acid

syst ems, Amino acid t it rat ions.

Oxidat ion Reduct ion Tit rat ions:

Concept s of oxidat ion and reduct ion, Redox react ions, St rengt hs and equivalent weight s of

oxidizing and reducing agent s, Theory of redox t it rat ions, Redox indicat ors, Cell represent at ions,

Measurement of elect rode pot ent ial, Oxidat ion-reduct ion curves, Iodimet ry and Iodomet ry,

Tit rat ions involving cerric ammonium sulphat e, pot assium iodat e, pot assium bromat e, pot assium

permanganat e; t it anous chloride, st annous chloride and Sodium 2, 6-dichlorophenolindophenol.

Precipit at ion Tit rat ions:

Precipit at ion react ions, Solubilit y product , Ef fect of acids, t emperat ure and solvent upon t he

solubilit y of a precipit at e, Argent omet ric t it rat ions and t it rat ions involving ammonium or

pot assium t hiocyanat e, mercuric nit rat e, and barium sulphat e, indicat ors, Met hods of end point

det erminat ion (GayLussac met hod, Mohr’ s met hod, Volhard's met hod and Faj an's met hod).

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Gravimet ric Analysis:

Precipit at ion t echniques, The colloidal st at e, Supersat urat ion, Co-precipit at ion, Post -

precipit at ion, Digest ion, washing of t he precipit at e, Filt rat ion, Filt er papers and crucibles,

Ignit ion, Thermogravimet ric curves, Specif ic examples like barium sulphat e, aluminium as

aluminium oxide, calcium as calcium oxalat e and magnesium as magnesium pyrophosphat e,

Organic precipit ant s.

Non-aqueous t it rat ions:

Acidic and basic drugs, Solvent s used, Indicat ors.

Complexomet ric t it rat ions:

Complexing agent s used as t it rant s, Indicat ors, Masking and demasking;

Miscellaneous Met hods of Analysis:

Diazot izat ion t it rat ions, Kj eldahl met hod of nit rogen est imat ion, Karl-Fischer aquamet ry, Oxygen

f lask combust ion met hod, Gasomet ry.

Ext ract ion procedures including separat ion of drugs from excipient s; Pot ent iomet ry:

St andard redox pot ent ial, Nernst equat ion, Half-cell pot ent ial, St andard and indicat ing

elect rodes, pot ent iomet ric t it rat ions;

Conduct omet ry:

Specif ic and equivalent conduct ance, conduct omet ric t it rat ions.

Coulomet ry:

Coulomb’ s law, Coulomet ric t it rat ions at f ixed pot ent ial/ current .

Polarography:

Decomposit ion pot ent ial, Half-wave pot ent ial, Dif f ision/ migrat ion/ migrat ion current , Ilkovic

equat ion, Cat hodic/ anodic polarography, Dropping mercury elect rode, Graphit e elect rode,

Organic polarography.

Amperomet ry:

Rot at ing plat inum elect rode, Amperomet ric t it rat ions.

Chromat ography:

Theory of chromat ography, plat e t heory, Fact ors af fect ing resolut ion, van Deemt er equat ion. The

f ollowing chromat ographic t echniques (including inst rument at ion) wit h relevant examples of

Pharmacopoeial product s: TLC, HPLC, GLC, HPTLC, Paper Chromat ography and Column

Chromat ography.

The Theoret ical Aspect s, Basic Inst rument at ion, Element s of Int erpret at ion of Spect ra, and Applicat ions

(quant it at ive and qualit at ive) of t he Following Analyt ical Techniques:

Ult raviolet and visible spect rophot omet ry, Fluorimet ry, Inf rared spect rophot omet ry, Nuclear

Magnet ic Resonance spect roscopy [ prot on t echnique only] , Mass Spect romet ry (EI & CI only),

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Flame Phot omet ry, At omic Absorpt ion Spect roscopy, X-ray Diff ract ion Analysis,

Radioimmunoassay.

Qualit y assurance:

GLP, ISO 9000, TQM, Qualit y Review and Qualit y document at ion, Regulat ory cont rol, regulat ory

drug analysis, int erpret at ion of analyt ical dat a, Validat ion, qualit y audit : qualit y of equipment ,

validat ion of equipment , validat ion of analyt ical procedures.

PHARMACOLOGY

Pat hophysiology of common diseases; Basic Principles of Cell Inj ury and Adapt at ions:

Causes of Cellular inj ury, pat hogenesis, morphology of cell inj ury, adapt at ions and cell deat h.

Basic Mechanisms involved in t he process of inf lammat ion and repair:

Vascular and cellular event s of acut e inflammat ion, chemical mediat ors of inf lammat ion,

pat hogenesis of chronic inf lammat ion, brief out line of t he process of repair.

Immunopat hophysiology:

T and B cells, MHC prot eins, ant igen present ing cells, immune t olerance, pat hogenesis of

hypersensit ivit y react ions, aut oimmune diseases, AIDS, Amyloidosis.

Pat hophysiology of Common Diseases:

Ast hma, diabet es, rheumat oid art hrit is, gout , ulcerat ive colit is, neoplasia, psychosis, depression,

mania, epilepsy, acut e and chronic renal failure, hypert ension, angina, congest ive heart f ailure,

at herosclerosis, myocardial inf arct ion, congest ive heart failure, pept ic ulcer, anemias, hepat ic

disorders, t uberculosis, urinary t ract infect ions and sexually t ransmit t ed diseases. Wherever

applicable t he molecular basis should be discussed.

Fundament als of general pharmacology:

Dosage f orms and rout es of administ rat ion, mechanism of act ion, combined eff ect of drugs,

f act ors modif ying drug act ion, t olerance and dependence; Pharmacogenet ics; Principles of Basic

and Clinical pharmacokinet ics, absorpt ion, Dist ribut ion, Met abolism and Excret ion of drugs,

Adverse Drug React ions; Bioassay of Drugs and Biological St andardizat ion; Discovery and

development of new drugs, Bioavailabilit y and bioequivalence st udies;

Pharmacology of Peripheral Nervous Syst em:

Neurohumoral t ransmission (aut onomic and somat ic), Parasympat homimet ics,

Parasympat holyt ics, Sympat homimet ics, Adrenergic recept or and neuron blocking agent s,

Ganglion st imulant s and blocking agent s, Neuromuscular blocking Agent s, Local anest het ic

Agent s.

Pharmacology of Cent ral Nervous Syst em:

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Neurohumoral t ransmission in t he C.N. S. , General Anest het ics, Alcohols and disulf iram, Sedat ives,

Hypnot ics, Ant i-anxiet y agent s and Cent rally act ing muscle relaxant s, Psychopharmacological

agent s (ant i-psychot ics), ant i-maniacs, and hallucinogens, Ant idepressant s, Ant i-epilept ics drugs,

Ant i-Parkinsonian drugs, Analgesics, Ant ipyret ics, Narcot ic analgesics and ant agonist s, C. N. S.

st imulant s, Drug Addict ion and Drug Abuse.

Pharmacology of Cardiovascular Syst em:

Drugs used in t he management of congest ive cardiac f ailure, Ant ihypert ensive drugs, Ant i-anginal

and Vasodilat or drugs, including calcium channel blockers and bet a adrenergic ant agonist s, Ant i-

arrhyt hmic drugs, Ant i-hyperlipedemic drugs, Drugs used in t he t herapy of shock.

Drugs Act ing on t he Hemopoiet ic Syst em:

Hemat inics, Ant icoagulant s, Vit amin K and hemost at ic agent s, Fibrinolyt ic and ant i-plat elet

drugs, Blood and plasma volume expanders.

Drugs act ing on urinary syst em:

Fluid and elect rolyt e balance, Diuret ics.

Aut acoids:

Hist amine, Ant ihist aminic drugs, 5-HT- it s agonist s and ant agonist s, Prost aglandins, t hromboxanes

and leukot rienes, Angiot ensin, Bradykinin and Subst ance P and ot her vasoact ive pept ides, non-

st eroidal ant i-inf lammat ory and ant i-gout agent s.

Drugs Act ing on t he Respirat ory Syst em:

Ant i-ast hmat ic drugs including bronchodilat ors, Ant i-t ussives and expect orant s, Respirat ory

st imulant s.

Drugs act ing on t he Gast roint est inal Tract :

Ant acids, Ant i-secret ory and Ant i-ulcer drugs, Laxat ives and ant i-diarrhoeal drugs, Appet it e

St imulant s and Suppressant s, Emet ics and ant i-emet ics, Miscellaneous: Carminat ives, demulcent s,

prot ect ives, adsorbent s, ast ringent s, digest ant s, enzymes and mucolyt ics.

Pharmacology of Endocrine Syst em:

Hypot halamic and pit uit ary hormones, Thyroid hormones and ant i-t hyroid drugs, parat hormone,

calcit onin and Vit amin D, Insulin, glucagons, incret ins, oral hypoglycemic agent s and insulin

analogs, ACTH and cort icost eroids, Androgens and anabolic st eroids, Est rogens, progest erone and

oral cont racept ives, Drugs act ing on t he ut erus.

Chemot herapy:

General Principles of Chemot herapy, Bact erial resist ance; Sulf onamides and cot rimoxazole,

Ant ibiot ics- Penicillins, Cephalosporins, Aminoglycosides, Chloramphenicol, Macrolides,

Tet racyclines, Quinolones, fluoroquinolones and Miscellaneous ant ibiot ics; Chemot herapy of

t uberculosis, leprosy, fungal diseases, viral diseases, HIV and AIDS, urinary t ract infect ions and

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

sexually t ransmit t ed diseases, malaria, amoebiasis and ot her prot ozoal infect ions and

Ant helment ics. Chemot herapy of malignancy and immunosuppressive agent s.

Principles of Toxicology:

Def init ion of poison, general principles of t reat ment of poisoning wit h part icular reference t o

barbit urat es, opioids, organophosphorous and at ropine poisoning, Heavy met als and heavy met al

ant agonist s.

Basic Concept s of Pharmacot herapy:

Clinical Pharmacokinet ics and individualizat ion of Drug t herapy, Drug delivery syst ems and t heir

Biopharmaceut ic s & Therapeut ic considerat ions, Drugs used during inf ancy and in t he elderly

persons (Pediat rics & Geriat rics), Drugs used during pregnancy, Drug induced diseases, The basics

of drug int eract ions, General principles of clinical t oxicology, Common clinical laborat ory t est s

and t heir int erpret at ion.

Import ant Disorders of Organs, Syst ems and t heir Management :

Cardio-vascular disorders- Hypert ension, Congest ive heart f ailure, Angina, Acut e myocardial

inf arct ion, Cardiac arrhyt hmias.

CNS Disorders:

Epilepsy, Parkinsonism, Schizophrenia, Depression.

Respirat ory disease-

Ast hma.

Gast roint est inal Disorders-

Pept ic ulcer, Ulcerat ive colit is, Hepat it is, Cirrhosis.

Endocrine Disorders-

Diabet es mellit us and Thyroid disorders.

Inf ect ious Diseases-

Tuberculosis, Urinary t ract infect ions, Ent eric inf ect ions, Upper respirat ory inf ect ions.

Hemat opoiet ic Disorders- Anemias,

Joint and Connect ive t issue disorders-

Rheumat ic diseases, Gout and Hyperuricemia.

Neoplast ic Diseases-

Acut e Leukaemias, Hodgkin's disease. Therapeut ic Drug Monit oring, Concept of Essent ial Drugs

and Rat ional Drug use.

PHARMACOGNOSY

Sources of Drugs:

Biological, marine, mineral and plant t issue cult ures as sources of drugs;

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Classif icat ion of Drugs:

Morphological, t axonomical, chemical and pharmacological classif icat ion of drugs;

St udy of medicinally import ant plant s belonging t o t he f amilies wit h special ref erence t o:

Apocynacae, Solanaceae, Rut aceae, Umbellif erae, Leguminosae, Rubiaceae, Liliaceae, Graminae,

Labiat ae, Cruciferae, Papaveraceae.

Cult ivat ion, Collect ion, Processing and St orage of Crude Drugs:

Fact ors inf luencing cult ivat ion of medicinal plant s, Types of soils and fert ilizers of common use.

Pest management and nat ural pest cont rol agent s, Plant hormones and t heir applicat ions,

Polyploidy, mut at ion and hybridizat ion wit h ref erence t o medicinal plant s.

Qualit y Cont rol of Crude Drugs:

Adult erat ion of crude drugs and t heir det ect ion by organolept ic, microscopic, physical, chemical

and biological met hods and propert ies.

Int roduct ion t o Act ive Const it uent s of Drugs:

Their isolat ion, classif icat ion and propert ies.

Systematic pharmacognostic study of the followings:

CARBOHYDRATES and derived product s:

agar, guar gum acacia, Honey, Isabagol, pect in, St arch, st erculia and Tragacant h.

Lipids:

Bees wax, Cast or oil, Cocoa but t er, Codliver oil, Hydnocarpus oil, Kokum but t er, Lard, Linseed

oil, Rice Bran oil, Shark liver oil and Wool f at .

RESINS:

St udy of Drugs Cont aining Resins and Resin Combinat ions like Colophony, podophyllum, j alap,

cannabis, capsicum, myrrh, asaf oet ida, balsam of Tolu, balsam of Peru, benzoin, t urmeric,

ginger.

TANNINS:

St udy of t annins and t annin cont aining drugs like Gambier, black cat echu, gall and myrobalan.

VOLATILE OILS:

General met hods of obt aining volat ile oils from plant s, St udy of volat ile oils of Ment ha,

Coriander, Cinnamon, Cassia, Lemon peel, Orange peel, Lemon grass, Cit ronella, Caraway, Dill,

Spearmint , Clove, Fennel, Nut meg, Eucalypt us, Chenopodium, Cardamom, Valerian, Musk,

Palmarosa, Gault heria, Sandal wood;

Phyt ochemical Screening:

Preparat ion of ext ract s, Screening of alkaloids, saponins, cardenolides and buf adienolides,

f lavonoids and leucoant hocyanidins, t annins and polyphenols, ant hraquinones, cynogenet ic

glycosides, amino acids in plant ext ract s.

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

FIBERS:

St udy of f ibers used in pharmacy such as cot t on, silk, wool, nylon, glass-wool, polyest er and

asbest os.

Study of the biological sources, cultivation, collection, commercial varieties, chemical constituents,

substitutes, adulterants, uses, diagnostic macroscopic and microscopic features and specific chemical

tests of following groups of drugs.

GLYCOSIDE CONTAINING DRUGS:

Saponins :

Liquorice, ginseng, dioscorea, sarsaparilla, and senega.

Cardioact ive glycosides:

Digit alis, squill, st rophant hus and t hevet ia,

Ant hraquinone cat hart ics:

Aloe, senna, rhubarb and cascara,

Ot hers:

Psoralea, gent ian, saf fron, chirat a, quassia.

ALKALOID CONTAINING DRUGS:

Pyridine-piperidine:

Tobacco, areca and lobelia.

Tropane:

Belladonna, hyoscyamus, dat ura, duboisia, coca and wit hania.

Quinoline and Isoquinoline:

Cinchona, ipecac, opium.

Indole:

Ergot , rauwolf ia, cat harant hus, nux-vomica and physost igma.

Imidazole:

Pilocarpus.

St eroidal:

Verat rum and kurchi.

Alkaloidal Amine:

Ephedra and colchicum.

Glycoalkaloid:

Solanum.

Purines:

Cof f ee, t ea and cola. Biological sources, preparat ion, ident if icat ion t est s and uses of t he

f ollowing enzymes: Diast ase, papain, pepsin, t rypsin, pancreat in.

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PHARMAROCKS GPAT SUCCESS TEST SERIES 2020: THE WAY OF SUCCESS GPAT 2020 SYLLABUS

Studies of Traditional Drugs:

Common vernacular names, bot anical sources, morphology, chemical nat ure of chief const it uent s,

pharmacology, cat egories and common uses and market ed f ormulat ions of f ollowing indigenous

drugs: Amla, Kant kari, Sat avari, Tylophora, Bhilawa, Kalij iri, Bach, Rasna, Punamava, Chit rack,

Apamarg, Gokhru, Shankhapushpi, Brahmi, Adusa, At j una, Ashoka, Met hi, Lahsun, Palash, Guggal,

Gymnema, Shilaj it , Nagarmot ha and Neem. The holist ic concept of drug administ rat ion in

t radit ional syst ems of medicine. Int roduct ion t o ayurvedic preparat ions like Arisht as, Asvas,

Gut ikas, Tailas, Chumas, Lehyas and Bhasmas.

General Techniques of Biosynthetic Studies and Basic Metabolic Pathways/ Biogenesis:

Brief int roduct ion t o biogenesis of secondary met abolit es of pharmaceut ical import ance.

Terpenes:

monot erpenes, sesquit erpenes, dit erpenes, and t rit erpenoids.

Carot enoids:

a-carot enoids, ß-carot enes, vit amin A, Xant hophylls of medicinal import ance.

Glycosides:

Digit oxin, digoxin, hecogenin, sennosides, diosgenin and sarasapogenin.

Alkaloids:

At ropine and relat ed compounds, Quinine, Reserpine, Morphine, Papaverine, Ephedrine, Ergot

and Vinca alkaloids.

Lignans, quassanoids and f lavonoids. Role of plant -based drugs on Nat ional economy:

A brief account of plant based indust ries and inst it ut ions involved in work on medicinal and

aromat ic plant s in India. Ut ilizat ion and product ion of phyt o-const it uent s such as quinine, calcium

sennosides, podophyllot oxin, diosgenin, solasodine, and t ropane alkaloids. Ut ilizat ion of aromat ic

plant s and derived product s wit h special ref erence t o sandalwood oil, ment ha oil, lemon grass oil,

vet iver oil, geranium oil and eucalypt us oil. World-wide t rade in medicinal plant s and derived

product s wit h special ref erence t o diosgenin (disocorea), t axol (Taxussps) digit alis, t ropane

alkaloid cont aining plant s, Papain, cinchona, Ipecac, Liquorice, Ginseng, Aloe, Valerian, Rauwolf ia

and plant s cont aining laxat ives. Plant bit t ers and sweet eners.

Plant Tissue Cult ure:

Hist orical development of plant t issue cult ure, t ypes of cult ures, nut rit ional requirement s,

growt h and t heir maint enance. Applicat ions of plant t issue cult ure in pharmacognosy.

Marine pharmacognosy:

Novel medicinal agent s from marine sources.

Nat ural allergens and phot osensit izing agent s and f ungal t oxins. Herbs as healt h f oods. Herbal cosmet ics.

St andardizat ion and qualit y cont rol of herbal drugs, WHO guidelines f or t he st andardizat ion of herbal drugs.

21
 GPAT 2020
BOOKLET

PART II
EXPERT GUIDANCE
M R. AM AR M . RAVAL (M .PHARM )
PHARM AROCKS GPAT SUCCESS SERIES-2020: THE WAY OF SUCCESS EXPERT GUIDANCE

GPAT & NIPER PREPARATION PLAN

When you start preparation of GPAT and NIPER. First of all give importance to the GPAT,
because the preparation strategy is different for GPAT and NIPER. Whereas GPAT concentrate
on subject knowledge deeply and it is somewhat time taking to answer the questions when
compare to the NIPER in which concentrate only on basics of subject especially in organic and
stereo chemistry and analytical chemistry. And also when you qualified in GPAT then only
you will be eligible for NIPER.
First divide all subjects from simple to difficulty and according to their weightage in entrance
exam. According to my opinion I will give an idea First start with order
1. Pharmacognosy
2. Pharmacology
3. Analysis
4. Pharmaceutical calculations
5. Pharmaceutical Jurisprudence
6. Biochemistry, Microbilogy, Biotechnology
7. Pharmaceutics- physical pharmacy
Unit operations
Bio pharmaceutics
Dispensing and clinical pharmacy
8. Medicinal Chemistry
(If u can study comparatively with pharmacology otherwise give last preference.
Follow this order I think it is easy for you.)
 When you start preparation with pharmacognosy. First you should be concentrate on
lecturing of lecturer. It helps to remember easy and can’t easily forget.
 Prepare class running notes by simultaneous listening and note the important points and
differences and note down the doubts separately and ask later class finishing to your
lecturer.
 After Class College time it is better to revise on class notes and note the bits which are
asked in previous exams.
 Before class starting once you check and observe the notes of yesterday.
 For every subject these steps are must be do then there is no tough feel in your
preparation. Otherwise somewhat difficult you feel.

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Important topics for GPAT must study topics from each core subject for GPAT

As we all know that the standard of GPAT exam has been increased many folds from last few
years. So, now t requires lot of hard work and determination to go past through the hurdle of
GPAT. The best thing about GPAT is that as now from this year total number of qualified
students has been reduced to around three thousand only so the qualified students will get surely
get admissions in the most premier pharmaceutical institutions of the nation.

So, if you are also a GPAT aspirant then don’t be disheartened with the decreased number
seats, instead work with double zeal to qualify GPAT with flying colors. The most important
thing to require about the GPAT is that along with hard work one must also clear about the
topics to be covered for GPAT preparation. In this article I am discussing the 5 most important
topics of each core subject which must be studied for the GPAT preparation by every aspirant.
So, now let us have a glance on each important topic one by one starting from the
Pharmaceutics.

IMPORTANT TOPICS OF PHARMACEUTICS FOR GPAT

Pharmaceutics is the indispensable subject for those who wish to qualify GPAT with flying
colors. Although one should study whole pharmaceutics thoroughly but if I am asked to give
the most important topics, then I will recommend below 5 topics. Let me explain each topic
one by one and explain.

(A) Tablet formulation-

Formulation of a tablet is the very first thing that a GPAT aspirant should start with the
pharmaceutics. There are questions from this topic every year in the GPAT exam. In the
formulation, one should study about different components used in the tablet formulation. One
should also ponder on the different interactions among the different components of a tablet.

(B) Sterilization-
Sterilization is another topic for the GPAT. Every year I clearly 2-3 questions in the GPAT
exam from sterilization. One should study thoroughly different technique of sterilization along
with their mechanism. Microbial organisms used for the assay of sterilization are also important
from the GPAT point of view.

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(C) Numerical
Numerical is the area where most of the pharma students lack. But trust me this is the only area
which can provide you edge over the other students. There are around 5-8 questions every year
in the GPAT which tests the numerical ability of the student. Questions are generally asked
from biopharmaceutics, dilutions, freezing point etc.

(D) Suspension & Emulsion formulation-

Formulation of suspensions and emulsions also do play an important role in the GPAT
preparation. Due weightage is given to the surfactants and HLB scale in the GPAT exam. One
should also study the evaluation of suspension and emulsions in detail.

(E) Rheology-
Rheology is also very scoring portion for the preparation of GPAT. In rheology, one should
study types of flow with examples, different types of mills, angle of repose, Carr’s index,
Hausner’s ratio etc.

Important topics of pharmacognosy for GPAT

Those who prepare for the GPAT know the importance of studying pharmacognosy to qualify
GPAT. Pharmacognosy can be a deciding factor between the qualified and non-qualified
students. Pharmacognosy is considered as the life line for the GPAT aspirants as it is the most
scoring subject in the GPAT. Important topics for the GPAT include:
(A) Phytochemical Screening-
In each paper of GPAT irrespective of the year, I always find a question or two on the
phytochemical screening. So, if studying two or three pages of phytochemical screening can
earn you more than 5 marks in the GPAT then I don’t think that it’s a deal of loss.
Phytochemical screening is best given in the CK Kokate’s book pharmacognosy.
(B) Analytical Pharmacognosy-
Analytical Pharmacognosy is the other topic which holds high weight age in the GPAT exam.
One should different stomata’s, trichomes, moisture content, WHO guidelines in the analytical
pharmacognosy. For this topic also CK Kokate is the best for GPAT purpose.
(C) General Pharmacognosy-
You must be wondering or confused that what should be studied by the students in general
pharmacognosy? Let me explain it; in general pharmacognosy one should study thoroughly

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about general description, classification etc. of glycosides, alkaloids, terpenoids etc. In other
words, one should study general pharmacognosy of glycosides, alkaloids and terpenoids.
(D) Biological source of all drugs-
Yes! You have read it right that for GPAT you have to learn the biological source of all the
drugs along with their families. You will definitely find question on the biological sources in
the GPAT exam. To avoid last minute confusion, I highly recommend that one should learn 10
new biological sources of drugs daily and revise the previous ones.
(E) Detailed study of selected drugs-
From the papers of last ten years, I have come to know that there are certain fixed drugs which
have very high probability of asking in the GPAT exam. There are nearly about 30 such potent
drugs with the point of view of GPAT. I will give details about them in my next article. Till
then you can start your preparation with the detailed study of Digitalis, Senna and Atropa.

IMPORTANT TOPICS OF PHARMACOLOGY FOR GPAT

(A) Receptors
This topic covers minimum 1-2 questions of the GPAT question paper every year. Students
preparing for the GPAT must study different types of receptors along with their mechanism of
actions. Questions on the receptors seem tricky in the GPAT exam but if this chapter is studied
thoroughly then I am sure one can easily solve these questions. Beside from the GPAT, this is
also a very interesting and knowledge worthy topic to read for a student of pharmacology.

(B) Autonomic nervous system

Autonomic nervous system or ANS is of prime importance while studying for the GPAT. Every
year ANS has 2-3 questions in the question paper of GPAT. In ANS, beta-blockers should be
given utmost weightage while preparing the topic for GPAT. Different effect of sympathetic
and parasympathetic nervous system should also be studied carefully while preparing for the
GPAT exam.
(C) Cardiovascular system
Next most important topic for the GPAT is cardiovascular system. This is also a very broad
topic including cardiac agents, antihypertensive drugs, antiarrhythmic drugs and anti-lipid emic
drugs. All these topics are of equal importance but cardiac glycosides can be given little extra
importance. These drugs should be studied for their mechanism of action, drug interactions,
side effects and main uses.

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(D) Anti-epileptic drugs

Epilepsy is also an important topic with respect to GPAT. The best book to study epilepsy and
drugs used to treat is KD Tripathi Essential of pharmacology. In the anti-epilepsy along with
mechanism and side effect of each class of anti-epileptic drug one must study the specific drug
used to treat specific type of seizure.
(E) Drugs used to treat cancer-
Cancer is also a hot topic with the point of GPAT exam. Classification of anti-cancer drugs
along with mechanism of action should be thoroughly studied as every year there is a question
on the anti-cancer drugs. Along with this, we should also focus his studies on the newer agents
used for the treatment of cancer.

IMPORTANT TOPICS OF PHARMACEUTICAL CHEMISTRY FOR GPAT

From last few years trend has been made that questions asked in the GPAT has been shifted
from the medicinal chemistry to core organic chemistry. There are quite good number of
questions from the pharmaceutical chemistry portion of the syllabus. The questions asked in
the pharmaceutical chemistry are very basic and test the knowledge of the student. Important
questions of pharmaceutical chemistry include:
(A) Important name reactions-
Now from last few years, more number of direct questions has been asked from the name
reactions. If one can observe then he will find that there hardly 20 important name reactions to
study. If one can study these name reactions with mechanisms then definitely he will be able
to solve 2-3 questions in the GPAT. Important name reactions for GPAT include: Aldol
condensation, Cannizaro reaction, SN1 and SN2 reactions, Rimer-tieman reaction etc.
(B) Basic reaction mechanism
Next important topic to cover for the GPAT in pharmaceutical chemistry is basic reaction
mechanisms. One should thoroughly study electrophilic and nucleophilic substitution and
addition reactions. Whole organic chemistry revolves around these four basic types of reaction
mechanisms. So, if one can command over these four reaction mechanisms then he can answer
many questions of organic chemistry.
(C) Basics of organic chemistry
Beside from name reactions and reaction mechanisms, there are still lots of things to be
considered in the organic chemistry. These basics include reaction intermediates (Carbocation,
Carboanion, Free radical and Carbene), Aromaticity, catalysts in organic chemistry, Acidity

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and basicity of organic compounds, polarity etc. These topics often contain questions in the
GPAT exam hence must be studied deeply.
(D) SAR studies of important drug classes
Structural activity relationship is an integral part of the medicinal chemistry. Most of the time
examiner do ask question from this section to check the knowledge of the student. Important
classes of drugs whose SAR studies are of due importance for the GPAT include
Antipsychotics, Diuretics, Benzodiazepines, Acetyl Choline etc.
(E) Spectroscopy
The last but one of the most favourite topics of the examiner is the GPAT. If you are preparing
for GPAT then you can’t neglect the importance of this section. Every year there are definite
questions either on number of signals of NMR, solvents used in different techniques, basic
principles of spectroscopy etc.

OTHER MISCELLANEOUS TOPICS FOR THE GPAT

Beside from these core subjects, there are certain other topics which should also be studied
while preparing for the GPAT. These topics include
a) All schedules of the drugs (Drug and cosmetic act)
b) Vaccine
c) Constitution of AICTE and PCI.
d) Biogenetic precursors of different classes of drugs.
e) Uses of microorganisms
f) Chemotherapy
So, these were the topics which in my analysis are the hottest topics for the GPAT preparation.

PHARMACEUTICS:
LACHMAN – chapter 1 to 7 are important. Chapter 8, 11 – 22 are to be done from this Tables
on page number are important – 27, 37, 44, 98, 151, 165, 174, 321, 357 (only ingredients), 416
(only ingredients), 419, 434, 453, 463, 467, 508, 514, 515, 518, 521, 522, 551, 570 (names
only), 621,631, 634, 642, 646 (tricky question like most permeable can be asked), 648.
MARTIN- if you read Subramanyam whole, then do chapter 1, and last 2 chapters
(biomaterials and delivery systems from it.)
BRAHMANKAR – whole book, read units of various parameters. CDDS. Remember various
release models.
Cosmetics- remember only general things from B. M. Mitthal.

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R. M Mehta – Posology, calculations are important.

COOPER-GUN – read method for sterilization of various injections given at the end of book.
Containers, surgical instruments and sterilization at least see if u get time.
EXTRA – stability testing, ICH guidelines, drug approval process like NDA, ANDA,
ORANGE BOOK.

Intellectual property rights (NIPER only).

What is being studied in NIPER is also asked. (That leave to us)
GMP guidelines.

PHARMACOLOGY:
 Rang and dale remains the standard book for GPAT/NIPER. (Do all important tables from it.)
 K.D TRIPATHI – see haematology, cancer, antibiotics, disinfectants and vaccines from it.
 See adverse drug reactions from ROGER-WALKER book.
 Clinical trials.
 Pharmacological classification from KDT only.

MEDICINAL CHEMISTRY:
 Wilson – read only following things:
 Structures of important drugs(s) and their starting material.

Important SAR related point:

 E.g. position responsible for acid instability of erythromycin. No of isomers for
particular drug.
 Active isomer. Group responsible for activity of drug.
 Which class drug belongs?
 (Chemical class, not pharmacological. Pharmacological class from K.D TRIPATHI
only)

Steroid chapter is very important.

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IUPAC you can see of above drugs from Harkishan Singh book. Just see the structure u will
notice how IUPAC is given for some of above drugs IUPAC Might be complex and lengthy or
not found just leave it.
 Bioisosterism.
 QSAR – From FOYE/SN PANDYA.
 COMPFA like softwares.(NIPER) – LEAVE TO US
 IUPAC from Harkishan Singh book only.

PHARMACOGNOSY:

 Kokate remains the standard book.

 Whole book.
 BS, CC, synonym, use, adulterant, chemical test, substitute, structure (of imp drugs)
 If there are less adulterants or less info about adulterants in Kokate see Trease and
Evans for further.
 Earlier chapters general introduction are important from Kokate.
 WHO guidelines – Kokate is good but with limited information. See other book.
 Biochemical pathways – remember starting points.
 Amino acids from which alkaloids are derived are to be remembered
 E.g tropane alkaloids from ornithine.
 Microscopy of following drugs:
 Read Khandelwall book other than above microscopies full.

ORGANIC CHEMISTRY

 Read only name reactions: Hoffman rearrangement etc.

 Mehta and Mehta or Morrison/Boyd
 Stereochemistry from (M/M or M/M).
 Various catalyst from M/M E.g lindlar catalyst, Wilkinson catalyst
 General concepts from – M/M
 Glossary of M/M

INORGANIC CHEMISTRY:

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 Bahl and Tuli only –thermodynamic and nuclear pharmacy chapters are very important.
Other chapters are also important.
 Chatwal – remember only common names of compounds and their use and water for
injection limits.

MICROBIOLOGY

 Only Kokare (whole book) is enough.

 Vaccines read from it and also IP
 Something from Tortora (For NIPER– we will say later).
 Diagnostic tests.

BIOCHEMISTRY

 Satyanarayan is enough:
 Do chapters 1 to 7 and metabolism chapters.
 Do all important tables.
 Biochemical teats (from R.K. GOYAL - available in GUJARAT only others students
should see SATYANARAYAN AND KALE BOOK)

PHARMA ANALYSIS:

 MASS – SILVERSTEIN, KASTURE, RAVISHANKAR.

 N – RAVISHANKAR, KASTURE, KEMP. (NIPER – PAVIA)
 UV, IR – RAVISHANKAR, KASTURE, CHATWAL/YR SHARMA.
 AAS/FLAME PHOTOMETRY/FLUORIMETRY – RAVISHANKAR, KASTURE.
 GRAVIMETRY/REDOX/ACID- BASE/POALRIMETRY/POLAROGRAPHY/
 CONDUCTOMETRY/AMPEROMETRY /ETC– RAVISHANKAR KASTURE.
 CALCULATIONS - UNDERWOOD.
 DSC/DTA/TGA – MARTIN, REMINGTON,
 KARL-FISCHER/KJELDAHL/CAURIUS/DUMAS etc determination methods - bahl
and bahl or any other book.
 Assays- KASTURE OR RAVISHANKAR.

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 See analysis part from /REMINGTON also.

 Circular dichronism.
 Chromatography – RAVISHANKAR/KASTURE.

JURISPUDENCE

 GK JANI/ KUCHEKAR.
 Read important years.
 D and C act
 Schedules
 Form numbers
 Members
 Place of various institutes.

NIPER ONLY READ FOR NIPER BEFORE GPAT.

 Biostatistics general concepts
 Management/accountancy/partnership: use Gujarat board 11 or 12 standard books like
– accountancy, secretial practice etc. or what is studied in NIPER.
 Noble prize winners recent.
 Pharma news recent
 General knowledge.
 Apptitude (Maths)
 Recent approved USFDA DRUGS (do only approved in May/June/July –upto NIPER
exam date)
 Banks full forms and when they established.
 Pharmaceutical full forms.
 Name and location of important institutes.
 Any other useful information which we say at last time.

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 GPAT 2020
BOOKLET

PART III
STUDY M ATERIAL
M R. AM AR M . RAVAL (M .PHARM )
TEST PAPER-10 PHARM ACEUTICAL CHEM ISTRY GPAT TEST SERIES BY PHARM AROCKS

PHARMAROCKS
THE WAY OF SUCCESS

GPAT STUDY MATERIAL

MR. AMAR M. RAVAL

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PHARM AROCKS GPAT SUCCESS SERIES-2016: THE W AY OF SUCCESS IM P STUDY M ATERIAL

DRUGS AND THEIR ACTIVE METABOLITES

SR.NO. DRUG ACTIVE METABOLITE

1 Allopurinol Oxipurinol (Alloxanthine)
2 Amytryptylline Nortryptalline
3 Amphetamine P-Methoxy Amphetamine
4 Carmapazepine Carmapazemine-10,11-Eporide
5 Carbimazole Thiamazole
6 Cephaloglycine Desacetyl Cephaloglycine
7 Chloral Hydrate Trichloroethanol
8 Chlordiazepoxide 7-hydroxy Chloropromazine
9 Chlorpromazine 7-hydroxy Chloropromazine
10 Chlorguanidine Cyclogunal
11 Clofibrate Free acid metabolite
12 Imipramine N-oxide metabolite
13 Codeine Morphine,Norcodeine
14 Diazepam Oxazepam.N-Me-Oxazepam
15 Fenfluramine Nor Fenfluramine
16 Guanethadine N-Oxide
17 Lignocaine N-Desmethyl metabolite
18 Morphine Nor morphine
19 Naloxane 6-฀-hydroxy Naloxane
20 Phenacetin Paracetamol
21 Prednisone Prednisolone
22 Premidone Phenobarbitone
23 Spironolactone Canrenone
24 Procainamide N-Acetyl metabolite
25 Propanolol N-deisopropyl met
26 Quinidine 3-Hydroxy quinone
27 Rifampicine Desacetylated metabolite
28 Thioridazine Mesoridazine

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29 Trimethedione Dimethedione
30 Warfarin Warfarin alcohol
31 Vit D 1,2 Dihydroxy metabolite
32 Reserpine Methyl reserpate

PRODUCTS AND ANIMALS USED FOR BIOASSAYS

SR DRUG PRODUCT ANIMAL

1 Digitalis Pigeon

2 Glycogen Cat

3 Insulin inj, Rabbit

4 Oxytocin Chicken

5 Parathyroid Dog

6 Vasopressin Rat

7 Posterior pituitary Chicken

8 Tubocurarine chloride Rabbit

9 Chorionic gonadotropin Male rat

10 Cod liver oil Rachitic rat

11 Heparin sodium Sheep

12 Iron dextran injection Microbial cultures

13 Antiseptic and disinfectant Frog

14 Fungicides and Herbicides Mouse

15 Diphtheria toxoid Rat

16 Atropine Rabbit

17 Insulin inj. Guinea pig

18 Elastomeric closures Plastic containers Guinea pig

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RECOMENDE NEEDLE SIZE FOR VARIOUS INJECTIONS

INJECTIONS GUAGE LENGTH IN INCHES

INTRADERMAL 26G ¼ or 3/8

S.C 26G ½-¾

25G ½-¾

22G 1½

I.M 24G ¾-1

23G 1

22G 1

20G 1½

I.V 22G 1-1/4-1 ½

20G 1½

DRUGS AND THEIR VARIETIES

DRUG VARIETY
1 SENNA
Indian senna Cassia angustifolia
Alexandrian senna Cassia acutifolia
Dog senna Cassia obovata
Palthe senna Cassia auriculata
2 ALOE
Cape Aloe Aloe ferox
Curcao Aloe Aloe barbadensis
Socotriene/ Zangibar aloe Aloe perryii
3 RHUBARB
Indian Rhubarb Rheum emodi
Chienese Rhubarb Rheum Webbianum

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DRUG AND THEIR SYNONYMS

SR.NO. DRUG SYNONYMS

1 Cinchona Panama bark

2 Lanolin Wool fat
3 Crowfig seeds Nuxvomica
4 Deadly night shade Atropa beladona
5 Digitalis purpuria Foxglove
6 American podophyllum May apple
7 Indian tragacanth Gum karaya
8 Devil’s dung Asafoetida
9 Indian squill Urgenia
10 Indian tobacco Lobelia
11 Flax seeds Linseed
12 Periwinkle Vinca visea
13 Ashwagandha Withania somnifera
14 Alexendrian senna Cassia acutifolia
15 Tinevally senna Cassia angustifolia
16 Dog senna Cassia obovata
17 Pathe senna Cassia auriculata
18 Acasia Gum arabica
19 Sterculia Karaya
20 Agar Japnese is linglass
21 Plantago Psyllium
22 Starch Amylum
23 Rhubarb Rheam.emodi.(IND.Rhubarb)
24 Cascara Purshiana,sacred barc
25 Discoria Wild Yam
26 Glycerrhiza Liquarice
27 Quillalia Panama bark
28 Quassia Bitter wool

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29 Pale calicher Gambier catechu

30 Blach caticher Cutch
31 Castor oil Ricinus oil
32 Arachis oil Reauut oil
33 Linseed iol Flax seed oil
34 Olive oil Saled oil
35 Hydro carpno oil Chanlmogra oil
36 Theobrona oil Cocoa butter
37 Cinnamon Chinese cassia
38 Saffron Crocus
39 Colchicum Autumn Crocus, Meadow saffron seeds
40 Nutmeg Mygistica
41 Chenopodium American wore
42 Lipstick tree Annato tree, Bixin
43. Clove Caryo phylum

NAME OF THE DRUG AND SIDE EFFECTS

SR NO NAME OF THE DRUG SIDE EFFECTS

1 ACE Inhibitors Dry Cough

2 Amphotericin-B Nephrotoxicity
3 Ampicillin Hypersensitivity
4 Androgen Virilization
5 Antipsychotics Sedation,
Orthostatic hypotension,
Tardive dyskinesia
6 Anti- TB Hepatotoxicity
7 Aspirin (cox-I Inhibitors) Hepatotoxicity
8 Atropine Dryness of mouth,
Blurred vision,
Constipation

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PHARM AROCKS GPAT SUCCESS SERIES-2016: THE W AY OF SUCCESS IM P STUDY M ATERIAL

9 Celecoxib, Hepatotoxicity
Valdecoxib (cox-II Inhibitors)
10 Chlorambucil Alopecia
11 Chloramphenicol Grey baby syndrome,
Bone marrow depression
12 Chloroquine Phototoxicity
13 Ciprofloxacin Phototoxicity
14 Clofazimine Pigmentation of skin,
Discoloration of Urine
15 Clozapine Agranulocytosis
16 Erythromyicin Cholestatic Juandice
17 Ethambutol Optic Neuritis,
Retrobulbular Neuritis
18 Hydrochlorthiazide Hypokalamia
19 Isoniazid Peripheral Neurtis
20 Metronidazole Disulfiram like reaction
21 Minoxidil Hirsutism
22 Morphine Constipation
23 Nimesulide Hepatotoxicity
24 Nitrogen Mustard Bone marrow depression
25 Nitroglycerin Palpitation
26 Penicillin-G Jarisch Heximer Reaction
27 Phenformin Lactic acidosis,
GI disturbance,
Metalic taste
28 Phenytoin Hirsutism
29 Quinidine Cinchonism
30 Quinine Sulphate Black Water Fever
31 Repaglinide Althralgia
32 Rosaglitazone Anemia,Weight gain
33 Sitagliptin Coldness

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34 Spironolactone Hyperkalamia
35 Cimetidine Gynacomastia
37 Sulfonyl Ureas derivatives Bone marrow depression
38 Terfenadine Type-I arrhythmia
39 Tetracyclines Discoloration of teeth
40 Thalidomide Phocomelia

CAPSULE NO & THEIR APPROXIMATE CAPACITY IN mg & ml

CAPSULE SIZE Mg Ml
000 (Largest) 950 1.37
00 650 0.95
0 450 0.68
1 300 0.50
2 250 0.37
3 200 0.30
4 150 0.21
5 (Smallest) 100 0.13

PROPORTIONS REQUIRED FOR A PRIMARY EMULSION

TYPE OF OIL OIL: WATER: GUM RATIO

FIXED OILS 4:2:1
VOLATILE OILS 2:2:1
MINERAL OILS 3:2:1
OLEORESINS 1:2:1

CODE: LPSO (APPLY THIS FOR TWEENS & SPANS)

For eg. SPANS 20 MEAN SORBITAN MONO LAURATE
TWEEN 80 MEAN POLYOXYETHYLENE SORBITAN MONOOLEATE
 L : LAURATE - 20

 P : PALMITATE - 40

 S : STEARATE - 60

 O : OLEATE - 80

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SOLUBILITY

Descriptive Term Approx. Vol of Solvent in ml/gm of Solute

Very soluble less than 1

Freely soluble 1 to 10

Soluble 10 to 30

Sparingly soluble 30 to 100

Slightly soluble 100 to 1000

Very slightly soluble 1000 to 10,000

Practically insoluble more than 10,000

STORAGE TEMPERATURE

COLD TEMPERATURE 2 to 8 degree centigrade

COOL TEMPERATURE 8 to 25

ROOM TEMPERATURE Prevailing in the working area

WARM TEMPERATURE Between 30 to 40

EXCESSIVE HEAT > 40 degree

SUCROSE BASED DILUANTS

DIPAC 97 % sucrose + 3% moddified dextrose
NUTAB 95 % sucrose + 4 % invert sugar
SUGAR TAB 90 - 93 % sucrose + 7 - 10 % invert sugar

Carr’s index
The bulk density was the quotient of weight to the volume of the sample. Tapped density was
determined as the quotient of weight of the sample to the volume after tapping a measuring
cylinder for 500 times from a height of 2 inch. The Carr’s index (percentage compressibility)
was calculated as one hundred times the ratio of the difference between tapped density and
bulk density to the tapped density

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% Carr’s Index = (Tapped density – Bulk density) / Tapped density * 100

% Carr’s Index = (TD – BD) / TD * 100

Hausner’s Ratio
Hausner’s ratio is the ratio of tapped density to the bulk density.

Hausner’s Ratio = Tapped density / Bulk density H.R = TD / BD

% CI FLOW CHARACTER HAUSNER RATIO

< or = 10 Excellent 1 - 1.11
11 – 15 Good 1.12 - 1.18
16 – 20 Fair 1.19 - 1.25
21 – 25 passable 1.26 - 1.34
26 – 31 poor 1.35 - 1.45
32 – 37 very poor 1.46 - 1.59
>38 very very poor > 1.6

Angle of repose
The angle of repose is a relatively simple technique for estimating the flow properties of a
powder. It can easily be determined by allowing a powder to flow through a funnel and fall
freely onto a surface. The height and diameter of the resulting cone are measured and the
angle of repose calculated from this equation:
Tan Ø = h/r
Where, ‘h’ is the height of the powder cone and ‘r’ is the radius of the powder cone.
ANGLE OF REPOSE FLOW CHARACTER
25 – 30 Excellent
31 – 35 Good
36 – 40 Fair
41 – 45 Passable
46 – 55 Poor
56 – 65 Very Poor
>66 Very Very Poor

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TYPES OF GLASS USED IN PHARMACEUTICAL INDUSTRIES

Parenteral Use
 Type I Glass:
 Highly Resistant Borosillicate.
 Used for Buffered and Unbuffered aqueous solution.

 Type II Glass:
 Highly Resistant Sodalime glass.
 Buffered aqueous solution below pH 7.0

 Type III Glass:

 Moderately Resistant Sodalime glass.
 Used for dry powder and oily solution.

 Non-Parenteral Use
 Type IV Glass:
 General Purpose Sodalime glass.
 Not for parenteral, for tablet, liquid oral and externals.

ANTIDOTES FOR SOME DRUGS

SR NO DRUG NAME ANTIDOTE

1 Acetaminophen NAC (N-acetyl-L-cysteine) dosage

Alcohols (ethylene glycol, IV ethanol, fomepizol (potent inhibitor of ADH)

2 methanol)

3 Heparin Protamine

4 Warfarin vitamin k

5 Antidepressants

TCA’s benzodiazepines, phenytoin, physiostigmine

SSRI’s Cycloheptadine

6 6.Benzodiazepines Flumazenil

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7 7.Beta antagonists glucagon and epinephrine

8 Calcium antagonists calcium, glucagon, insuline & dextrose combination

Cocaine BZD’s for seizuries; labetalol for hypertension;

9 Neuroleptics for psychosis

10 Cyanide amyl nitrite; sodium nitrite; sodium thio sulphate

11 Digoxin Digibind

12 12.Electrolytes

a.Magnesium 10%CaCl2 temp to antagonize cardiac effects of Mg

b.Potassium- 10%CaCl2 10%; NaHCO3(causes intracellular shift

of pot);

13 Iron deferoxamine (chelate iron)

14 Isoniazid pyridoxine (reverses INH induced seizures)

15 Lead Ca Disodium EDTA ; BAL (dimercaprol)

16 Lithium no effective treatment

17 Opiates naloxone; nalmefene

18 Organophosphates atropine; pralidoxamine

19 Salicylates activated charcoal

20 Theophylline charcoal; beta antagonists

glucose & Insulin sodium polystyrene sulfonate

21 (Intracellular shift of pot.) (cationic exchange resin)

SYNONYMS AND THEIR COMMON NAMES

SR NO SYNONYM COMMON NAME

1 Rochelle salt Sodium Potassium Tartarate
2 Dakin’s solution Sodium Hypochloride
3 Glaubers salt Sodium Sulphate
4 Epsom salt Magnesium Sulphate

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5 China clay Heavy Kaolin

6 Gypsum Calcium Sulphate
7 Calomel Mercurous Chloride
8 Soap clay Bentonite
9 French chalk Talc
10 Alum Potassium Aluminium Sulphate
11 Hypo Sodium Thiosulphate
12 Precipitated chalk Calcium Carbonate
13 Slaked lime Calcium Hydroxide
14 Bleaching powder Chlorinated Lime
15 Burrows solution Aluminium Acetate Solution
16 Laughing gas Nitrous Oxide
17 Tear gas (CS gas) Chlorobenzylidine Malononitrile
18 Iodine tincture Weak Iodine Solution
19 knock out drops Chloral Hydrate
20 Washing soda Sodium carbonate
21 Baking soda Sodium bicarbonate
22 Costic soda Sodium hydroxide
23. Lugols solution Aqueous Iodine Solution

VACCINES

LIVE ATTENUATED: INACTIVATED RECOMBINANT:

MEASLES RABIES HEPATITIS B

MUMPS INFLUENZA

POLIO TETANUS TOXOID:

RUBELLA HEPATITS A DIPTHERIA
TYPHOID TETANUS
VARICELLA

TUBERCULOSIS
YELLOWFEVER

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TEST ORGANISM FOR MICROBIOLOGICAL ASSAY OF ANTIBIOTIC

SR NO ANTIBIOTIC TEST ORGANISM

1 Amikacin Staphlococcus aureus

2 Amphotericin B Saccharomyces cerevisiae

3 Bacitracin Micrococcus luteus

4 Bleomycin Mycobacterium smegmatis

5 Carbenicillin Pseudomonas aeruginosa

6 Doxycycline Staphlococcus aureus

7 Erythromycin Micrococcus luteus

8 Framycetin Bacillus pumilis , staphylococcus aureus

9 Gentamycin Staphylococcus epidermidis

10 Kanamycin Bacillus pumilis, staphylococcus aureus

11 kanamycin B Bacilus subtilis

12 Neomycin Staphlococcus epidermidis

13 Novobiocin Staphlococcus epidermidis

14 Nystatin Saccharomyces cerevisiae

15 Oxyteracycline Bacillus cereus, staphylococcus aureus

16 Polymyxin B Bordetella bronchiseptica

17 Rifamycin Bacillus subtilis

18 Streptomycin Bacillus subtilis , klebsiella pneumoniae

19 Tetracycline Bacillus cereus, staphylococcus aureus

DISEASE ASSOCIATED WITH ALTERED NEUROTRANSMITTERS LEVELS IN BRAIN

SR NO DISEASE NEUROTRANSMITTERS LEVELS

1 Parkinsonism Decreased DOPAMINE in striatum
2 Schizophrenia Increased DOPAMINE levels

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3 Depression Decreased NOREPINEPHRINE & 5-HT

4 Mania Decreased NOREPINEPHRINE & 5-HT

5 Hallucination Increased 5-HT
Decreased ACETYLCHOLINE & Destruction
6 Alzheimer’s
of Cholinergic Neurons
7 Athetosis Decreased GABA in Putamen
8 Chorea Decreased GABA in Caudate Nucleus

9 Amyotropic lateral sclerosis Decreased ACETYLCHOLINE

ENZYMES AND THEIR METAL COFACTORS

FE2+ CYTOCHROMEOXIDASE, CATALASE, PEROXIDASE

CU2+ CYTOCHROME OXIDASE

DNA POLYMERASE, CARBONIC ANHYDRASE,

ZN2 +
ALCOHOL DEHYDROGENASE

MG2 + HEXOKINASE, GLUCOSE 6 PHOSPHATE

MN2+ ARGINASE

K+ PYRUVATE KINASE

NI2+ UREASE

MO NITRATE REDUCTASE

SE GLUTATHIONE PEROXIDASE

MICROSOMAL ENZYMES INDUCERS AND INHIBITORS

MICROSOMAL ENZYME INDUCERS

ALCOHOL
CHLORALHYDRATE
CORTISONE

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NICOTINE
PREDNISOSLONE
PHENYTOIN
CHLORDIAZEPOXIDE
IMIPRAMINE
PHENOBARBITAL
TESTOSTERONE

MICROSOMAL ENZYME INHIBITORS

ALLOPURINOL
ORAL ANTIDIABETICS
DISULFIRAM
METRONIDAZOLE
ORAL ANTICOAGULANTS
ANABOLIC AGENTS
CHLORAMPHENICOL
ISONIAZID
MONOAMINE OXIDASE INHIBITORS
CEMETIDINE

DISEASE DEFECTIVE ENZYME

ALBINISM - TYROSINE-3-MONO OXYGENASE
ALKAPTONURIA - HOMOGENTISATE1,2-DIOXYGENASE
GALACTOSE-1-PHOSPHATE IRIDYLYL
GALACTOSEMIA -
TRANSFERASE
HOMOCYSTINURIA - CYSTATHIONE B- SYNTHASE
PHENYLKETONURIA - PHENYLALANINE-4-MONO OXYGENASE
TAYSACHS DISEASE - HEXOSAMINIDASE A
HYPERVALINEMIA - VALINE TRANSAMINASE
ARGINOSUCCINIC - ARGINOSUCCINATE LYASE ACIDEMIA
KRABBES DISEASE - BETA GALACTOSIDASE

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FABRYS DISEASE - ALPHA GALACTOSIDASE

NIEMANN PICK DISEASE - SPHINGOMYELINASE
FARBERS DISEASE - CERAMIDASE
GAUCHERS DISEASE - BETA GLUOSIDASE

DIAGNOSTIC TESTS

NAME OF DISEASE DIAGNOSTIC TESTS

1. VDRL TEST,
2. KAHN TEST,
3. WASSERMAN TEST
SYPHILIS
4. TREPONEMA IMMOBILIZATION TEST,
5. FLUROESCENT ANTIBODY-ABSORBED
SERUM TEST.

1. SCHICK TEST,
DIPTHERIA
2. ELEX TEST

T.B TUBERCULIN, MANTOUX TEST

LEPROSY LEPROMIN TSEST

TYPHOID OR ENETRIC FEVER WIDAL TEST

RHUMETOID ARTHRITIS ROSE WATER TEST

SMALL POX OUCHTERLONY

1. COLD HEMAGLUTINATION TEST,

PNEUMONIA 2. STREPTOCOCCUS MG
HEMAGLUTINATION TEST

BRUCELLOSIS- COOMBS TEST(OPSONIZATION TEST)

LYMPHOGRANULOMA
FREI TEST
VENERUM

TYPHUS FEVER- WEIL FELIX TEST

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HEMOPHILLIUS- DUCREY TEST

SCARLET FEVER- DICK TEST

TO DETECT HUMAN CHORNIC

GONADOTROPHIN IN SERUM RADIO IMMUNO ASSAY(RIA)
OF WOMAN

BIOASSAYS OF DRUGS AND ITS EFFECT ON THE ANIMAL

ADRENALINE BP raising effects in spinal cats

NORADRENALINE BP raising effects in spinal cats

HISTAMINE Contraction of isolated guinea pig ileum

INSULIN Hypoglycemic convulsions in mice

ACETYLCHOLINE Contraction of isolated frog rectus muscle

D TC Rabbit head drop due to paralysis of neck muscles

DIGITALIS Death due to cardiac arrest in guinea pig

OXYTOCIN Contraction of guinea pig uterine muscles

ANDROGENS Growth copons comb

ADRENO CORTICO
Adrenal ascorbic acid estimation in hypophysectomised rats
TROPIC HORMONE

MICRO ORGANISMS USED AS BIOASSAYS FOR VITAMINS

ASSAY MICRO ORGANISM VITAMIN

BIOTIN,
FOLICACID,
Lactobacillus casei
PYRIDOXAL,
RIBOFLAVINE

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CALCIUM PANTOTHENATE,
L. Arabinosus
NICOTINIC ACID

L.leichmanii CYANOCOBALAMIN

L.viridans THIAMINE

Saccharomyces urarum INOSITOL

Acetobacter suboxydans PANTHOTHENOL

Neurospora crassa (or) s.carlsberginsis PRIDOXINE

BIOLOGICAL INDICATORS

Moist heat sterilisation (121 degre Centi ) Bacillus stearo thermophilus

Dry heat sterilisation (160 degre centi) Bacillus subtilis var niger

Hydrogen peroxide and peracetic acid Bacillus stearo thermophilus

Ethylene oxide , formaldehyde Bacillus subtilis var niger

Ionising radiation Bacillus pumilis

TESTS AND THEIR USES

SR NO TEST IDENIFY
1 Watson Schwartz Test Urobilinogen
2 Schumms Test Heme
3 Carrprice Test Vit A
4 Gmelins Test Bile Pigments
5 Gothlin Test Scurvy
6 Gofmann Test Serum Cholesterol
7 Murexide Test Uric Acid
8 Reinsch Test Heavy Metals

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9 Gordons Test Spinal Fluid

10 Biuret Test Peptides

11 Legals Test For Estimation Of Acetone
12 Ames Test Carcinogenicity

SHORT CUTS FOR GPAT AND NIPER (EASY TO REMEMBER)

Busulfan feature: ABCDEF

 Alkylating agent

 Bone marrow suppression

 CML Indication

 Dark skin(hyperpigmentation)

 Endocrine insufficiency(adrenal)

 Fibrosis

Drugs causing Torsades de Pointes: APACHE

 Amiodarone

 Procainamide

 Arsenium

 Cisapride

 Haloperidol

 Erythromycin

Morphine side effects: MORPHINE

 Myosis

 Out of It (sedation)

 Respiratory depression

 Pneumonia(aspiration)

 Hypotension

 Infrequency (constipation,urinary retention)

 Nausea

 Emesis

Aspirin side effects: ASPIRIN

 Asthma

 Salicylism

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 Peptic ulcer disease/phosphorylation-oxidat

 ion uncoupling/platelet disaggregation

 Intestinal blood loss

 Reye's Syndrome

 Idiosyncracy

 Noise(tinnitus)

SSRIs side effects: SSRI

 Seratonin syndrome

 Stimulate CNS

 Reproductive disfunction in male

 Insomnia

Inhalation anesthetics: SHINE

 Sevoflane

 Halothane

 Isoflurane

 Nitrous oxide

 Enflurane

Teratogenic drugs:"Win Teratogenic

 Warfarin

 Thalidomide

Epileptic drugs:
 Phenytoin,

 Valproate,

 Amazepine

 Retinoid

 ACE inhibitor

Third element: Lithium

Gynaecomastia causing drugs: DISCOS
 Digoxin

 Isoniazid

 Spironolactone

 Cimetidine

 Oestrogens

 Stilboestrol

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Methyldopa Side effects: METHYLDOPA

 Mental retardation

 Electrolyte imbalance

 Tolerance

 Headache/ Hepatotoxicity

 Psychological upset

 Lactation in female

 Dry mouth

 Oedema

 Parkinsonism

Antirheumatic agents: CHAMP

 Cyclophosphamide

 Hydroxycloroquine and choloroquinine

 Auranofin and other gold compounds

 Methotrexate

 Penicillamine

Phenytoin: adverse effects PHENYTOIN

 P-450 interactions

 Hirsutism

 Enlarged gums

 Nystagmus

 Yellow-browning of skin

 Teratogenicity

 Osteomalacia

 Interference with B12 metabolism (hence anemia)

 Neuropathies: vertigo, ataxia, and headache

Sodium Valproate side effccts VALPROATE

 Vomiting

 Alopecia

 Liver toxicity

 Pancreatitis/ Pancytopenia

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 Retention of fats (weight gain)

 Oedema (peripheral oedema)

 Appetite increase

 Tremor

 Enzyme inducer (liver)

Amiodarone: action, side effects: 6 P's:

 Prolongs action potential duration

 Photosensitivity

 Pigmentation of skin

 Peripheral neuropathy

 Pulmonary alveolitis and fibrosis

 Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism

Antiparkinson Drugs: SALAD

 Selegiline

 Anticholinenergics (trihexyphenidyl, benzhexol, ophenadrine)

 L-Dopa + peripheral decarboxylase inhibitor (carbidopa, benserazide)

 Amantadine

 Dopamine postsynaptic receptor agonists (bromocriptine, lisuride, pergolide)

Therapeutic Index Formula TILE

TI = LD / ED

Anti epeleptic drugs Dr.BHAISAB's New PC.

 Deoxy barbiturates

 Barbiturates

 Hydantoin

 Aliphatic carb acids

 Iminostilbenes

 Succinimides

 BZD's

 Newer drugs

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 Phenyltriazines

 Cyclic GABA analogues

Adverse effects of Tetracyclines-KAPIL DEV

 Kidney toxicity

 Antianabolic effect

 Phototoxicity

 Liver toxicity

 Diabetes insipidus

CAPTOPRIL Side effects CAPTOPRIL

 Cough Angioedema

 Agranulocystosis

 Proteinuria/ Potassium excess

 Taste changes

 Orthostatic hypotension

 Pregnancy contraindication/ Pancreatitis/ Pressure drop (first dose hypertension)

 Renal failure (and renal artery stenosis contraindication)/ Rash

 Indomethacin inhibition

 Leukopenia/Liver toxicity

Lithium: side effects LITH

 Leukocytosis

 Insipidus [diabetes insipidus, tied to polyuria]

 Tremor/ Teratogenesis

 Hypothyroidism

Myocardial Infarction (MI): signs and symptoms PULSE

 Persistent chest pains

 Upset stomach

 Lightheadedness

 Shortness of breath

 Excessive sweating

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MI: basic management BOOMAR

 Bed rest

 Oxygen

 Opiate

 Monitor

 Anticoagulate

 Reduce clot size

Treatment of Heart Failure: ABCDE

 ACE inhibitors

 Beta-blockers

 Calcium channel blockers

 Diuretics

 Endothelin-converting enzyme inhibitors

Essential Amino acids

My True Love Is Throug Valentine Love Phrases
 Methionine

 Threonine

 Leucine

 Isoleucine

 Tryptophan

 Valine

 Lysine

 Phenyl alanine

BLOOD GROUP AND ITS COLOR OF LABEL MOST IMP

BLOOD GROUP COLOR OF LABEL

O BLUE

A YELLOW

B PINK

AB WHITE

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ABBREVIATIONS IMP FOR GPAT AS WEL AS IN NIPER

Description of some Important Abbreviations:-
ABBREVIATIONS FULL FORM
AAAS American Association of Advancement of Science
AALAS American Association for Laboratory Animal Science
AIOPI Association of Information Officers of the Pharmaceutical Industry
ALF American Liberation Front
ANDA Abbreviated New Drug Application
BEA Breeding for Experimental Animals
BINAS Biosafety Information Network and Advisory Service
BMA British Medical Association
BMJ British Medical Journal
BPC Bulk Pharmaceutical Chemicals
BPI British Pharmaceutical Index
BrAPP British Association of Pharmaceutical Physicians
BUAV British Union for the Abolition of Vivisection
CADD Computer Aided Drug Design
CDC Centre for Disease Control
CIOMS Council for International Organisations of Medical Sciences
Committee for Purpose of Control & Supervision of Experimental
CPCSEA
Animals
CPI Consumer Price Index
CRA Clinical Research Associate
CRC Clinical Research Council
CRF Case Report Form
CRN Clinical Research Network
CRO Contract Research Organisation
CSM Committee on Safety of Medicines
CTA Clinical Trial Authorisation (formerly the CTX, CTC, DDX)
CTC Clinical Trial Certificate (Now CTA)
CTC Clinical Trials Centre

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CTD Common Technical Document

CTD Common Technical Document
CTX Clinical Trial Exemption (Now CTA)
DRA Drug Regulatory Affairs
DUMP Disposal of Unwanted Medicines and Poisons
EFPIA European Federation of Pharmaceutical Industries & Associations
EMEA European Medicine Agency
FDA Food & Drug Administration
FIP International Pharmaceutical Federations
GCP Good Clinical Practices
GLP Good Laboratory Practices
GMP Good Manufacturing Practices
Generic term for good practice requirements in the Pharmaceutical
Gxp
industry
HIS Indian Health Services
HPLC High Performance Liquid Chromatography
HRSA Health Resources & Service Administration
IACUC Institutional Animal Care and Use Committee
IAES Institutional Animal Ethics Committee
ICDRA International Conference for Drug Regulatory Authorities
International Conference on Harmonization of technical requirement
ICH
for registration of pharmaceuticals
IIG Inactive Ingredient Guide
Investigational Medicinal Products IMP - Investigational Medicinal
IMP
Products
IMPD Investigational Medicinal Product Dossier
INDA Investigational New Drug Application
INN International non-proprietary names (for pharmaceutical substances)
International Drug Information System - the previous WHO adverse
INTDIS
reactions database
IPC Indian Pharmaceutical Congress

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IPGA Indian Pharmacy Graduate Association

ISO International Organization for Standardization
ISoP International Society of Pharmacovigilance
ISPE International Society for Pharmacoepidemiology
MedDRA Medical Dictionary for Drug Regulatory Affairs
National Agency for Food and Drug Administration and Control,
NAFDAC
Nigeria
NCPA National Community of Pharmacist Association
NCPO National Conference of Pharmaceutical Organisations
NDA New Drug Application
NDMS National Disaster Medical System
NME New Molecule Entity
NSAID Non-Steroidal Anti-Inflammatory Drug
OTC Over-The-Counter
PDS Pharmacoepidemiology and Drug Safety (journal)
PEM Prescription Event Monitoring
PHRMA Pharmaceutical Research and Manufacturers Association
PIL Package Insert Leaflet
PMDA Pharmaceuticals and Medical Devices Agency, Japan
PMS Post-Marketing Surveillance
POM Prescription Only Medicine
PSM Procurement and Supply Management
PSUR Periodic Safety Update Report
QA Quality Assurance
QSM-WHO Quality Assurance and Safety of Medicines (WHO)
R&D Research and Development
RAPS Regulatory Affairs Professionals Society
RCT Randomised Clinical Trials
RDE Remote Data Entry
RDS Research Defence Society
REC Research Ethics Committee

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RGN Registered General Nurse

RPSGB Royal Pharmaceutical Society of Great Britain
RSM Royal Society of Medicine
Rx Prescription (YOU TAKE)
SARS Severe Acute Respiratory Syndrome
SCDM Society for Clinical Data Management
SIDS Sudden Infant Death Syndrome
SIGAR Special Interest Group on Adverse Reactions
TGA Therapeutic Goods Administration, Australia
TMF Trial Master File
TUFAM General Directorate of Pharmaceuticals and Pharmacy, Turkey
UDV Unit Dose Vial
UKECA United Kingdom Ethics Committee Authority
USP United States Pharmacopoeia
WIPO World Intellectual Patent Office

SCHEDULES TO THE RULES

SCHEDULES THE RULES

Perform for application for the licences, issues and renewal of licences, for
A
sending memoranda under the Act.

Rates of fee for test or analysis by the Central Drugs Laboratory or the
B
Government analysist.

List of biological and other special products whose import, sale, distribution
C
and manufacturing are a governed by special provision.

List of other special products whose import, sale, distribution and

C1
manufacturing are governed by special provision.

D List of drugs exempted from the provisions of import of drugs.

List of poisionous substances under the Ayurvedic (including Sidha) and

E1
Unani systems of medicine.

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Provisions applicable to the production, testing, storage, packing and

F & F1
labeling of biological and other Special products.

F2 Standards for surgical dressings.

F3 Standards for sterilized umbilical tapes.

FF Standards of ophthalmic preparations.

List of substances that are required to be used only under medical

G
supervision and which are to be labeled accordingly.

H List of prescription drugs.

J Disease or ailments which a drug may not purport to prevent or cure.

K Drugs exempted from certain provision relating to manufacture of drugs.

M GMP requirement of factory premises, plants and equipment.

Requirement of factory premises etc. for manufacture of homoeopathic

M1
preparation.

M2 Requirement of factory premises etc. for manufacture of cosmetics.

N List of minimum equipment for efficient running of a pharmacy.

O Standard for disinfectant fluid.

P Life period of drug.

Q List of coals tar color permitted to be used in cosmetics.

R Standard for mechanical contraceptive. CONDOMS

S Standard for cosmetics.

Requirement of factory premises and hygienic condition for Ayurvedic

T
(including Sidha) and Unani drugs.

Particulars to be shown in manufacturing, raw material and analytical

U
records of drug.

Particulars to be shown in manufacturing, raw material and analytical

U1
records of cosmetics.

V Standard for patent or proprietary medicines.

W List of drug which is to be marketed under generic names only.

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List of drugs whose import, manufacture and sale, labeling and packaging
X
are governed by special provision.

Requirement and guideline on clinical trials for import and manufacture of

Y
new drug.

BETA BLOCKERS

Comparative information Pharmacological differences

Agents with intrinsic sympathomimetic action (ISA)
 Acebutolol,

 Carteolol,

 Celiprolol

 Mepindolol

 Oxprenolol

 Pindolol

Agents with greater aqueous solubility (hydrophilic beta blockers)

 Atenolol

 Celiprolol

 Nadolol,

 Sotalol

Agents with membrane stabilizing effect

 Acebutolol,

 Betaxolol,

 Pindolol,

 Propranolol

Agents with antioxidant effect

 Carvedilol,

 Nebivolol

INDICATION DIFFERENCES
Agents specifically indicated for cardiac arrhythmia
 Esmolol,

 Sotalol,

 Landiolol

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Agents specifically indicated for congestive heart failure

 Bisoprolol,

 Carvedilol,

 Sustained-release metoprolol,

 Nebivolol

Agents specifically indicated for glaucoma

 Betaxolol,

 Carteolol,

 Levobunolol,

 Metipranolol,

 Timolol

Agents specifically indicated for myocardial infarction

 Atenolol,

 Metoprolol,

 Propranolol

Agents specifically indicated for migraine prophylaxis

 Timolol,

 Propranolol

Propranolol is the only agent indicated for control of tremor, portal hypertension, and
esophageal variceal bleeding, and used in conjunction with α blocker therapy in
phaeochromocytoma.

SOME IMP PH VALUE

Blood: 7.4
Tear 7.2
Skin 7.4
Secretion of Skin: 5.5
Gastric juice: Infants: 5, Adults: 2
Saliva: 6.3-6.7
Urine: 4.4-8

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Stool: approx. 6
Bile Juice: 8-8.6
Semen: 7.2-8
Vagina: 3.8-4.5

MECHANISM OF ACTION

1-DNA Dependent RNA Polymerase- Rifampcin

2- RNA Dependent DNA Polymerase- Zidovudine
3-Proetin Synthesis Blocker- Erythromycin, Chloramphenicol & Tetracycline
4-ACE Inhibitor- Captopril
5-Ca Channel Blocker- Nifedipine, Diltiazem
6-COX Inhibitor- Asprin
7-GABA Facilitator- Benzodiazepines
8-Antimetabolites- Methotrexate
9-Loop Diuretics- Frusemide
10-High Ceiling Diuretics- Spironolactone
11-Alteration of bacterial DNA- Choloroquine
12-Inhibition of Viral replication- Amantidine, Acyclovir
13-H1 blocking agent- Mepyramine, Loratadine
14-H2 Blocking agent- Rantidine, Cimetidine, Famotidine, Cyprohaptidine
15-Proton Pump inhibitor- Omeprazole
16-DNA Metabolism Inhibitors- Quinacrine (Mepacrine)
17-Spindle Poison- Vinca, Griesofulvin
18-Folic acid synthesis inhibitor- DDS
19-GABA Inhibitor- Sodium Valproate
20-DNA Synthesis Prevention – Nalidixic Acid
21-Prostaglandin Synthesis Inhibition- Oxyphenbutazone, Ibuprofen
22-Mycolic acid synthesis inhibition- INH
23-Folic acid antagonist- MTX, PAS, DDS & Primethamine
24-Desruption of DNA structure- MNZ
25-Inhibition of cell wall synthesis- Beta lactam antibiotics (penicillin)
26-Release of nor epinephrine- Ephedrine
27-Ergosterol Biosnythesis Inhibitors- Clotrimazole, Miconalzole, Ketoconazole

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28-Ach esterase inhibitors- Physostigmine, Neostigmine, Edrophonium, Metrifonate

29-Reverse Transcriptase Inhibitors- Stavudine, zidovudine
30-Inhibition of HIV Protease- Amepranavir
31-DNA Gyrase Inhibitor- Cinoxacin
32-Inhibition of DNA Polymerase-Gossypol
33-NMDA Receptor Antagonist- Amantadine, Ketamine, Dextromethorphan, Memantine &
Nitrous Oxide
34-DNA intercalating agent- Daunorubicin, Doxorubicin, Ellipticin & Ethidium Bromide
35-Antim mitotic agent- Amphethenile
36-Alkylating agent- Thiotepa
37-Alpha receptor antagonist- Phentolamine
38-Beta receptor antagonist- Propanolol, Aplrenolol
39-Alpha receptor agonist- Norepinehrine
40- Beta receptor agonist- Isoproterenol & Salbutamol
41-DNA Adduct Formation- Procarbazine
42-Carbonic anhydrase inhibitor- Acetazolamide
43-Phosphodiestrase Inhibitor- Theophylline
44-Thrombin action prevention- Heparin
45-Xanthine oxidase inhibitor- Allopurinol
46-Cholinergic Blockade- Ipratropium
47-Adenosine Deaminase inhibitor- Crisnatapase
48-Immunomodulation- Imiquimod
49-Amino acid transfer interference- Econazole
50-Mast Cell Stabilization- Ketosifen

MUST DO THIS TABLE IMP FROM JURI

SR NO ORGANISATION LOCATION

1 BCG Vaccine Lab Chennai

2 Central drug testing lab (CDTL) Mumbai

3 Central drug Laboratory (CDL) Kolkata

4 Central Drug Research Institute (CDRI) Lucknow

5 Central Research Institute (CRI) Kasauli

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6 Indian Drug Manufactures Association (IDMA) Mumbai

7 Indian Society of Blood Trensfusion & Immunoheamatology Pune

8 Indian Veterinary Research Institute (IVRI) Izatnagar

9 Central Indian Pharmacoepia Laboratory (CIPL) Ghaziabad

10 National Plasma Fractionation Centre (NPFC) Mumbai

11 National Institute for Communicable Disease (NICD) New Delhi

12 Indian Institute for Virology (IIV) Pune

13 Organization of Pharmaceutical Procedures Mumbai

14 Dabur Research foundaion Ghaziabad

15 Institute of applied man power research New Delhi

16 CD Testing Lab Mumbai

17 Synthetic Drug Plant Hyderabad

18 National Institute of Nutrition (NIN) Hyderabad

19 National Brain Research Institute (NBRI) Manesar (Gurgaon)

IMPORTANT PHARMACOLOGICAL TERMS:

•Antagonism
–The opposition between 2 or more medications ex. narcotics and Naloxone
•Bolus
–A single, often large dose of a drug. Often the initial dose
•Cumulative action
–An increased effect caused by multiple doses of the same drug. Caused by buildup in the
blood.
•Hypersensitivity
–A reaction to a drug that is more profound than expected and which often results in an
exaggerated immune response
•Idiosyncrasy
–A reaction to a drug that is significantly different from what is expected
•Indication
–The medical condition for which the drug has proven therapeutic value.

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•Parenteral
–Any route of administration other than the digestive tract
•Pharmacodynamics
–Study of the mechanisms by which drugs act to produce biochemical or physiological
changes in the body
•Pharmacokinetics
–Study of how drugs enter the body, reach their site of action and are eliminated from the
body.
•Potentiation
–The enhancement of a drug’s effect by another drug
–Eg. Promethazine may enhance the effect of morphine; also alcohol and barbiturates
•Refractory
–The failure of a patient to respond as expected to a certain medication
•Synergism
–The combined action of 2 or more drugs that is greater than the sum of the 2 drugs acting
independently.
•Therapeutic Action
–The intended action of a drug given in an appropriate medical setting
•Therapeutic Threshold
–The minimum amount of a drug that is required to cause the desired response
•Therapeutic Index
–The difference between the therapeutic threshold and the amount of the drug considered to
be toxic
–Often referred to as Safe and Effective range.
•Tolerance
–The decreased sensitivity or response to a drug that occurs after repeated doses
–Increased doses are required to achieve the desired effect
• Untoward Effect
–A side effect of a drug that is harmful to the patient

STERILIZATION OF MEDIA

In almost all cases, once a medium is made, it must be treated to eliminate any
microorganisms contaminating containers, media ingredients, weighing papers, or other

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surfaces that come in contact with the medium. If this is not performed correctly,
contaminates arise during incubation, making microbiological investigations impossible.
Sterilization is defined as the inactivation (or removal) of all life forms (including the pseudo-
life forms, viruses) in a specific area. Culture media must be made sterile without inactivating
nutrients necessary for growth of the microorganism. Equipment and media used in the
microbiology laboratory are most often sterilized using one of the methods outlined below.

Autoclaving - moist heat (121°C) under pressure (15-17 lb/in2)

Mode of action - coagulates proteins
Materials - heat stable items such as most culture media, glass and metal, but not plastics
Oven - dry heat (160°C for several hours)
Mode of action - coagulates proteins
Materials - glass and metals but not liquids nor plastics
Filtration - 0.22 to 0.45 µm pore size
Mode of action - prevents organisms from passing through the filter, but does allow viruses to
pass so therefore not sterilization in true sense.
Materials - Solutions of heat sensitive compounds such as some amino acids, vitamins,
sugars etc.
Radiation - ultraviolet light or gamma rays
Mode of action - damages nucleic acids
Materials - heat sensitive solids such as plastics, however effective on surfaces only
Gas - ethylene oxide
Mode of action - inactivates enzymes
Materials - heat sensitive solids such as some plastics.

Temperature Relationships
Microorganisms as a whole, are able to grow at a tremendous range of temperatures. Bacteria
have been discovered growing near the Galopagos trench (a marine ocean vent) at
temperatures of 110°C and in super-cooled foods as low as -12°C. The temperature range that
a specific microorganism is able to grow at is thought to be limited by the activity of its
enzymes and the fluidity of the membrane. Extreme temperatures either prevent enzymes
from carrying out their reactions quickly enough (at low temperatures) or denature
(inactivate) enzymes (at high temp and sometimes low temperatures). It is also possible that
temperature has its effect by interfering with the fluidity of membranes, too fluid at high

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temperatures, frozen at low temperatures. Overly fluid membranes cannot maintain their
intergrety and leak, frozen membrane cannot perform vital functions such as electron
transport.
Microbes can be classified by their optimum temperature for growth.

Organisms having an optimum of <20°C are termed Psychrophiles.

Those that grow optimally from 20 to 45°C are called Mesophiles.

Microorganisms that have temperature optima of >45°C are termed Thermophiles.

It is possible for an organisms to have an optimum temperature in one classification, but be

capable of growing at temperatures much above or below the optimum. For
example, Bacillus coagulans is capable of growth at mesophillic temperatures, but will also
grow at temperatures of 55-60°C. These organisms are termed facultative thermophiles.
Microorganisms will cease to grow below their optimum temperature, but frequently will
survive in an inert state. In fact refrigeration or freezing of bacteria can have a preservative
effect. Most microorganisms are killed above the optimum temperature

SOME IMPORTANT NOTES FOR GPAT AND NIPER EXAM

Partition Coefficient:
OCTANOL: water partition coefficient often used in formulation development.
Q10 Method of Shelf Life Estimation:
Shelf life estimation
Q10 = e {(Ea/R) [(1/T + 10) – (1/T)]}
Arrhenius Equation: log = k2\k1 = Ea (T2 – T1)\ 2.3 RT1T2

Shelf Life Estimates:

Q10 = [K (T+10)]/KT =e [(Ea /R) ({1/T+10} {1/T}]

Q10 = 2 Lower limit

Q10 = 3 Average, best estimate
Q10 = 4 Upper limit

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t90 Equation for Shelf Life Estimates:

t90 (T2) = t90 (T1)/Q10 (Delta T/10).
Note: A “+” Delta T decreases shelf life and a “-” Delta T increases shelf life.

Sweetening Agents:
 Dextrose
 Mannitol
 Saccharin
 Sorbitol
 Sucrose

Preservative Utilization:
 •Benzoic acid/sodium benzoate
 •Alcohol
 •Phenylmercuric nitrate/acetate
 •Phenol
 •Cresol
 •Chlorobutanol
 •Benzalkonium chloride
 •Methyl paraben/propyl paraben
 •Others
Preservatives may be used alone or in combination to prevent the growth of
microorganisms.

Alcohols
Ethanol is useful as a preservative when it is used as a solvent. It needs a relatively high
concentration (> 10%) to be effective.

Propylene glycol also used as a solvent in oral solutions and topical preparations. It can
function as a preservative in the range of 15 to 30%. It is not volatile like ethanol.

Acids
 Benzoic acid and sorbic acid have low solubility in water.
 They are used in a concentration range from 0.1 % to 0.5%.
 Only the non-ionized form is effective and therefore its use is restricted to
preparations with a pH below 4.5.

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Esters
Parabens are esters (methyl, ethyl, propyl and butyl) of p-hydroxybenzoic acid.
 They are used widely in pharmaceutical products
 They are effective and stable over a pH range of 4 to 8.
 They are employed at concentrations up to about 0.2%.
 Frequently 2 esters are used in combination in the same preparation.
 To achieve a higher total concentration
 To be active against a wider range of microorganisms.

Quaternary Ammonium Compounds

 Benzalkonium chloride is used at a relatively low concentration 0.002 to 0.02%.
 This class of compounds has an optimal activity over the pH range of 4 to 10 and is
quite stable at most temperatures.
 Because of the cationic nature of this type of preservative it is incompatible with
many anionic compounds.

Antioxidants
Vitamins, essential oils & almost all fats and oils can be oxidized.
Oxidation reaction can be initiated by:
1. Heat: maintain oxidizable drugs in a cool place
2. Light: use of light- resistant container
3. Heavy metals (e.g. Fe, Cu): effect of trace metals can be minimized by using citric acid or
ethylenediamine tetraacetic acid (EDTA) i.e. sequestering agent.

Antioxidants as propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite,
ascorbic acid (vit. C) Can be used.

•SWEETENING AGENTS

Sucrose is the most widely used sweetening agent.

Advantages: Colourless, highly water soluble, stable over a wide pH range (4-8), increase the
viscosity, masks both salty and bitter taste, has soothing effect on throat.
Polyhydric alcohols (sorbitol, mannitol and glycerol) possess sweetening power and can be
used for diabetic preparations.
Humectants: such as glycerin and sorbitol (5-20% in MW)

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 Increase the viscosity of the preparation

 Enhance the sweetness of the product
 Improve the preservative qualities of the product.

Surfactants: Non-ionic and anionic surfactants aid in the solubilization of flavors and in the
removal of debris by providing foaming action. Cationic surfactants such as
cetylpyridinium chloride are used for their antimicrobial properties, but these tend to impart
a bitter taste.
Flavours: are used in conjunction with alcohol and humectants to overcome disagreeable
tastes. The principle flavoring agents are peppermint, cinnamon, menthol or methyl
salicylate.
Otic Solutions:
The main classes of drugs used for topical administration to the ear include local anesthetics,
e.g.: benzocaine; antibiotics e.g.; neomycin; and anti-inflammatory agents, e.g.; cortisone.
Polyols (e.g. glycerin or sorbitol) may be added to
- retard crystallization of sucrose or increase the solubility of added ingredients.
Invert sugar
D is more readily fermentable than sucrose
D tend to darken in color
C retard the oxidation of other substances.
The levulose formed during inversion is sweeter than sucrose; therefore the resulting syrup is
sweeter than the original syrup.

When syrup is overheated it caramelizes.

The sucrose in the 66.7% w/w solution must be at least 95% inverted.

MUCILAGES
The official mucilages are thick viscid, adhesive liquids, produced by dispersing gum (acacia
or tragacanth) in water.
Mucilages are used as suspending agents for insoluble substances in liquids; their colloidal
character and viscosity prevent immediate sedimentation.
Synthetic agents e.g. carboxymethylcellulose (CMC) or polyvinyl alcohol are
nonglycogenetic and may be used for diabetic patients.

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ELIXIRS
Are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use.
They are used as flavors and vehicles
E.g. Dexamethasone Elixir USP and Phenobarbital Elixir USP.

COLLODIONS:
Are liquid preparations containing pyroxylin (a nitrocellulose) in a mixture of ethyl ether and
ethanol

Rubefacient
A substance for external application that produces redness of the skin e.g. by causing dilation
of the capillaries and an increase in blood circulation.

Counterirritant
A medicine applied locally to produce superficial inflammation in order to reduce deeper
inflammation.

Effervescent tablet:
contain acid substances (citric and tartaric acids) and carbonates or bicarbonates and
which react rapidly in the presence of water by releasing carbon dioxide.

Oxymels: These are preparations in which the vehicle is a mixture of acetic acid and honey.

Magnesium sulphate: Magnesium cause smooth muscle relaxation secondary to inhibition

of calcium uptake.

Atopy is strongest predisposing factor for developing asthma.

Asthma is a chronic inflammatory disorder of the airways in which many cells &
cellular elements play a role
(Mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, & epithelial cells).
Child-onset asthma
–Associated with Atopy
–IgE directed against common environmental antigens
(House-dust mites, animal proteins, fungi

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–Viral wheezing Infants/children, allergy/allergy history associated with continuing

asthma through childhood.
Leukotriene modifiers:
 Zafirlukast - leukotriene receptor antagonist

 Zileuton - 5-lipoxygenase inhibitor is alternative therapy to low doses of inhaled

steroids/nedocromil/cromolyn. 5-lipoxygenase inhibitor

Long-acting beta2-agonists (LABA)
Beta2-receptors are the predominant receptors in bronchial smooth muscle Stimulate ATP-
cAMP which leads to relaxation of bronchial smooth muscle and inhibition of release of
mediators of immediate hypersensitivity Inhibits release of mast cell mediators such as
histamine, leukotrienes, and prostaglandin-D2. Beta1-receptors are predominant receptors in
heart, but up to 10-50% can be beta2-receptors.
Long-acting beta2-agonists (LABA)
 Salmeterol (Serevent)
 Salmeterol with fluticasone (Advair).
 Albuterol
DRUGS AND SCHEDULE

Schedule I
Drugs in this schedule have a high abuse potential (narcotic and hallucination effects).
Examples are heroin, marijuana.
Schedule II
Drugs in this schedule have a high abuse potential with severe psychic or physical
dependence liability. Included are certain narcotic analgesics, stimulants, and depressant
drugs. Examples are opium, morphine, codeine, hydromorphone, methadone, meperidine,
oxycodone, anileridine, cocaine, amphetamine, methamphetamine, phenmetrazine,
methylphenidate, amobarbital, pentobarbital, secobarbital, methaqualone, and phencyclidine.
Schedule III
Drugs in this schedule have an abuse potential less than those in Schedules I and II and
include compounds containing limited quantities of certain narcotic analgesic drugs, and
other drugs such as barbiturates, glutethimide, methyprylon, and chlorphentemine. Any
suppository dosage form containing amobarbital, secobarbital, or pentobarbital is in this
schedule.

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Schedule IV
Drugs in this schedule have an abuse potential less than those listed in Schedule III and
include such drugs as barbital, phenobarbital, chloral hydrate, ethchlorvynol, meprobabmate,
chlordizepoxide, diazepam, oxazepam, chloroazepate, flurazepam, etc.
Schedule V
Drugs in this schedule have an abuse potential less than those listed in Schedule IV and
consist primarily of preparations containing limited quantities of certain narcotic analgesic
drugs used for antitussive and antidiarrheal purposes.

SOME IMP PONTS FROM PHARMACEUTICS

Creams – semisolid emulsion systems (o/w, w/o) containing more than 10% of water.
Pastes – semisolid dispersion system, where a solid particles (> 25%, e.g. ZnO) are
dispersed in ointments – mostly oleaginous (Petrolatum).

Antioxidants which act by providing electrons and easily available hydrogen atoms that
acceptable more readily by the free radicals (atoms containing one or more unpaired
electrons as molecular oxygen O-O or free hydroxyl group (OH)
Examples of Antioxidants: Na2SO3, NaHSO3, H3PO2 and Ascorbic
In oligeanous preparation –
 Alpha tocopherol,
 BHA (butylhydroxyanisole),
 BHT (butyl hydroxytoluene)
 Ascorbic palmitate.

EXAMPLES:
Epinephrine preparations - Adrenergic - do not use the if it is brown or contains precipitate
Nitroglycerin Tablets - Antianginal - to prevent loss of potency, keep these tablets in the
original container
Paraldehyde - Hypnotic - subject to oxidation to form acetic acid.

POLYMORPHISM:
Important factor on formulation is the crystal or amorphous from of the drug substance.
The amorphous form of a compound is always more soluble than a corresponding crystal form.

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The most widely used methods are hot stage microscopy, thermal analysis, infrared
spectroscopy, and x-ray diffraction.

PROBABLE MODES OF ACTION OF SOME PRESERVATIVES

1. Benzoic acid, boric acid, p-hydroxybenzoates: Denaturation of proteins.

2. Phenols, chlorinated phenolic cmpds: lytic, denaturation action on cytoplasmic
membranes and for chlorinated preservatives, also by oxidation of enzymes
3. Alcohols: lytic and denaturation action on membranes.
Quaternary compounds: Lytic action on membranes.
4. Mercurials: Denaturation of enzymes by combining with thiol (-SH) groups.
Flavoring Agents
*** To mask effectively the unwanted or disagreeable taste of drugs
In general, low molecular weight are salty, like NaCl, KCl, NH4Cl, NaBr and higher
molecular salts are bitter except some lead salts.
Examples: Anise oil, Cinnamon, Peppermint, and Orange.
With organic compounds, an increase in the number of OH group seems to increase the
sweetness of the compound. Sucrose which has 8 OH groups is sweeter
than glycerin which has 3 OH groups.
SWEETENING PHARMACEUTICALS

SACCHARIN = metabolized and excreted by the kidneys virtually unchanged.

CYCLAMATE = metabolized or processed in digestive tract and it’s by product are excreted
by the kidneys.
ASPARTAME = breaks down in the body into three basic components: the amino
acids phenylalanine and aspartic acid, and methanol.

Because of its metabolism to phenylalanine, the use of aspartame by persons with phenylketonuria
(PKU) is discourages, and diet foods and drinks must bear appropriate label warning.
Saccharin and cyclamate were “Generally Recognized as Safe” or what is known as GRAS.

ACESULFAME = is more stable than aspartame at elevated temperature;

It is use in candy, chewing gum, confectionery, and instant coffees and teas.
STEVIA POWDER = Stevia Rebaudiana bertoni.
It is natural, nontoxic, safe, and about 30 times as sweet as cane sugar, or sucrose.

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AESTHETIC VALUE

Liquid preparations - the amount is ranging from 0.0005 to 0.001% depending upon the
colorant and intensity desired Solid or powdered, Compressed Tablets - generally larger
proportion is required (0.1% Ointments, suppositories, opthalmic and parenteral -no
color additives)

DISSOLUTION APPRATUS IP AND USP

APPRATUS IP USP

Apparatus 1 Paddle (37º) Basket (37º)

Apparatus 2 Basket (37º) Paddle (37º)

Apparatus 3 Reciprocating Cylinder (37º) Reciprocating Cylinder (37º)

Apparatus 4 Flow-Through Cell (37 º) Flow-Through Cell (37 º)

Apparatus 5 Paddle over Disk (32º), Paddle over Disk (32º),

Apparatus 6 Cylinder (32º) Cylinder (32º)

Apparatus 7 Reciprocating Holder Reciprocating Holder

SOME IMP DRUG INTREACTION

S.N DRUG INTERACTION EFFECT

Aluminium Hydroxide Gel + Decrease effect of that drug due to

1 Pseudoephedrine increases pH of gastric fluid

2 Ciprofloxacin + Theophyline Increases plasma level of Theophyline

Aminoglycoside + beta- Lactam synergestic effect but if given in same

antibiotics syring it‘s become inactive due to
3
complex formation

4 Cortisone + Ampicillin= Antagonist

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Erythromycin /Clarithromycin/ Increases level of Carbamazapine and

Telrithromycin + Carmazepam/ Phenytoin
5
Phenytoin =

Methotrexate + Sulfamethoxazole Displace from binding site and increases

6 free plasma concentration of drug

7 Amphotericin B + Flucytosine Synergestic effect

Ketoconazole + Amphotericin B Antagonized effect due to decreases

8 ergosterol level

9 Azoles ( including All) + Terbinafine Contraindicated

10 Posconazole + Ergot alkaloid Contraindicate

Cimetidine + Terbinafine increases plasma concentration of

11 Terbinafine

12 Gresiofulvin + Alcohol Potentiate toxicity of alcohol

13 Miconazole+ Warfarin inhibit metabolism of warfarin

14 MAO inhibitors + Pethidine Hyperpyrexia

15 TCA + SSRIs TCA toxicity

GOLD NUMBER & PROTECTION OF COLLOIDS

• Lyophilic sols are more stable than lyophobic sols.

• Lyophobic sols can be easily coagulated by the addition of small quantity of an electrolyte.
• When a lyophilic sol is added to any lyophobic sol, it becomes less sensitive towards
electrolytes. Thus, lyophilic colloids can prevent the coagulation of any lyophobic sol.
“The phenomenon of preventing the coagulation of a lyophobic sol due to the addition of
some lyophilic colloid is called sol protection or protection of colloids.”
• The protecting power of different protective (lyophilic) colloids is different. The efficiency
of any protective colloid is expressed in terms of gold number.

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GOLD NUMBER
Zsigmondy introduced a term called gold number to describe the protective power of
different colloids.
This is defined as, “weight of the dried protective agent in milligrams, which when added to
10 ml of a standard gold sol (0.0053 to 0.0058%) is just sufficient to prevent a colour change
from red to blue on the addition of 1 ml of 10 % sodium chloride solution, is equal to the gold
number of that protective colloid.”
Thus, smaller is the gold number, higher is the protective action of the protective agent.
Protective power ∝ 1/Gold number
HYDROPHILIC SUBSTANCE GOLD NUMBER
Gelatin 0.005 - 0.01
Sodium oleate 0.4 – 1.0
Sodium caseinate 0.01
Gum tragacanth 2
Hamoglobin 0.03 – 0.07
Potato starch 25
Gum arabic 0.15 – 0.25

IMP YEARS LIST: USEFUL FOR GPAT & NIPER JEE

1935 RBI established

1949 RBI Nationalized
2005 RTI ACT
2005 Product Patent In India
1956 Companies Act
1932 Partnership Act
1993 End of GATT era
1997 National Pharmaceutical Pricing Authority (NPPA)
1994 Dolly sheep – First clone
1950 First Planning Commission
1984 Hatch-Waxman Act
1955 SBI nationalized

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2005 IPC constituted

1896 First Olympics
2000 (26 Jan.) Human Genome Revealed
1970 Indian Patents Act
1919 Poison Act
1948 Pharmacy Act
1940 Drug and Cosmetic Act
1930 Dangerous Drug Act
1857 Opium Act
1954 Drug and Magic Remedies Act
1971 Medical Termination of Pregnancy Act (MTP)
1989 First ICH Indian pharmacopoeias:
1955 1st Edition IP
1966 2nd Edition IP
1985 3rd Edition IP
1996 4th Edition IP
2007 5th Edition IP
2010 6th Edition IP
2014 7th Edition IP

LIST OF WELL KNOWN POISONS & ANTIDOTES

POISONING ANTIDOTE USED

Paracetamol N-acetylcysteine
Anticoagulants (warfarin) Vitamin K
Opioids Naloxone
Iron (&other heavy metals) Desferrioxamine, Deferasirox or Deferiprone
Benzodiazepines Flumazenil
Ethylene glycol Ethanol or fomepizole, and thiamine, methanol -
ethanol or fomepizole, and folinic acid
Cyanide Amyl nitrite, Sodium nitrite and Sodium thiosulfate
Organophosphates Atropine and Pralidoxime

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Magnesium Calcium Gluconate

Ca++ Cha. Blockers Vera, Dilti. CCB Calcium Gluconate
Beta-Blockers (Propranolol, Sotalol) Calcium Gluconate and/or Glucagon
Isoniazid Pyridoxine
Atropine Physostigmine
Thallium Prussian blue
Hydrofluoric acid Calcium Gluconate
Anticholinergics Cholinergics (&vice-versa)

SOME IMPORTANT FACTS GPAT NOTES

1. Lipid insoluble and water insoluble drugs are not absorbed from gut.
2. Most of the drugs are weakly acidic are weakly basic because stronger forms has high
ability to form corresponding ions.
3. Most (90%) of drugs absorbed through passive diffusion(non-ionic diffusion)
4. 0% protein binding – Lisinopril
5. 99% protein binding - oxyphenbutazone (metabolite of phenylbutazone)
6. To show an efficient drug action protien binding should be moderate, insufficient protein
binding shows less Vd & high protein binding lessens amount of drug at active site.
7. Extent of binding ----- albumin > acid glycoprotein > lipoprotein > globulins.
8. Drug having less Vd means its not bioavailable.(i.e decresed rate & amount of drug)
9. Bioavailability of Higher to Lower ------- parenteral > oral > rectal > topical.
10. Short acting barbiturates are due its rapid rate of distribution from brain.
11. Only unbounded drug (free form) undergoes metabolism.
12. The unbound drug 1st reaches liver from where it goes to other parts like kidneys
13. Only lipid soluble and non-ionic drugs can enters brain.
14. All orally administerd drugs undergo first pass metabolism.
15. Propanolol & Ca++ channel blockers have extensive first pass metabolism.
16. Mainly metabolism occurs to excrete the drug.
17. Acidic drugs are exerted at basic pH & vice-versa.
18. Absorption, Distribution, Elimination follows 1st order kinetics.
19. Drugs showing 0 order elimination kinetics are asprin, ethanol, phenytoin, Theophyline,
Tolbutamide, phenylbutazone, Warfarin, Heparin, salicylates etc.

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20. Metabolism, Protein binding, carrier mediated transport at saturated conditions,

IV infusion IM implants, osmatic pumps undergo 0 order kinetics i.e rate or process
directly proportional to concentration or amount of reactants.

COUNTRY – CAPITAL – CURRENCY IMP FOR GPAT & NIPER JEE EXAM
COUNTRY – CAPITAL – CURRENCY
1. France – Paris – France
2. Germany – Berlin – Deutsche Mar
3. Greece – Athens – Drachma
4. Hong Kong - Victoria – Dollar
5. India - New Delhi – Rupee
6. Indonesia - Jakarta – Rupiah
7. Iran - Teheran – Rial
8. Iraq - Baghdad – Dinar
9. Ireland – Dublin – Pound
10. Italy - Rome – Lira
11. Japan – Tokyo – Yen
12. Kenya - Nairobi – Shilling
13. Malaysia - Kuala Lumpur – Ringgit
14. Nepal – Kathmandu – Rupee
15. New Zealand - Wellington – Dollar
16. Oman - Muscat – Rial
17. Pakistan – Islamabad – Rupee
18. Qatar – Doha – Riyal
19. Russia - Moscow – Ruble
20. Saudi Arabia – Riyadh – Rial
21. Singapore – Singapore City – Dollar
22. South Africa - Madrid – Rand
23. Spain – Madrid – Peseta
24. Sri Lanka - Colombo – Rupee
25. Sweden - Stockholm – Krona
26. Switzerland – Berne – France
27. Russia – Moscow – Ruble
28. Ukraine – Kiev – Hyrvnia

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29. Azerbaijan – Baku – Ruble

30. Thailand – Bangkok – Baht
31. United Arab Emirates (UAE) – Abu Dhabi – Dirham
32. United Kingdom (UK)-London – Pound Sterling
33. United States of America (US) -Washington – Dollar
34. Yemen – Sana – Rial
35. Zimbabwe -Harare – Dollar
DRUGS BANNED IN INDIA
 Tetracycline liquid oral suspension
 Penicillin skin/eye ointement
 Methaquinone
 Oxytetracycline liquid oral preperations
 Demeclocycline liquid oral preperations
 Rosiglitazone
 Astemizole
 Terfinadine

DIFFERENT TESTS FOR CARBOHYDRATES

Name of test Use

Molisch test reducing sugars

Iodine test Starches

Benedicts reagent test Reducing sugars

Same like Molisch test but reduction carried in mild acidic

Barfords Test medium .to distinguish monosaccharide from disaccharides. -
reducing sugars.

Seliwanoffs Test Ketohexoses

Foulgers Test Ketohexoses

Rapid furfural test Ketohexoses

Osazone Test -

Sucrose hydrolysis test Sucrose

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DIFFERENT TESTS FOR AMINO ACIDS AND PROTEINS

NAME OF TEST USE

Biuret reaction Two peptide linkage
Ninhydrin reaction Alfa amino acids

Xanthoproteic reaction Aromatic amino acids like, Phenylalanine, tyrosine, tryptophan

Milons reaction Phenolic amino acids (tyrosine )

Hopkins kole reaction Indole ring (tryptophan)

Sakaguchi reaction Guanidino group (arginine)

Nitroprusside reaction Sulfahydryl group (cysteine)

Sulfer test Sulfahydryl group (cysteine)

Pauly’s test Imidazole ring (histidine)

Folin coicateau’s test Phenolic group (tyrosine)

DIFFERENT TESTS FOR BIOCHEMICAL CONSTITUENTS OF BODY

NAME OF TEST USE/ DETECTION

Sodium hypobromide test Urea

Specific urease test Urea

Benedicts uric acid test Uric acid

Mureoxide test Uric acid (caffine, Theophyline etc.)

Jaffe’s test Creatinine

Benzatidine test Blood in urine etc.

Rothera test Ketone bodies

Hay’s rest Bile salt

Petterkofer’s test Bile salt

Gmelin test Bile pigments

Fouchets test Bile pigments

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Folin wu method Blood glucose estimation

O-toulidine method Blood glucose estimation

Glucose –oxidase peroxidase (GOD-POD) Blood glucose estimation

Van den Bergh reaction Serum bilirubin

Henry-Caraways method Serum uric acid

Western blot TEST

confirmatory test for AIDS

MECHANISM OF ACTION
1- DNA Dependent RNA Polymerase- Rifampcin
2- RNA Dependent DNA Polymerase- Zidovudine
3-Proetin Synthesis Blocker- Erythromycin, Chloramphenicol & Tetracycline
4-ACE Inhibitor- Captopril
5-Ca Channel Blocker- Nifedipine, Diltiazem
6-COX Inhibitor- Asprin
7-GABA Facilitator- Benzodiazepines
8-Antimetabolites- Methotrexate
9-Loop Diuretics- Frusemide
10-High Ceiling Diuretics- Spironolactone
11-Alteration of bacterial DNA- Choloroquine
12-Inhibition of Viral replication- Amantidine, Acyclovir
13-H1 blocking agent- Mepyramine, Loratadine
14-H2 Blocking agent- Rantidine, Cimetidine, Famotidine, Cyprohaptidine
15-Proton Pump inhibitor- Omeprazole, ALL PRAZOLE
16-DNA Metabolism Inhibitors- Quinacrine (Mepacrine)
17-Spindle Poison- Vinca, Griesofulvin
18-Folic acid synthesis inhibitor- DDS
19-GABA Inhibitor- Sodium Valproate
20-DNA Synthesis Prevention – Nalidixic Acid
21-Prostaglandin Synthesis Inhibition- Oxyphenbutazone, Ibuprofen
22-Mycolic acid synthesis inhibition- INH

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23-Folic acid antagonist- MTX, PAS, DDS & Primethamine

24-Desruption of DNA structure- MNZ
25-Inhibition of cell wall synthesis- Beta lactam antibiotics (Penicillin)
26-Release of nor epinephrine- Ephedrine
27-Ergosterol Biosnythesis Inhibitors- Clotrimazole, Miconalzole, Ketoconazole
28-Ach esterase inhibitors- Physostigmine, Neostigmine, Edrophonium, Metrifonate
29-Reverse Transcriptase Inhibitors- Stavudine, zidovudine
30-Inhibition of HIV Protease- Amepranavir
31-DNA Gyrase Inhibitor- Cinoxacin
32-Inhibition of DNA Polymerase-Gossypol
33-NMDA Receptor Antagonist-Amantadine, Ketamine, Dextromethorphan, Memantine &
Nitrous Oxide
34-DNA intercalating agent- Daunorubicin, Doxorubicin, Ellipticin & Ethidium Bromide
35-Antim mitotic agent- Amphethenile
36-Alkylating agent- Thiotepa
37-Alpha receptor antagonist- Phentolamine
38-Beta receptor antagonist- Propanolol, Aplrenolol
39-Alpha receptor agonist-Norepinehrine
40- Beta receptor agonist- Isoproterenol & Salbutamol
41-DNA Adduct Formation- Procarbazine
42-Carbonic anhydrase inhibitor- Acetazolamide
43-Phosphodiestrase Inhibitor- Theophylline
44-Thrombin action prevention- Heparin
45-Xanthine oxidase inhibitor- Allopurinol
46-Cholinergic Blockade- Ipratropium
47-Adenosine Deaminase inhibitor- Crisnatapase
48-Immunomodulation- Imiquimod
49-Amino acid transfer interference- Econazole
50-Mast Cell Stabilization- Ketosifen

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DRUG & THEIR IMORTANT SIDE EFFECT

1. Grey Baby Syndrome- Chloramphenicol

2. Pin Point Pupil, Straubb's syndrome-Morphine
3. Reyes Syndrome- Asprin
4. Urine Coloration- Rifampcin
5. Frontal Headache- Indomethacin
6. Captopril- Persistant dry cough
7. Bleomycin-Pulmonary fibrosis
8. Vancomycin- Red man syndrome
9. Nicotinic acid- Flush
10. Steven Johnsons syndrome- Allopurinol, Sulphonamides, Itraconazole
11. sulphonamides-kernicterus
12. aminoglycosides-ototoxicity
13. Discolouration of teeth-tetracyclines
14. Doxorubucin & duanorubucin- cardiomyopathy.
15. Chloroquine- Cardiotixicity, retinopathy, discolouration of hair
16. Doxycycline- esophageal ulceration
17. Vincristin & Vinblastin- Neuropathy
18).cyclophosphamide- Alopecia, Pancretitis
19. Cimetidine & Spironolactone- Gynaecomastia
20. Jaurisch hexheimer reaction- Penicillin
21. Blue baby syndrome- Amiodarone
22. Nephrotoxicity- Cisplatin
23. Shake and bake syndrome-Amphotericin B
24. S-Thallidomide-Phocomelia
25. Phenytoin-Gingival hyperplasia
26. Valproic acid-curling of hair
27. Carbamazepine-Aplastic anaemia
28. Anticholinergics-Atropine fever

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MICROSCOPY OF SOME IMPOTANT DRUGS

1-Liquorice- Ulignified Septate fibre

2-Solanacoeus Plants- Anisocytic stomata
3-Rhubarb- Star spots
4-Squill- Ca oxide raphides
5-Cardamom- Clothing of glandular trichome
6-Quillaria- Thin membrane arillus
7-Digitalis- Rhytidomes & Glandular Trichomes
8-Atropa Belladona- Anisocytic Stomata
9-Verbascus Thapsus- Clusters of Ca Oxalate
10-Artemisia- T-Shaped Trichomes
11-Stromanium- Phloem Fibres
12-Nuxvomica – Lignified trichomes
13-Fennel- Reticulate lignified trichomes
14-Coriander- Wavy sclerenchyma
15-Indian Dill- Lateral ridges with vascular bundle
16-Anise- Branched & unbranched vittae
17-Cinnamon- Absence of cork & cortex
18-Ginger- Non Lignified vessels & starch grains, Endodermis with no starch
19-Collapsed Endodermis
20-Caraway-Collapsed Parenchyma
21-Chenopodium-Epidermis with no trichomes
22-Chirata- Stomata on lower surface only with no trichomes
23-Cinchona - Large sclerenchymatous bast cells with medullary ray.
24-Cinnamon- Parenchyma cells with starch.
25-Colchicum- Spiral Ducts, Parenchyma with starch
26- Coriander- Prismatic and aggregate crystals of calcium oxalate
27-Saffron- Trichome of stigma
28-Turmeric- Parenchyma with pasty starch
29-Digitalis- Glandular trichomes
30-Euclyptus- Crystal bearing fiber
31-Gentian- Large reticulate ducts
32-Liquorice- Parenchyma with crystals and starch

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33-Hycyamus- Endosperm tissue with proteid granules and oil.

34-Ipecac- Parenchyma with raphides
35-Mentha- Trichomes, simple, showing cuticular markings (a medium sized trichome).
36-Pilocarpus- Aggregate crystals of calcium oxalate.
37-Podophyllum- Reticulate ducts and tracheids, Spiral duct,
Aggregate crystals of calcium oxalate, Cork
38-Quassia- Medullary ray with starch, large porous duct
39-Rheum- Parenchyma with starch, resin and crystals, reticulate ducts.
40-Senega- Parenchyma with fat, Cork & Porous duct.
41-Senna- Bast of vascular bundles, Crystal bearing fibers from vascular tissue
42-Stromanium- Parenchyma cells of petiole
43-Strophanthus- Endosperm tissue, showing oil and crystals, Outer tissue with granular
proteid matter and starch
44-Tobbaco- Parenchyma (collenchymatous) from midrib, Leaf parenchyma with chlorophyll.
45-Ginger- Parenchyma with starch and one cell with resin
46-Belladona- Tracheids and spiral duct, Leaf parenchyma cells with crystals, Bast Cells,
Porous ducts & Crystal Sand

DRUG OF CHOISE IMP FOR GPAT

1. Paracetamol poisoning - acetyl cysteine
2. Acute bronchial asthma - salbutamol
3. Acute gout - NSAIDS
4. Acute Hyperkalemia - calcium gluconate
5. Severe DIGITALIS toxicity - DIGIBIND
6. Acute migraine - sumatriptan
7. Cheese reaction - Phentolamine
8. Atropine poisoning - physostigmine
9. Cyanide poisoning - Amyl nitrite
10. Benzodiazepine poisoning - flumazenil
11. Cholera - tetracycline
12. KALA-AZAR - Lipozomal amphotericin- B
13. Iron poisoning - Desferrioxamine
14. MRSA - vancomycin
15. VRSA - LINEZOLID

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16. Warfarin Overdose - vitamin-K

17. OCD - fluoxetine
18. Alcohol Poisoning - fomepizole
19. Epilepsy in pregnency - Phenobarbitone
20. Anaphylactic shock - Adrenaline

CANIZZARO REACTION

THE ALDEHIDE DO NO HAVE ALFA HIDROGEN GIVES CANIZARO REACTION IN

PRESENCE OF CONCE. NaOH

2 Molecule of Aldehide + conc. NaOH => ALCOHOL + CARBOXILIC ACID

ONE MOLECULE OF ALDEHIDE GET REDCTION REACTION & PRODUCE

ALCOHOL, OTHER GOT OXIDATION PRODUCE CARBOXILIC ACID

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SOME IMPORTANT TOPICS FOR GPAT FROM TABLET AND CAPSULE

 PICKING AND STICKING

This is when the coating removes a piece of the tablet from the core. Overwetting or
examples or excessive film tackiness causes tablets to stick to each other or to the coating
pan. On drying, at the point of contact, a piece of the film may remain adhered to the pan or
to another tablet, giving a “picked” appearance to the tablet surface and resulting in a small
exposed area of the core. It is caused by over-wetting the tablets, by under-drying, or by poor
tablet quality.

REMEDY: A reduction in the liquid application rate or increase in the drying air temperature
and air volume usually solves this problem. Excessive tackiness may be an indication of a
poor formulation.

 TWINNING
This is the term for two tablets that stick together, and it’s a common problem with capsule
shaped tablets.

REMEDY - Assuming you don’t wish to change the tablet shape, you can solve this problem
by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan
speed. In some cases, it is necessary to modify the design of the tooling by very slightly
changing the radius. The change is almost impossible to see, but it prevents the twinning
problem.

 COLOR VARIATION
This problem can be caused by processing conditions or the formulation. Improper mixing,
uneven spray pattern and insufficient coating may result in color variation. The migration of
soluble dyes, plasticizers and other additives during drying may give the coating a mottled or
spotted appearance.

REMEDY:
1. The use of lake dyes eliminates dye migration.
2. A reformulation with different plasticizers and additives is the best way to solve film
instabilities caused by the ingredients.

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 ORANGE PEEL EFFECT

This refers to a coating texture that resembles the surface of an orange. Inadequate spreading
of the coating solution before drying causes a bumpy or “orange-peel” effect on the coating.
It is usually the result of high atomization pressure in combination with spray rates that are
too high. This also indicates that spreading is impeded by too rapid drying or by high solution
viscosity.

REMEDY: Thinning the solution with additional solvent may correct this problem.

 MOTTLED COLOR
This can happen when the coating solution is improperly prepared, the actual spray rate
differs from the target rate, the tablet cores are cold, or the drying rate is out of specification.

 CAPPING AND LAMINATION

This is when the tablet separates in laminar fashion. Capping is partial or complete separation
of top or bottom crowns of tablet main body. Lamination is separation of a tablet into two or
more distinct layers. Friability test can be used to reveal these problems
The problem stems from improper tablet compression, but it may not reveal itself until you
start coating. How you operate the coating system, however, can exacerbate the problem.

REMEDY: Be careful not to over-dry the tablets in the preheating stage. That can make the
tablets brittle and promote capping.

 ROUGHNESS
A rough or gritty surface is a defect often observed when coating is applied by a spray. Some
of the droplets may dry too rapidly before reaching the tablet bed, resulting in the deposits on
the tablet surface of “spray dried” particles instead of finely divided droplets of coating
solution. Surface roughness also increases with pigment concentration and polymer
concentration in the coating solution.

REMEDY: Moving the nozzle closer to the tablet bed and reducing the degree of
atomization can decrease the roughness due to “spray drying”.

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 HAZING / DULL FILM

This is sometimes called Bloom. It can occur when too high a processing temperature is used
for a particular formulation. Dulling is particularly evident when cellulosic polymers are
applied out of aqueous media at high processing temperatures. It can also occur if the coated
tablets are exposed to high humidity conditions and partial salvation of film results.

 BRIDGING
This occurs when the coating fills in the lettering or logo on the tablet and is typically caused
by improper application of the solution, poor design of the tablet embossing, high coating
viscosity, high percentage of solids in the solution, or improper atomization pressure. During
drying, the film may shrink and pull away from the sharp corners of an intagliation or bisect,
resulting in a “bridging” of the surface. This defect can be so severe that the monogram or
bisect is completely obscured.

REMEDY: Increasing the plasticizer content or changing the plasticizer can decrease the
incidence of bridging.

 FILLING
Filling is caused by applying too much solution, resulting in a thick film that fills and
narrows the monogram or bisect. In addition, if the solution is applied too fast, Overwetting
may cause the liquid to quickly fill and be retained in the monogram.

REMEDY: Judicious monitoring of the fluid application rate and thorough mixing of the
tablets in the pan can prevent filling.

 EROSION
This can be the result of soft or friable tablets (and the pan turning too fast), an over-wetted
tablet surface, inadequate drying, or lack of tablet surface strength.

 PEELING AND FROSTING

This is a defect where the coating peels away from the tablet surface in a sheet. Peeling
indicates that the coating solution did not lock into the tablet surface. This could be due to a
defect in the coating solution, over-wetting, or high moisture content in the tablet core which
prevented the coating to adhering.

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 CHIPPING
This is the result of high pan speed, a friable tablet core, or a coating solution that lacks a
good plasticizer

 BLISTERING
When coated tablets require further drying in ovens, too rapid evaporation of the solvent from
the core and the effect of high temperature on the strength, elasticity and adhesion of the film
may result in blistering.

REMEDY: Milder drying conditions are warranted in this case.

 CRACKING
It occurs if internal stresses in the film exceed the tensile strength of the film.
REMEDY: tensile strength of the film can be increased by Using higher molecular weight
polymers or polymer blends.
TABLET AND CAPSULE MACHINES
1. Rotosort- for filled/unfilled capsule sorting machine and for de-dusting.
2. Rotofill- to fill pellets in hard gelatin capsule
3. Rotoweigh- A high speed capsule weighing machine.
4. Accogel- filling of dry powder in soft gelatin capsule.
5. Accofill- fill exact powder dose in hard gelatin capsule
6. Wurster- for coating.
7. Osaka- capsule filling machine (powder, granules)
8. Zanasi- capsule filling (powder, pellets, tablets)
9. Lily/parke-davis: capsule filling (powder)
10. Farmatic, holfiger & kary-liquid filling in HGC.
11. Erweka- De-dusting and polishing capsule machine.
12. Seidender- Uses a Belt for visual inspection.
13. Vericap 1200- capsule weighing machine.

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PHYTOCHEMICAL SCREENING OF DIFFERENT CLASSES OF

DRUGS IN PHARMACOGNOSY NOTES FOR GPAT
Phytochemical screening is done to identify the nature and type of constituents present in a
drug. This technique is of extreme help when a new drug is being investigated for the chemical
constituents. In phytochemical screening there are both general and specific tests for finding the
nature of chemical constituents in the drug. This topic is very simple and short but contains due
weightage in the GPAT due to its importance in the pharmacognosy. Here I am discussing the
topic in detail stressing on the regions important from the perspective of GPAT.

 GENERAL CHEMICAL TESTS FOR ALKALOIDS:

Alkaloids are tested by the following reagents. Each reagent or test has accuracy and
specificity.
i) Dragendroff’s reagent- This reagent is constituted of Potassium Bismuth Iodide (PBI).
Alkaloids give reddish brown color with the dragendroff’s reagent.
ii) Mayer’s reagent- This reagent is constituted of Potassium Mercuric Iodide (PMI). Alkaloids
give cream color with the Mayer’s reagent. Remember M for Mayer M for Mercuric
iii) Wagner’s reagent- This reagent is constituted of Iodine Potassium Iodide (IPI).
Alkaloids give reddish brown precipitate with the Wagner’s reagent.
iv) Hager’s reagent- This reagent is constitutes of Picric Acid. Alkaloids give yellow
precipitate with the Hager’s reagent.
v) Tannic acid- With tannic acid alkaloids give buff colored precipitate.
vi) Picrolinic acid- Yellow colored precipitate are produced with picrolinic acid.

 CHEMICAL TESTS FOR GLYCOSIDES:

 General test for glycosides- The general test for glycoside is as follows-

Test A- Dissolve the 200 mg drug with sulphuric acid. Then, add 5% NaOH solution for
neutralization. Add Fehling solution A & B to the above mixture. Red color is produced.

Test B- Dissolve the 200 mg drug with sufficient amount of water. Add further water to
dilute the solution. This solution is tested with Fehling solution A & B. Red color is produced
from the reducing sugar present in the drug.
 Compare the red color from the two tests of the drug.
 If the color of test A is more intense than test B; glycoside presence confirmed.

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 CHEMICAL TEST FOR ANTHRAQUINONE GLYCOSIDES-

Brontrager’s test- This test is performed for the O-glycosides. Drug is dissolved in 1ml
H2SO4 and mixture is boiled. Filter the solution, filterate is then mixed with chloroform.
Chloroform layer mixed with ammonia gives rose pink color if O-glycosides are present.

Modified brontrager’s test- This test is performed for the investigation of C-glycosides.
Drug is mixed with H2SO4 and FeCl3. The next procedure is same as for the O-glycosides in
brontrager’s test.

Hydroxy anthraquinones- Drug is mixed with Potassium Hydroxide. If hydroxy

anthraquinones are present red color is present.

 CHEMICAL TEST FOR CARDIAC GLYCOSIDES-

Kedde’s test- Extract the drug with CHCl3. 90% alcohol with 2% 3, 5-dinitrobenzoic acid is
added to the extract. To this mixture 20% NaOH is added. Purple color confirms the
presence of cardiac glycoside.

Keller-killiani test- This test is performed only for the digitoxose sugar moiety. Drug is
extracted with chloroform first. 0.4 ml acetic acid is added then along with FeCl3. After
adding H2SO4 if purple color is produced in the acid layer then presence of digitoxose sugar
confirmed.

Raymond’s test- Reagent used in this test is Methanolic alkali. Violet color confirms the
presence of cardiac glycosides.

Legal’s test- This test is performed by using pyridine and alkaline sodium nitroprusside is
used. Red color is produced if cardiac glycoside is present.

Baljet test- Reagent used in this test is picric acid and sodium picrate. Orange color is
produced in the presence of cardiac glycoside.

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 CHEMICAL TEST OF CYANOGENETIC GLYCOSIDE-

Sodium picrate test- Drug is mixed with dilute H2SO4. After the addition of sodium picrate
red color is produced in the presence of cyanogenetic glycoside.
Mercuric acetate test- After mixing the mercuric acetate with drug. Drug acetate is formed
and mercury is separated out which confirms the presence of cyanogenetic glycoside.

 CHEMICAL TEST FOR STEROIDS & TERPENOIDS:

i) Liberman-Burchard test- Drug is mixed with acetic anhydride. To this mixture con.
Sulfuric acid is added. There forms two layers with browning at the junction. Upper layer
with green color represents steroids whereas lower layer represents terpenoids red color.

ii) Salwoski test- Drug is mixed with con. Sulfuric acid. Upper layer is of steroids which are
red in color and lower yellow colored layer represents trirepenes.

iii) Sulphur powder test- If sulfur is added to the mixture of drug, sulfur sinks down the
mixture.
 CHEMICAL TEST FOR FLAVONOIDS:
i) Shinoda test- Shinoda test is performed by adding magnesium along with the HCl in the
drug mixture. Red/pink/green to blue color confirms the presence of flavonoids.

ii) Alkaline reagent test- As the name suggests, an alkaline reagent is used for this test.
Sodium hydroxide is added to the drug. Yellow color is produced; if on addition of dilute
acid this color disappears then it confirms the presence of flavonoids.

iii) ZnHCl test- Flavonoids give red color with the Zinc hydrochloride.

 E) CHEMICAL TESTS FOR TANNINS:

i) Gold beater’s skin test- This is most common test for tannins. This test is performed on
the membrane of OX. Goldbeater’s skin is first treated with HCl and rinsed with distilled
water. After this, this skin is paced in the solution of drug and rinsed with water. After
addition of 1% FeSO4, brown or black color is produced in the skin due to the presence of
tannins.

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ii) FeCl3 test- Yellow color is produced with FeCl3 in the case of hydrolysable tannins
whereas condensed tannins give green color.

iii) Phenazone test- Sodium phosphate is mixed with drug and filtered. To the filtrate
phenazone is added which produce precipitate if tannins are present.

iv) Gelatin test- Precipitate is produced with gelatin which confirms the presence of tannins.

F) CHEMICAL TESTS FOR VOLATILE OILS:

i) Volatile containing drugs when mixed with alcoholic solution of Sudan III gives red color.
ii) Volatile oil containing crude drugs also produces red color with tincture alkane.

TABLET DOSAGE FORM

Tablet is the most common solid dosage forms prescribed and accepted worldwide. Although
there are various types of tablets available in the market depending upon the size, use and
formulation but the basic excipients used in the formulation of tablet are same everywhere.
 What is tablet?
In simple language, tablet is a solid dosage from comprised of active pharmaceutical
ingredient along with several excipients for attaining the desirable biological and
pharmaceutical properties. From an estimate, two-third of the prescribed medicines in the
world is tablet. Most of the tablets are given through oral route but depending on the need and
patient’s concition it can also be given rectally, vaginally, buccally and sub-lingually.
Size and shape of the tablet also vary according to the formulation and need of the patient.
Some tablets are just of few millimeters while other go up to 1 centimeter. Also, shape of the
tablet can also be either oval, round, capsule shaped etc.
Formulation of the tablet: Different excipients used in the tablet

Beside from the active ingredient, tablet contains various other ingredients like diluents,
binder, disintegrant, glidant and lubricant. Chief role of the excilients in the tablet
formulation is to impart desirable pharmaceutical and biological properties to the tablet. Here
is the detail of the different excipients used in the formulation of the tablet.
 DILUENT
The main role of the diluents in the tablet formulation is to impart bulk to the tablet.
Generally, the active ingredient required in a single tablet ranges from 1 mg to 1000 mg. So,

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it is not possible to make a tablet with such small weight therefore diluent is mixed with the
active compound. Major diluents used in the tablet formulation include-
a) CaCO3- Insoluble in water
b) α-Lactose- Most common, inexpensive and inert
c) Mannitol- Used for chewable tablets
d) Microcrystalline cellulose- Increase disintegrant property also

 DISINTEGRANTS
Disintegrants are used for the purpose of breaking the tablet when introduced in the
biological system. Mainly water and pH of the system are responsible for the disintegration
of the tablet. Tablet after disintegration releases its active constituent into the system which
exerts its pharmacological action. Disintegrants used in the tablet are-
a) Alginic acid/Na Alginate – Used concentration is 2-10% w/v
b) Na carboxy methyl cellulose (Nymcel) - Used concentration is 1-20% w/v
c) Microcrystalline cellulose (Avicel) - Used concentration is 10% w/v
d) Starch - Used concentration is 2-10% w/v

 BINDERS (GRANULATING AGENT)

Binders are used to increase the cohesive forces between the ingredients of the tablet so that
tablet can be compressed easily. The concentration of the binder should be used carefully as it
can greatly influence the properties of the tablet. Binders used in the tablet formulation are:
a) Acacia mucilage (20%) - It gives very hard granules.
b) Gelatin (5-20%)
c) PVP (2-10%) – Used for Non-aqueous granulation
d) Starch (5-10%) - Common binder
e) Tragacanth (20%) – Gives hard granules

 GLIDANTS/FILLER
Glidants are used to enhance the flow properties of the granules or powders so that granules
do not stick with each other. Mainly at present there are only two types of glidants used in the
tablet formulation:
a) Colloidal Silica (0.1-0.5%) – Most common and excellent glidant properties
b) Talc (1-2%)

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 LUBRICANTS
Lubricants are used for the comfortable ejection of the tablet from punching machine without
sticking to the die walls. Lubricants used in the tablet formulation include-
a) Stearic acid
b) Liquid Paraffin (5%)
c) Na Benzoate (5%)
d) Na Lauryl sulphate (0.5-5%)

(For tablet and capsule chapter LACHMAN is the best book for GPAT so also refer the
LACHMAN once along with this study material)

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MICROBIOLOGY
 Control of microorganisms
Reduction in numbers and / or activity of the total Achieved by
• Physical agents
• Chemical agents
• Chemotherapeutic agents

 Antimicrobial action is influenced by some factors:

• Environment: Effectiveness of heat is greater in presence of water, acid than in alkali,
consistency of the material (aqueous or viscous), and presence of organic matter.
• Kinds of microorganisms: Growing vegetative cells more susceptible than spore forms,
bacterial spores most resistant of all living organisms.
• Physiological state of cells: Young actively metabolizing cells more susceptible than old,
dormant cells.

 Mode of action of antimicrobial agents:

• Damage to the cell wall or inhibition of cell wall synthesis
• Alteration of the permeability of the cytoplasmic membrane
• Alteration of the physical or chemical state of proteins and nucleic acids
• Inhibition of enzyme action
• Inhibition of protein or nucleic acid synthesis

 Control by Physical agents:

• High temperature
• Low temperature
• Desication : Time of survival of microorganisms after desiccation depends upon factors –
kind of microorganisms, material on which the organisms are dried, completeness of drying
process, physical conditions to which the dried organisms are exposed – light, temperature,
humidity..
• Osmotic pressure
• Radiations – Ionising radiations: knock out electrons from molecules and ionize them
forming hydrogen radicals, hydroxyl radicals, peroxides.
• Non-ionising radiations: less energetic, absorbed specifically by different compounds
causing excitation of their electrons and raise them to higher energy levels.

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• UV radiations are absorbed most specifically by nucleic acids – pyrimidine dimers thus
inhibiting DNA replication and resulting mutations.
• Filters – HEPA (high efficiency particulate air) filters.

Control by Chemical agents

General terms for use with various chemical agents of control:
• Sterilization: is a process in which all viable life forms are either killed or removed.
• Disinfectant: kills growing forms not necessarily the spores of disease producing organisms
• Disinfection: Process of killing infectious agents
• Antiseptic: that opposes sepsis. Usually associated with substances applied to the body
• Sanitizer: that reduces the microbial population to safe levels. Applied to equipment and
utensils used in food industries, restaurants etc.
• Germicide (microbicide): that kills vegetative forms but not necessarily the spores of
germs/microorganisms.
• Bactericide: that kills bacteria
• Bacteriostatic: A condition in which the growth of bacteria is prevented.
• Chemotherapeutic agents: used to treat infections.

Major groups of chemical antimicrobial agents:

Phenols and phenolic compounds:
Phenol was the first disinfectant used in 1880 by Joseph Lister to reduce the infection of
surgical incisions. Used as a standard against which other disinfectants are compared to
determine their antimicrobial activity. Cresol, phenyl phenol etc. are very effective
disinfectants. A 5% solution of phenol rapidly kills the vegetative cells of microorganisms.
• Mode of action:
Precipitation of proteins, inactivation of enzymes, leakage of amino acids from cells.
Phenol coefficient technique: Test organisms are Salmonella typhi or Staphylococcus
aureus. It is calculated by dividing the greatest dilution of the disinfectant killing the test
organism in 10 min but not in 5 min with the greatest dilution of the phenol showing the same
result.
Alcohols: Ethyl alcohol in concentrations between 50 and 90% is effective against
vegetative or non-spore forming cells. Methyl alcohol is less bactericidal, higher alcohols –
propyl, butyl, amyl are more germicidal than ethyl alcohol but since the alcohols higher than
propyl are not miscible with water, they are not commonly used in disinfectants.

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• Mode of action: Protein denaturants, also damage the lipid complex in cell membrane.
Halogens:
Iodine is one of the oldest and most effective germicidal agents.
Tincture of iodine. Also used in the form of substances – iodophores –
Mixtures of iodine with surface-active agents – polyvinylpyrrolidone (PVP).
• Mode of action: Oxidises and inactivates essential metabolic compounds – Proteins with
sulfhydryl groups.
• Chlorine and chlorine compounds: Chlorine gas, hypochlorites, chloramines.
• Mode of action: when chlorine is added in water it forms hypochlorous acid which is
further decomposed to form nascent oxygen. Nascent oxygen being a strong oxidizing agent
denatures major cellular constituents. Chlorine can also combine directly with proteins of cell
membranes and enzymes.
Cl2 + H2O = HCl + HClO (hypochlorous acid)
HClO = HCl + O
 Heavy metals and their compounds:
Mercury, silver, copper. By combining with cellular proteins especially containing sulfhydryl
groups and inactivating them.
 Dyes:
• Triphenylmethane dyes - malachite green, brilliant green, crystal violet.
Gram +ve bacteria more susceptible than gram –ve. Interfere with cellular oxidation
processes.
• Acridine dyes – acriflavine, tryptoflavine. Selective inhibition against staphylococci and
gonococci.
Synthetic detergents:
Detergents are wetting agents, surface tension depressants.
• Anionic detergents – those with detergent property resident in the anion
Soap, Sodium lauryl sulphate (SLS).
• Cationic detergents – those with detergent property resident in cation
Cetylpyridinium chloride. Cationic detergents are more germicidal than anionic compounds.
• Quaternary ammonium compounds: Most of germicidal cationic-detergent
 Compounds are quaternary ammonium salts in which R1, R2, R3 and R4 groups are
 Carbon groups linked to the nitrogen atom.
 The bactericidal power is high againt Gram+ve bacteria.
Mode of action: denaturation of proteins, interference with glycolysis and Membrane damage.

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Aldehydes:
Most effective are formaldehyde and gluteraldehyde. Highly reactive chemicals – combine
readily with vital nitrogen compounds – proteins, nucleic acids.

Gaseous agents:
Ethylene oxide – powerful sterilizing agent – liquid at <10.8oC – highly flammable.
• Mode of action – Alkylation reactions with organic compounds – enzymes and proteins.

Antibiotics and other chemotherapeutic agents:

• Inhibition of cell wall synthesis
• Damage to cytoplasmic membrane
• Inhibition of nucleic acid and protein synthesis
• Inhibition of specific enzyme systems

• Inhibition of cell wall synthesis: Penicillins, ampicillin, cephalosporins – interfere with

final stages of Peptidoglycan synthesis – inhibit transpeptidase reaction – cross-linking of the
two linear polymers.
Cycloserine, vancomycin - inhibits the enzymes involved in the synthesis of pentapeptide side chains.
• Damage to cytoplasmic membrane: Polymyxins, Gramicidins, Tyrocidines – act on
membrane having sterols – fungi and animal cells but not bacteria.
• Inhibition of nucleic acid and protein synthesis: Streptomycin, tetracycline – interfere
with binding of 30S ribosomes, chloramphenicol, erythromycin - binds with 50s ribosome.
• Inhibition of specific enzyme systems – Sulfonamides
Antifungal antibiotics – Nystatin, Griseofulvin
Synthetic chemotherapeutic agents: Nitrofurans – both g+ve and g-ve bacteria,
Nalidixic acid – Inhibition of DNA synthesis in g-ve bacteria.

 CONTROL OF MICROORGANISMS IN FOODS

Aseptic handling
High Temperature – Boiling, Steam under pressure, Pasteurization, Sterilization,
Aseptic processing
Low Temperature – Refrigeration, Freezing,
Dehydration
Osmotic pressure – In concentrated sugar, brine

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Chemicals – Organic acids, SO2, substances developing during food processing, substances
contributed by microbial activity (acids)

Radiations – Ionizing radiations, non-ionizing radiations

High Temperature: One of the safest and most reliable methods. Steam under pressure
cooker, most effective as it destroys all vegetative cells and spores.

Canning – 100oC for high acid foods, 121oC for low acid foods.

Pasteurization: LTH T– 145oF (62.8oC) for 30 min, HTST – 161oF (71.7oC) for 15 sec.
This destroys all yeasts, Molds, gm-ve bacteria and most gram+ve bacteria.
Most heat resistant pathogen Coxiella Burnetti is also killed.
Sterilization: UHT -140-150oC for few seconds.
To understand thermal destruction of microorganisms for use in Food Preservation it is
necessary to understand certain basic concepts:
Thermal Death Time (TDT): Time necessary to destroy a given population of
microorganisms at a specified time.
Thermal Death Point (TDP): Temperature necessary to destroy a given population of
microorganisms in a fixed time, usually 10 min.
Decimal reduction Time (D Value): Time necessary to destroy 90% of the organisms at a
particular temperature.
Z Value: Temperature in oF required to vary D value by 90%.
D Value: Indicates resistance of microorganisms of to a specified temperature.
Z Value Indicates relative resistance to different temperatures.
Z value is used to construct equivalent thermal processes.
At 220oF, D value = 113 min
At 203.5oF, D value = 1130 min (If Z value is 17.5 oF)
At 237.5oF, D value = 11.3 min (If Z value is 17.5 oF)

Aseptic Packaging: In traditional canning methods non-sterile food is placed in a non-sterile

metal/glass container followed by container closure and sterilization.
In aseptic packaging sterile food is placed in a sterile container under aseptic conditions and
sealed under aseptic conditions.

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Low temperature: Activities of spoilage organisms are lowered or stopped.

Dehydration: Drying reduces the aw and thus prevents the growth of microorganisms.

Osmotic pressure: NaCl and sugars exert drying effect – Plasmolysis – death.

Halodurics, halophiles, Osmophiles tolerate the high osmotic pressure.

Direct antimicrobials:
Benzoic acid and parabens:
C6H5COOH and its sodium salt –
C7H5NaO2 along with esters of p-Hydroxybenzoic acid (Parabens).
Antimicrobial activity of benzoate is affected by pH – Greatest activity at low pH –
Ineffective at neutral pH.

ANTIMICROBIAL ACTIVITY RESIDES IN UN-DISSOCIATED MOLECULE

 At pH 4.0 60% compound is un-dissociated.
 At pH 6.0 only 1.5% compound is un-dissociated.
Effective against yeasts and molds.
Generally employed in high acid foods – Apple juice, Soft drinks, Tomato ketchup and
Salads.
Max permissible limit is 0.1%
Common permissible parabens are heptyl-. Methyl-, propyl-, butyl-, ethyl-,
Parabens less sensitive to pH than benzoate – effective upto pH 8.0
Both benzoate, and parabens block oxidation of glucose to pyruvic acid.
Also inhibit uptake of substrate molecules.

SORBIC ACID:
CH3CH=CHCH+CHCOOH – usually employed as Ca, Na or K salt. Permissible limit is
0.2%
Like benzoate also active in acid foods than neutral foods
Generally in-effective at pH >6.5.
 At pH 4.0, 86% un-dissociated
 At pH 6.0, 6% compound is un-dissociated

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Generally effective against molds and yeasts but also to certain bacteria.
Generally used in bakery products, cheese, fruit juices, beverages, salad dressings.
Inhibits dehydrogenase enzyme system.
Also inhibition of cellular uptake of substrate molecules – amino acids, phosphate, organic acids.

PROPIONIC ACID:
CH3CH2COOH as Ca and Na salts.
Mainly a mold inhibitor – used in breads, cakes, cheese.
At pH 4.0 88% is un-dissociated
At pH 6.0 6.7% is un-dissociated
Inhibits cellular uptake of substrate molecules

SULPHUR DIOXIDE AND SULPHITES:

SO2, Na or K salts of SO3 (sulphite), HSO3 (Bisulphite), S2O5 (metabisulphite).
Generally effective againt bacteria
Aerobes more sensitive than anaerobes
More active at acidic pH
SO2 < pH 3.0. HSO3 at pH 3.0-5.0, SO3 > pH 6.0.
At higher concentration yeasts and molds are also inhibited.
Permissible limit is 100-200 ppm
Effect is due to reducing power – reduces the O2 tension to a point at which aerobes are not
able to grow. Also act on enzyme systems – enzyme poison – generally act on disulphide
bonds.
Also used in dried foods to prevent enzymatic browning.

NITRITES AND NITRATES:

Many bacteria are capable of utilizing nitrate as electron acceptor which is reduced to nitrite
highly reactive and capable of serving both reducing and oxidizing agent.
Under acidic conditions it ionizes to form nitrous acid (HONO) – further decomposes to give
nitric oxide (NO) – capable of reacting with catalase, peroxidases, and cytochromes thus
inhibiting aerobic bacteria.

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1. What is Regulatory Affairs?

Ans-Regulatory Affairs in a Pharmaceutical industry, is a profession which acts as the
interface between the pharmaceutical industry and Drug Regulatory authorities across the
world. It is mainly involved in the registration of the drug products in respective countries
prior to their marketing.

2. What are the goals of Regulatory Affairs Professionals?

Ans- Protection of human health Ensuring safety, efficacy and quality of drugs Ensuring
appropriateness and accuracy of product information

3. What are the Roles of Regulatory Affairs professionals?

Ans- Act as a liaison with regulatory agencies Preparation of organized and scientifically
valid NDA, ANDA,INDA ,MAA,DMF submissions Ensure adherence and compliance with
all the applicable cGMP, ICH, GCP, GLP guidelines, regulations and laws Providing
expertise and regulatory intelligence in translating regulatory requirements into practical
workable plans Advising the companies on regulatory aspects and climate that would affect
their proposed activities Apart from the above main roles, there are various other roles which
Regulatory Affairs professionals play.

4. What is an Investigational New Drug (IND) application?

Ans- It is an application which is filed with FDA to get approval for legally testing an
experimental drug on human subjects in the USA

5. What is a New Drug Application?

Ans- the NDA is the vehicle through which drug sponsors formally propose that the FDA
approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during
the animal studies and human clinical trials of an Investigational new drug become part of the
NDA In simple words, “It is an application which is filed with FDA to market a new
Pharmaceutical for sale in USA”

6. What is an Abbreviated New Drug Application (ANDA)?

Ans- It is an application filed with FDA, for a U.S. generic drug approval for an existing
licensed medication or approved drug. In simple words, “It is an application for the approval
of Generic Drugs “

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7. What is a Generic Drug Product?

Ans- A generic drug product is the one that is comparable to an innovator drug product in
dosage form, strength, route of administration, quality, performance characteristics and
intended use.

8. What is a DMF?
Ans- A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA)
that may be used to provide confidential detailed information about facilities, processes, or
articles used in the manufacturing, processing, packaging, and storing of one or more human
drugs.Important facts regarding DMFs It is submitted to FDA to provide confidential
informationIts submission is not required by law or regulationsIt is neither approved nor
disapprovedIt is filed with FDA to support NDA, IND, ANDA another DMF or amendments
and supplements to any of theseIt is provided for in the 21 CFR (Code of Federal
Regulations) 314. 420It is not required when applicant references its own information

9. What are the types of DMF’s?

Ans-Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel (No longer
accepted by FDA) Type II: Drug Substance, Drug Substance Intermediate, and Material Used
in Their Preparation, or Drug Product Type III: Packaging Material Type IV: Excipient,
Colorant, Flavour, Essence, or Material Used in Their Preparation Type V: FDA Accepted
Reference Information (FDA discourages its use)

10. What is a 505 (b) (2) application?

Ans- 505 (b)(2) application is a type of NDA for which one or more investigations relied on
by applicant for approval were not conducted by/for applicant and for which applicant has not
obtained a right of reference.

11. What kind of application can be submitted as a 505(b) (2) application?

Ans- New chemical entity (NCE)/new molecular entity (NME) Changes to previously
approved drugs

12. What are the examples of changes to approved drug products for which 505(b) (2)
application should be submitted?
 Ans- Change in dosage form.

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 Change in strength
 Change in route of administration Substitution of an active ingredient in a formulation
product
 Change in formulation
 Change in dosing regimen
 Change in active ingredient new combination Product
 New indication
 Change from prescription indication to OTC indication
 Naturally derived or recombinant active ingredient
 Bioequivalence

13. What are the chemical classification codes for NDA?

 Number Meaning
 New molecular entity (NME)
 New ester, new salt, or other monovalent derivative
 New formulation
 New combination
 New manufacturer
 New indication
 Drug already marketed, but without an approved NDA
 OTC (over-the-counter) switch

14. What are the differences between NDA and 505 (b) (2) application?
Ans- S.No.New Drug Application (NDA) 505 (b) (2) Application
 All investigations relied on by applicant for approval were conducted by/for applicant
and for which applicant has right of reference One or more investigation relied on by
applicant for approval were not conducted by/for applicant and for which applicant
has not obtained a right of reference
 Generally, filed for newly invented pharmaceuticals. Generally, filed for new dosage
form, new route of administration, new indication etc for all already approved
pharmaceutical. Note: 505 (b) (2) application is a type of NDA.

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15. What is a Marketing Authorization Application?

Ans- It is an application filed with the relevant authority in the Europe (typically, the UK's
MHRA or the EMA’s Committee for Medicinal Products for Human Use (CHMP)) to market
a drug or medicine. As per UK’s MHRA-Applications for new active substances are
described as 'full applications’. Applications for medicines containing existing active
substances are described as 'abbreviated’ or ‘abridged applications’.

16. What is an ASMF?

Ans-Active substance master file is a submission which is made to EMA, MHRA or any
other Drug Regulatory Authority in Europe to provide confidential intellectual property or
'know-how' of the manufacturer of the active substance. In simple words, “It is a submission
made to European Drug regulatory agencies on the confidential information of Active
Substance or Active pharmaceutical Ingredient (API)”.

17. What are the types of active substances for which ASMFs are submitted?
Ans-New active substances existing active substances not included in the European
Pharmacopoeia (Ph. Eur.) or the pharmacopoeia of an EU Member StatePharmacopeial active
substances included in the Ph. Eur. or in the pharmacopoeia of an EU Member State

18. What is the difference between DMF and ASMF (with respect to submission)?
Ans-ASMF is submitted as Applicant’s Part (Open Part) and Restricted Part (Closed Part)
there isn’t any differentiation of DMF’s into parts

19. What is ICH?

Ans-International Conference on Harmonisation of Technical Requirements for Registration
of Pharmaceuticals for Human Use (ICH): is a project that brings together the regulatory
authorities of Europe, Japan and the United States and experts from the pharmaceutical
industry in the three regions to discuss scientific and technical aspects of pharmaceutical
product registration.

20. What is CTD?

Ans-The Common Technical Document (CTD) is a set of specification for application
dossier, for the registration of Medicines and designed to be used across Europe, Japan and
the United States. Quality, Safety and Efficacy information is assembled in a common format

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through CTD .The CTD is maintained by the International Conference on Harmonisation of

Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).CTD
format for submission of drug registration applications/dossiers is widely accepted by
regulatory authorities of other countries too like Canada, Australia etc.

21. What are the ICH guidelines to be referred for preparation of registration
dossiers/applications of medicines (With respect to format and contents in each
module)?
 M4 Guideline
 M4Q Guideline
 M4S Guideline
 M4E Guideline

22. What are the modules in CTD?

Ans- the Common Technical Document is divided into five modules:
 Module 1. Administrative information and prescribing information
 Module 2. Common Technical Document summaries
(Overview and summary of modules 3 to 5)
 Module 3. Quality
 Module 4. Nonclinical Study Reports (toxicology studies)
 Module 5. Clinical Study Reports (clinical studies)

22. What is Orange Book?

Ans-It is the commonly used name for the book “Approved Drug Products Equivalence
Evaluations”, which is published by USFDA.It contains the list of drug products, approved
on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under
the Federal Food, Drug, and Cosmetic Act.

23. What is Hatch-Waxman act?

Ans-It is the popular name for Drug Price Competition and Patent Term Restoration Act,
1984. It is considered as the landmark legislation which established the modern system of
generic drugs in USA. Hatch-Waxman amendment of the federal food, drug and cosmetics
act established the process by which, would be marketers of generic drugs can file

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Abbreviated New Drug Application (ANDA) to seek FDA approval of generic drugs.
Paragraph IV of the act, allows 180 day exclusivity to companies that are the "first-to-file" an
ANDA against holders of patents for branded counterparts.In simple words “Hatch-Waxman
act is the amendment to Federal, Food, Drug and Cosmetics act which established the modern
system of approval of generics ”

24. What are the patent certifications under Hatch-Waxman act?

Ans-As per the Hatch and Waxman act, generic drug and 505 (b) (2) applicants should
include certifications in their applications for each patent listed in the “Orange Book” for the
innovator drug. This certification must state one of the following:(I) that the required patent
information relating to such patent has not been filed (Para I certification);(II) that such
patent has expired (Para II certification);(III) that the patent will expire on a particular date
(Para III certification); or(IV) that such patent is invalid or will not be infringed by the drug,
for which approval is being sought(Para IV certification).A certification under paragraph I or
II permits the ANDA to be approved immediately, if it is otherwise eligible. A certification
under paragraph III indicates that the ANDA may be approved when the patent expires.

25. What is meant by 180 day exclusivity?

Ans-The Hatch-Waxman Amendments provide an incentive of 180 days of market
exclusivity to the “first” generic applicant who challenges a listed patent by filing a paragraph
IV certification and thereby runs the risk of having to defend a patent infringement suit.180
Day Exclusivity could be granted to more than one applicant.
The recent example is- 180 day exclusivity was granted to Ranbaxy and Watson Laboratories
for marketing generic version of Lipitor (Atorvastatin calcium).

26. What are the procedures for Approval of Drug in EU?

 Centralised Procedure (CP)
 Decentralised Procedure (DCP)
 Mutual Recognition Procedure (MRP)
 National Procedure (NP)

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27. What is the Full form of abbreviation, CEP?

Certificate of Suitability to the monographs of the European Pharmacopoeia (or) Certificate
of suitability of monographs of the European Pharmacopoeia (or) Certification of suitability
of European Pharmacopoeia monographs
It is also informally referred to as Certificate of Suitability (COS)

28. What is a CEP?

Ans. It is the certificate which is issued by Certification of Substances Division of European
Directorate for the Quality of Medicines (EDQM), when the manufacturer of a substance
provides proof that the quality of the substance is suitably controlled by the relevant
monographs of the European Pharmacopoeia.

29. What are the recently approved new Drugs by FDA (Under NDA Chemical Type 1)?
AS. NO. NDA NAME OF DRUG NAME OF ACTIVE INGREDIENT COMPANY
1203188 KALYDECOIVACAFT OR VERTEX PHARMS
2203388 ERIVEDGE VISMODEGIBGENEN TECH
3202324 INLYTA AXITINIBPFIZER
4202833 PICATOINGENOL MEBUTATELEO PHARMA AS
5202514 ZIOPTAN TAFLUPROSTMERCK SHARP DOHME
6021746 SURFAXINLUCINACTANT DISCOVERY LABORATORIES INC30.

FULL FORM
NDA New Drug Application

ANDA Abbreviated New Drug application

IND Investigational New Drug Application

DMF Drug Master File

ASMF Active Substance Master File

MAA Marketing Authorisation Application

Certificate of Suitability to the monographs of the European

CEP
Pharmacopoeia

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The International Conference on Harmonisation of technical

ICH
requirements for registration of Pharmaceuticals for human use.

Common technical document for the registration of pharmaceuticals

CTD
for human use.

AP Applicant’s Part

RP Restricted Part

OP Open Part

CP Closed Part

NME New Molecular Entity

NCE New Chemical Entity

SmPC Summary of Product Characteristics

PL Packaging Leaflet

RMS Reference Member State

CMS Concerned Member State

CHMP The Committee for Medicinal Products for Human Use

CPMP Committee for Proprietary Medicinal Products

CVMP Committee for Medicinal Products for Veterinary Use

SUPAC Scale-up and post approval changes

BACPAC Bulk Active Chemicals Post approval Changes

cGMP Current good Manufacturing Practice

GCP Good clinical Practice

GLP Good Laboratory Practice

31. Well known Drug Regulatory Agencies across the world-

NAME OF COUNTRY REGULATORY AGENCIES
United States of America United States Food and Drug Administration (USFDA)
Medicines and Healthcare products Regulatory Agency
United Kingdom
(MHRA)

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European Union European Medicines Agency (EMA)

European Union European Directorate for the Quality of Medicines (EDQM)

Australia Therapeutic Goods Administration (TGA)

Therapeutic Products Directorate (TPD) in Health Product

Canada
and food branch (HPFB) of Health Canada (HC)

Japan Pharmaceutical and Medical Devices Agency (PMDA)

Agence Francaise de Securite Sanitaire des Produits de Sante

France (AFSSAPS)Translated into English as- French Agency for the
Safety of Health Products

Bundesinstitut für Arzneimittel und Medizinprodukte,

Germany (BfArM) Tanslated into English as- Federal Institute for
Drugs and Medical Devices
Agência Nacional de Vigilância Sanitária (ANVISA)
Brazil Tanslated into English as- The National Health Surveillance
Agency

Drugs Controller General of India (DCGI) who heads Central

India
Drugs Standard Control Organisation (CDSCO)

Switzerland Swiss Agency for Therapeutic Products (SWISSMEDIC)

Singapore Health Sciences Authority (HSA)

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D & C ACT (1940) LIST OF AMENDING ACTS AND ADAPTATION ORDER

1. The Repealing and Amending Act, 1949 (40 of 1949).
2. The Adaptation of Laws Order, 1950.
3. The Part B States (Laws) Act, 1951 (3 of 1951)
4. The Drugs (Amendment) Act, 1955 (11 of 1955)
5. The Drugs (Amendment) Act, 1960 (35 of 1960)
6. The Drugs (Amendment) Act, 1962 (21 of 1962)
7. The Drugs and Cosmetics (Amendment) Act, 1964 (13 of 1964)
8. The Drugs and Cosmetics (Amendment) Act, 1972 (19 of 1972).
9. The Drugs and Cosmetics (Amendment) Act, 1982 (68 of 1982)
10. The Drugs and Cosmetics (Amendment) Act, 1986 (71 of 1986)
11. The Drugs and Cosmetics (Amendment) Act, 1995 (22 of 1995)

THE DRUGS AND COSMETICS ACT, 1940

ARRANGEMENT OF SECTIONS
CHAPTER I
INTRODUCTORY
SECTIONS

1. Short title, extent and commencement.

2. Application of other laws not barred.
3. Definitions
3A. Construction of references to any law not in force or any functionary not in existence in
the State of Jammu and Kashmir.
4. Presumption as to poisonous substances.

CHAPTER II
THE DRUGS TECHNICAL ADVISORY BOARD, THE CENTRAL DRUGS
LABORTORY AND THE DRUGS CONSULTATIVE COMMITTEE

5. The Drugs Technical Advisory Board.

6. The Central Drugs Laboratory.
7. The Drugs Consultative Committee.
7A. Section 5 and 7 not to apply Ayurvedic, Siddha or Unani drugs.

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CHAPTER III
IMPORT OF DRUGS AND COSMETICS
8. Standards of quality
9. Misbranded drugs
9A. Adulterated drugs
9B. Spurious drugs.
9C. Misbranded cosmetics.
9D. Spurious cosmetics
10 Prohibition of import of certain drugs or cosmetics.
10A. Power of Central Government to prohibit import of drugs and cosmetics in public interest.
11. Application of law relating to sea customs and powers of Customs officers.
12 Power of Central Government to make rules.
13 Offences.
14 Confiscation
15. Jurisdiction

CHAPTER IV
MANUFACTURE, SALE AND DISTRIBUTION OF DRUGS AND COSMETICS
SECTIONS
16. Standards of quality.
17. Misbranded drugs.
17A. Adulterated drugs.
17B. Spurious drugs.
17C. Misbranded cosmetics.
17D. Spurious cosmetics.
18. Prohibition of manufacture and sale of certain drugs and cosmetics.
18A. Disclosure of the name of the manufacturer, etc.
18B. Maintenance of records and furnishing of information.
19. Pleas .
20. Government Analysts.
21. Inspectors.
22. Powers of Inspectors.
23. Procedure of Inspectors.
24. Persons bound to disclose place where drugs or cosmetics are manufactured or kept.

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25. Reports of Government Analysts.

26. Purchaser of drug or cosmetic enabled to obtain test or analysis.
26A. Power of Central Government to prohibit manufacture etc. of drug and cosmetic in
public interest.
27. Penalty for manufacture, sale, etc., of drugs in contravention of this Chapter.
27A. Penalty for manufacture, sale, etc., of cosmetics in contravention of this Chapter.
28. Penalty for non-disclosure of the name of the manufacturer, etc.
28A. Penalty for not keeping documents, etc., and for non-disclosure of information.
28B Penalty for manufacture, etc. of drugs or cosmetics in contravention of section 26A.
29. Penalty for use of Government Analyst’s report for advertising.
30. Penalty for subsequent offences.
31. Confiscation.
31A. Application of provisions to Government departments.
32. Cognizance of offences.
32A. Power of Court to implead the manufacturer, etc.
33. Power of Central Government to make rules .
33A. Chapter not to apply to Ayurvedic, Siddha or Unani drugs.

CHAPTER IVA
PROVISIONS RELATING TO AYURVEDIC SIDDHA AND UNANI DRUGS
SECTIONS
33B. Application of Chapter IVA.
33C. Ayurvedic, Siddha and Unani Drugs Technical Advisory Board.
33D. The Ayurvedic, Siddha and Unani Drugs Consultative Committee.
33E. Misbranded drugs.
33EE. Adulterated drugs.
33EEA. Spurious drugs.
33EEB. Regulation of manufacture for sale of Ayurvedic, Siddha and Unani drugs.
33EEC. Prohibition of manufacture and sale of certain Ayurvedic, Siddha and Unani drugs.
33EED. Power of Central Government to prohibit manufacture etc., of
Ayurvedic, Siddha or Unani drugs in public interest.
33F. Government Analysts.
33G. Inspectors .
33H. Application of provisions of sections 22, 23, 24 and 25.

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33I. Penalty for manufacture, sale, etc., of Ayurvedic, Siddha or Unani drugs in
contravention of this Chapter.
33J. Penalty for subsequent offences.
33K. Confiscation.
33L. Application of provisions to Government departments.
33M. Cognizance of offences.
33N. Power of Central Government to make rules.
33O. Power to amend First Schedule.

CHAPTER V MISCELLANEOUS
33P. Power to give directions.
34. Offences by companies.
34A. Offences by Government departments.
34AA. Penalty vexatious search or seizure.
35. Publication of sentences passed under this Act.
36. Magistrate’s power to impose enhanced penalties.
36A. Certain offences to be tried summarily.
37. Protection of action taken in good faith.
38. Rules to be laid before Parliament.

YEAR AND ACT

1970 Indian Patents Act

1919 Poison Act
1948 Pharmacy Act
1940 Drug and Cosmetic Act
1930 Dangerous Drug Act
1857 Opium Act
1954 Drug and Magic Remedies Act
1971 Medical Termination of Pregnancy Act (MTP)
1989 First ICH Indian pharmacopoeias:
1955 1st Edition IP
1966 2nd Edition IP

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1985 3rd Edition IP

1996 4th Edition IP
2007 5th Edition IP
2010 6th Edition IP
2014 7th Edition IP

TECHNIQUE FOR NANOPARTICLE PREPARATION:

 Desolvation, denaturation
 Emulsion & interfecial polymerization
 Emulsification diiffusion
 Salting out.
STRENGTHS
 HCl (IP)-36
 H2SO4-12 N
IMP CHARACTERS:
 Nutmeg-Aril
 Stropanthus- Arista (Awn)
 Cardamon- Arilode
 Colchicum- Strophiole
 Castor- Caruncle
WHITEFIELD OINTMENT
 6%benzoic acid
 3%salicylic acid.
 Used as keratolytic.
SMART POLYMER:
 Polylactic acid
 Polyglycolic acid
 Poly-lactide co-glycolide
 Poly (dl-lactide-co-caprolactone)
 N-isopropylacrylamide
Difference between Aldol condensation & Cannizaro reaction:
 If aldehyde & ketone have alpha proton than Aldol condensation occur.
 If not, than cannizaro reaction occurs.

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 SOME IMPORTANT NOTES FOR GPAT EXAM

 Betonite - derivative of monmorillonite.
 Hydrocaprolic acid-cyclic unsat fatty acid.
 Glucose-No UV abs.
 Vitamin B6 deficiency- sideroblastic anemia
 Smell of acetophenone when lobelia leaves burn.
 Rauwolfia tetraphylla devoid of recinnamine.
 Bromhexin- semisynthetic from vasaka.
 All electron withdrawing functional group are generally Meta directing except halogen group
 Stability order of carbocation is 3>2>1...
 Herceptin is Antineoplastic agent which cause CHF.
 Rasagaline is free from amphetamine prop due 2 aminoindane metabolite
 Rheumatoid factor is usually Ig M.
 Ca. sandoz is product of NOVARTIS.
 Phosphate is salt of Codeine.
 Seed of Indrajav is kurchi
 Transferosome are liposome used to increase Transdermal Permeation, in this
deformability achieved by using surfactant in proper ratio.
 Abacavir, a nucleoside reverse transcriptse inhibitor NRTI is converted to which
active metabolite?? Ans is Carbovir triphosphate.
 Cholesterol used in liposomes because it fills gaps created by imperfect packing of
lipids when protein are embeded in membrane.
 Clenbutrol - anabolic drug uesd illicitly by athletes 2 improve performance
 For chest infection in asthma-clarithromycin used.
 Lotaustralin- isoleucin
 Squill, Manna, Psyllium Contain Trisaccharide.
 Diluents can be used in ratio 5-10% in tablet.
 In MRI max of 1.5 tesla magnetic field strength can be used.
 Lutrol is known as intelligent polymer.
 Chemical shift-independent of magnetic field
 Secondary structure of protein-alfa-beta helix
 1960-prevention of cruelty to animals act.
 1963-CPCSEA came into existence.
 1998-breeding of and experimentation on animals act.

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 Hydrolysis of ethyl acetate is pseudo first order reaction

 Suspensions follow pseudo zero order reaction
 Cis form gives 5-12 delta value and trans form gives 12-18 delta value in NMR
 Polystyrene and water are both used as standard for calibration of IR
 B-cyclodextrin has max Solubility
 H-bond can detected by IR & NMR
 Free radicals are identified by E.S.R (electron spin resonance)
 TRIPS-trade related aspects of intellectual property rights
 TRIMS-trade related investment measures
 WIPO-world intellectual property organisation.
 Seliwanoffs reagent contain resorcinol + glacial acetic acid.
 Lucas reagent HCl+ZnCl2.
 Ames test to detect carcinogenicity
 Nitrocellulose is used as base in nail lacquers.
 Nucleosome contain DNA with histone protein in ratio 30:1
 Neumanns test is used for the identification of Casein.
 Gaultheria con. Methyl salicylate.
 PULSED FLOW IS THE disadvantage of reciprocating pump in HPLC.
 P.bracteatum do not contain morphine.
 BENTING & BEST founded insulin.
 H1N1-'N' stands for Neuramidase.
 Fiehls test is used for determination of sucrose
 Shinoda test for identification of flavanoids.
 Murexide test for caffeine.
 Bacteria need 0.5%NaCl for maintaining isotonicity not 0.9% NaCl.
 RITONAVIR IS also known as pharmacokinetic enhancer. Because it increases
bioavailability of antiviral drugs.
 Banana bond is the characteristic of cyclopropane.
 Caffine is Pseudo tannin.
 Rivastigmine is used in Alzheimer’s disease and it is a pseudo irreversible inhibitor of
cholinesterase enzyme.
 Carvedilol-a mixed adrenoceptor antagonist has antioxidant effect also.
 Minoxidil-K channel opener + release NO.
 Liquid Nitrogen temperature is -197 degree Celcius.

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 Caco2, a cell line model is used to classify drug for its BCS
 Classification bleomycin & nitrosourea coming under cycle nonspecific anticancer Agent
 All xanthophylline act on Adenosine receptor except enrophylline.
 Omalizumab used in asthma, it is anti IgE antibody.

BIOCHEMISTRY IMPORTANT PINPOINTS

 A living cell is true representative of life with its own organization & specialized Functions.
 Accumulation of lipofuscin, a pigment rich in lipids and proteins, in the cell has been
Implicated in ageing process.
 Leakage of lysosomal enzymes into the cell degrades several functional
macromolecules and this may lead to certain disorders (e.g. arthritis).
 Zellweger syndrome is rare disease characterized by the absence of functional peroxisome.
 Lysosomes are the digestive bodies of the cell, actively involved in the degradation of
Cellular compounds. Peroxisomes contain the enzyme cataloes that protects the cell
from the toxic effects of H2O2.
 The cellular ground matrix is referred to as cytosol which, in fact, is composed of a
network of protein filaments, the cytoskeleton.

 Mutarotation: The  and  Anomers of glucose have different optical rotations.

The specific optical rotation of a freshly prepared glucose ( anomer) solution in
water is +112.2o which gradually changes and attains an equilibrium with a constant
value of +52.7 o. ln the presence of alkali, the decrease in optical rotation is rapid. The
optical rotation of p-glucose is +18.7o (19 o)
 Mutarotation of fructose: Fructose also exhibits Mutarotation. Ln case of fructose,
the pyranose ring (six-membered) is converted to furanose (five-membered) ring, till
an equilibrium is attained. And fructose has a specific optical rotation of -92o at
equilibrium
 von Gierke's disease (type ii): The incidence of type I glycogen storage disease
is 1 per 200,000 persons. It is transmitted by autosomal recessive trait. This disorder
results in various biochemical manifestation
 Anderson's disease (amylopectinosis): A rare disease, glycogen with only few
branches accumulate; cinhosis of liver, impairment in liver function.

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 Pompe's disease: Glycogen accumulates in lysosomes in almost all the tissues; heart
is mostly involved; enlarged liver and heart, nervous system is also affected; death
occurs at an early age due to heart failure.
 Cori's disease: Branched chain glycogen accumulates; liver enlarged; clinical
manifestations are similar but milder compared to von Gierke's disease.
Distinct deficiency conditions of certain b-complex vitamins are known

VITAMIN DEFICIENCY

Thiamine Beriberi

Niacin Pellagra

Riboflavin Cheilosis, glossitis

Pyridoxine Peripheral neuropathy

Folic acid Macrocytic anemia

Cobalomin Pernicious anemia

 B-complex vitamin deficiencies are usually multiple rather than individual with
overlapping symptoms.
 A combined therapy of vitamin B12 and folic acid is commonly employed to treat the
patients of megaloblostic anaemias.
 Megodoses of niacin are useful in the treatment of hyperlipidemia.
 Long term use of isoniazid for the treatment of tuberculosis causes 86 deficiency.
 Folic acid supplementation reduces elevated plasma homocysteine level which is
Associated with atherosclerosis and thrombosis.
 Sulfonamides serve as antibacterial drugs by inhibiting the incorporation of PABA to
produce folic acid.
 Aminopterin and amethopterin, the structural analogues of folic acid, are employed in
the treatment of cancers.
 Lipoic acid is therapeutically useful as an antioxidant to present stroke, myocardial
infarction, etc.

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Colour reactions of proteins/amino acids Reaction Specific group or amino acid

REACTION SPECIFIC GROUP OR AMINO ACID

Biuret reaction Two peptide linkages

Ninhydrin reaction -Amino acids

Xanthoproteic Reaction Benzene ring of aromatic amino acids (Phe, Tyr, Trp)

Millons reaction Phenolic group(Tyr)

Hopkins-Cole Reaction lndole ring (Trp)

Sakaguchi reaction Guanidino group (Arg)

Nitroprusside reaction Sulfhydryl groups (Cys)

Sulfur test Sulfhydryl groups (Cys)

Pauly’s test Imidazole ring (His)

Folin coicalteau's test Phenolic groups (Tyr)

DRUGS OF CHOICE
1. Paracetamol poisoning- acetyl cysteine
2. Acute bronchial asthma: - salbutamol
3. Acute gout: - NSAIDS
4. Acute hyperkalemia: - calcium gluconate
5. Severe DIGITALIS toxicity: - DIGIBIND
6. Acute migraine: - sumatriptan
7. Cheese reaction: - phentolamine
8. Atropine poisoning: - physostigmine
9. Cyanide poisoning: - amyl nitrite
10. Benzodiazepine poisoning: - flumazenil
11. Cholera: - tetracycline
12. KALA-AZAR:- lipozomal amphotericin- B
13. Iron poisoning: - desferrioxamine ­
14. MRSA: - vancomycin
15. VRSA: - LINEZOLID

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16. Warfarin overdose: - vitamin-K (NIPER- 2009)

17. OCD: - fluoxetine
18. Alcohol poisoning: - fomepizole
19. Epilepsy in pregnency: - Phenobarbitone
20. Anaphylactic shock: - Adrenaline
21. MRSA Infection-Vancomycin
22. Malaria in Pregnancy-Chloroquine
23. Whooping Cough or Pertussis- Erythromycin
24. Kawasaki disease-IV Ig
25. Warfarin Overdose-Vit-K
26. Heparin Overdose-Protamine
27. Hairy Cell Leukemia-Cladirabine
28. Multiple Myeloma- Melphalan
29. CML-Imatinib
30. Wegner's granulomatosis-Cyclophosphamide
31. HOCM- Propranolol
32. Delirium Tremens-Diazepam
33. Drug Induced Parkinsonism-Benzhexol
34. Diacumarol Poisoning-Vit-K
35. Type-1 Lepra Reaction-Steroids
36. Type- 2 Lepra Reaction-Thalidomide
37. Allergic Contect Dermatitis-Steroids
38. PSVT- 1st-Adenosine, 2nd-Verapamil, 3rd-Digoxin
39. Z-E Syndrome- Proton Pump Inhibitor
40. Chancroid-Cotrimoxazole
41. Dermatitis Herpetiformis-Dapsone
42. Spastic Type of Cerebral Palsy-Diazepam
43. Herpis Simplex Keratitis-Trifluridine
44. Herpes Simplex Orolabialis-Pancyclovir
45. Neonatal Herpes Simplex-Acyclovir
46. Pneumocystis carinii Pneumonia- Cotrimoxazole for Nodulo
47. Cystic Acne- Retinoic acid
48. Trigeminal Neuralgia-Carbamezapine
49. Actinomycosis-Penicillin

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50. Plague- Streptomycin

51. Opioid Withdrawal- Methadone 2nd-Clonidine
52. Alcohol Withdrawal- Chlordiazepoxide 2nd-Diazepam
53. Post Herpetic Neuralgia- Fluphenazine
54. WEST Syndrome-ACTH
55. Diabetic Diarrhoea- Clonidine
56. Lithium Induced Neuropathy-Amiloride Communicable Disease:
57. Tetanus: PEN G Na; TETRACYCLINE; (DIAZEPAM
58. Diphteria: PEN G K; ERYTHROMYCIN
59. Pertusis: ERYTHROMYCIN; AMPICILLIN
60. Meningitis: MANNITOL (osmotic diuretic); DEXAMETHASONE (anti-inflammatory);
DILANTIN/PHENYTOIN (anti-convulsive); PYRETINOL/ENCEPHABOL (CNS stimulant)
61. Cholera: TETRACYCLINE
62. Amoebic Dysentery: METRONIDAZOLE
63. Shigellosis: CO-TRIMOXAZOLE
64. Typhoid: CHORAMPHENICOL
65. Rabies: LYSSAVAC, VERORAB
66. Immunoglobulins: ERIG or HRIg
67. Malaria: CHLOROQUINE
68. Schistosomiasis: PRAZIQUANTEL
69. Felariasis: DIETHYLCARBAMAZINE CITRATE
70. Scabies: EURAX/ CROTAMITON
71. Chicken pox: ACYCLOVIR/ZOVIRAX
72. Leptospirosis: PENICILLIN; TETRACYCLINE;
ERYTHROMYCIN
73. Leprosy: DAPSONE, RIFAMPICIN
74. Anthrax: PENICILLIN
75. Tuberculosis: R.I.P.E.S.
76. Pneumonia: COTRIMOXAZOLE; Procaine, Penicillin
77. Helminths: MEBENDAZOLE; PYRANTEL, PAMOATE
78. Meningitis: MANNITOL (dec. ICP); DEXAMETHASONE (relieve cerebral edema);
DIAZEPAM (anticonvulsant); PENICILLIN
79. Syphilis: PENICILLIN
80. Gonorrhoea: PENICILLIN

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Classification of antimicrobial agents: On the basis of their mechanism of action

Antimicrobial agents are used for the treatment of the microbial infections in the body and
the treatment is termed as chemotherapy. Paul Ehlrich is known as the father of
Chemotherapy who used Arsphenamine for the treatment of Syphilis. Chemotherapy is an
important perspective for the student’s GPAT preparation as lots of questions are asked from
this section. Here, we are introducing the classification of antimicrobial agents on the basis of
their mechanism of action.

Classification of antimicrobial agents

1. Antibiotics that inhibits Bacterial Cell Wall synthesis
 Pencillins,
 Cephalosporins
 Carbepenam
 Monobactam
Mechanism:
These drugs inhibit the transpeptidase enzyme used in the bacterial cell wall synthesis.

 Vancomycin
Mechanism:
This drug makes complex with C-terminal D-alanine residues of peptidoglycan precursors.
 Cycloserine
Mechanism:
It inhibits alanine racemase and D-alanyl-D-alanine synthetase.

2. Antibiotics that inhibit Ribosome function and prevent protein synthesis

a) Aminoglycosides: It causes misreading in mRNA
b) Tetracyclines: This class of drug binds with 30S ribosomes and inhibits the binding of
aminoacyl-tRNA into the A site of the bacterial ribosome.
c) Chloramphenicol: It binds with the peptidyl transferase enzyme on the 50S ribosome and
inhibits protein synthesis.
d) Spectinomycin
e) Azithromycin and Clarithromycin: Inhibits translocation which leads the protein
synthesis inhibition.

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3. Antibiotics that affect the function of cytoplasmic membranes

a) Antifungal drugs:
 Amphotericin B
 Ketoconazole
 Clotrimazole
 Fluconazole
 Miconazole
 Nystatin.
b) Bacitracin & Polymyxin B & E:
They cause the leaking of nuclear material which leads to the cell death.
c) Gramicidin: It produces aqueous pores in the cell membrane.

4. Antibiotics that inhibit Nucleic acid synthesis

a) Agents that interfere with Nucleotide synthesis:

 Zidovudine: DNA polymerase inhibition.
 Acyclovir: Thymidine kinase and DNA polymerase inhibition of Herpes virus.
 Flucytosine: Thymidylate synthetase inhibition.
b) Agents that interfere with DNA replication:
 Metronidazole: DNA strand breakage by the reduced Nitro group.
 Quinolones: DNA gyrase inhibition
c) Agents that inhibit RNA polymerase:
 Rifamycin
d) Agents that interfere with the precursor synthesis:
Sulfonamides: Inhibit the conversion of Pteridine & p-Amino Benzoic acid (PABA) into
dihydrofolic acid.
Trimethoprim: Inhibits the conversion dihydrofolic acid into tetrahydrofolic acid.
e) Agents that interfere with the Template function of DNA:

ALL THE BEST

DO THIS FIST MATERIAL WELL ALL IMP POINTS ARE INCLUDED
REVISE THEM DAILY: AMAR RAVAL

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PHARMACOLOGY GPAT NOTES PHARMAROCKS

Pharmacodynamics : - What drug does to body.

Pharmacokinetics : - What body does to the drug.

Pharmacotherapeutics : - Use of drugs in prevention & treatment of disease.

Clinical pharmacology : - Scientific study of drugs in man.

Toxicology : - Aspect of pharmacology deals with adverse effects of

Drugs.

Pharmacodynamic agents : - Designed to have pharmacodynamic effects in the

recipient.

Chemotherapeutic agents : - Designed to inhibit/kill parasites/malignant cells & does not

have or with minimal pharmacodynamic effects in recipient.

Orphan drugs : - Drugs or Biological Products for diagnosis/treatment/

Prevention of a rare disease.
E.g.:- Liothyronine (T3), Desmopressin, Baclofen, Digoxin Antibody.

Routes of drug Administration

1) Oral 2) Parentral

Injections:-
A) Intradermal: - given in to layers of skin. E.g.:- BCG vaccine, for testing drug
sensitivity.

B) S.C:- Only non-irritant drug are given absorption can be enhanced by enzyme
Hyalurinase S.C.drug implants can act as depot therapy. E.g.:- steroid hormones.
In children saline is injected in large quantities – Hypodermalysis.

C) I.M:- Mild irritants, suspensions & colloids can be injected by this route.

D) I.V:- Directly to vein.

E) Intra arterial: - Only used for diagnostic studies. E.g.:- Angiograms, embolism
therapy.

F) Intrathecal: - Spinal anaesthetics in to subarachinoid space.

G) Intra medullary: - Drug introduced to Bone marrow.

H) Intra articular & Intra tensional: - Drug administered into joints. E.g.:- Hydrocortisone
acetate in rheumatoid arthritis.

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PHARMACOKINETICS

Absorption of Drugs:-

A) Simple diffusion: - Bidirectional process rate of transfer across the membrane is

proportional to concn gradient. E.g.:- H20 soluble drugs with low mol-wt, lipid
soluble drugs.
B) Active transport: - requires energy – independent of physical properties of
membrane. E.g.:- H20 soluble drugs with high mol-wt.
Carrier mediated transport: - E.g.:- Intestinal absorption of Ca2+.
C) Pinocytosis: - Important in unicellular organisms like Amoeba.

Bioavailability: - Amount of drug reaches systemic circulation following a non-vascular

drug administration.
AUC Oral
F = AUC IV

Barriers:-
B.B.B:- made up of choroid cells (strong Barrier).
Testis Barrier: - made up of seroid cells.
Placental Barrier: - made up of sertoli cells (weak Barrier).
Endothelial Barrier: - in all blood cells (very weak).
For absorption of vitB12, IF factor is required which is synthesized by parietal cells?

Solubility of drugs:-
Ionized form – soluble
Unionized form – more absorbed

Distribution of drugs:-
Plasma protein binding: - many drugs have affinity towards plasma proteins, Acidic drugs
towards Albumin, Basic drugs towards acid Glycoprotein, Prothrombin, and Thromboplastin.
Radioligand binding: - is used to determine drug in protein complex.
1
PPB Vd
Tissue storage of drugs:-
Skeletal muscle, Heart: - Digoxin, emetine
Liver: - Chloroquine, tetracycline’s, digoxin
Kidney: - Chloroquine, digoxin, emetine
Thyroid: - Iodine
Brain: - CPZ, Acetazolamide, Isoniazid
Retina: - Chloroquine
Iris: - Ephedrine, Atropine
Bone & Teeth: - Heavymetals, Tetracycline’s
Adipose tissue: - Phenoxy Benzamine, Minocycline, ether, Thiopentane.

Metabolism of drugs :- ( Biotransformation / Detoxification)

Chemical alteration of drug in physiological system
1. Inactive form
2. Active metabolite, E.g.:- Codeine to morphine
3. Prodrug to active drug, E.g.:- L-Dopa to Dopamine

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Phase I metabolism: - Nonsynthetic

Reaction Enzyme Examples

Oxdn Monooxygenases cytp450 in lives Drugs with “OH” & “COOH”groups
Redn Reductases Halothane, trichloroethand
Hydrolysis Esterases Lidocaine procainide Benzocaine
Cyclisation Proguanil to cycloguanil
Decyclisation Phenobarbitone & Phenytoin

Phase II Metabolism: - Synthetic or Conjugation

Conjugation Endogenous substrate Examples

1. Glucouronide Glucouronic acid (glucose) “Oh” & “COOH” group drugs
2. Acetylation Acetyl co-A (Citric acid “NH2” & Hydrazine group drugs
cycle)
3. Methylation Methionine “NH2” & Phenol group drugs
4. Sulphate Sulfokinases Phenolic compds & Steroids
5. Glycine(rarely Glycine Salicylates & “COOH” group drugs
occur)
6. Glutathione Paracetamol
7. Ribonucleotide Purine & Pyrimidine
antimetabolites

Prodrug Active form Active drug Active Metabolite

Levodopa Dopamine Chloralhydrate Trichloroethanol
Enalpril Enalaprilat Phenacetin Paracetamol
L-Methyldopa L- Primidone Phenobarbitone
Methylnorepinephrine

Dipivefrine Epinephrine Digitoxin Digoxin

Benorylate Aspirin+Paracetamal Codeine Morphine
Proguanil Proguanil triazine Spironolactone Canrenone
Prednisone Prednisolone Amitryptiline Nor-tryptiline
Becampicillion Ampicillin Diazepam Desmethyl diazepam,
oxazepam

Sulphasalazine 5-amino salicylic acid Trimethadione Dimethadione

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Microsomal enzymes: - These are inducible by drugs, diet E.g.:- cytP450, Monooxygenases,
Glucouronyl transferase etc.
Catalyses many oxdn, redn, Hydrolysis & glucouronide conjugations.

Non Microsomal enzymes: - E.g.:- Flavoprotein oxidases, esterases, amidases & conjugases.
Catalyses some oxdn & redn, many hydrolytic reactions & all conjugations except
glucouronidation.

Hofmann elimination: - Inactivation of drug in body fluids by spontaneous molecular

rearrangement without enzymes. E.g.:- Atracurium.
Enzyme inducers: - Phenytoin, Barbiturates, Rifampicin, Carbamazepine.

Enzyme Inhibitors: - Cimetidine, erythromycin, chloramphenicol, ciprofloxacin, MAO

inhibitors, sulfonamides, verapamil, INH, Disulfiram etc.

Excretion of drugs: - elimination of drug in inactive form,

Urine – H20 soluble drugs, Feces – Unabsorbed drugs (complex drugs insoluble drugs),
Swets – salts & heavy metals,
Saliva – Hm, Lead, SCN, Lithium, & Tetracycline’s,
Lungs – gaseous drugs, Alcohol paraldehyde etc.,
Lacrimal – drugs applied to eye.

Rate of elimination
Clearance = plasma concn of drug

PHARMACODYNAMICS

Drug produces action by stimulation, depression, irritation, replacements cytotoxic action.

Mechanism of drug action:-

Properties Drugs
Physical Mass of drug Bulk laxatives, protectives
Adsorptive property charcoal, kaolin
Osmotic activity mgso4, mannitol
Radioactivity I131 & other isotope
Radio opacity Baso4, urografin
Chemical Neutralizing Antacids
germicidal Knmo4, I2
chelating EDTA, Penicillamine

Through enzymes: - Drugs may also increase or decrease rate of enzymatically mediated
reactions.
Stimulation: - e.g.:- Adrenaline stimulates Adenyl cyclase pyridoxine increases
decarboxylase activity.
a) Inhibition :-
1) Non specific inhibition: - Many drugs act by denaturing proteins. E.g.:- Hm, Acid &
Alkalies, Alcohol, Formaldehyde, Phenol etc.

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2) Specific inhibition :-
i) Competitive: - Physostigmine & neostigmine with Ach for sulfonamides with
PABA for folatesynthetase Allopurinol with Hypoxanthine for xanthine oxidase
carbidopa & methyldopa with L – Dopa for dopa decorboxylase.
ii) Non-competitive:- Ach & Papaverine on smooth muscles Ach & Decamethionine
on NmJ.
Through receptors:-

1) Clark-Arheneous theory (occupation theory):- The effect of drug is proportional to

fraction of receptors occupied by drug & maximum effect results when all receptors
are occupied.
2) Raton’s theory (Rate theory):- The effect of drug is a function of receptor occupation
& the rate of drug receptor combination. Here response depends on rate of
Association between drug molecule & receptor.
G proteins are Heterotrimeric proteins involved in receptor transduction it has 3 subunits.

PAx = - log (A) x,

PA2 = - log (A) 2,
PD2 = - log (a) 2,
Where (A) = molar concn of antagonist, where (a) = molar concn of against.

Eudismic ratio: - ratio of the activities of active enantiomer (eutomer) and inactive
enantiomer (distomer) in chiral pharmocodynamics.

AUTONOMIC NERVOUS SYSTEM

Sympathetic or Adrenergic system enables the individual to adjust to stress & prepares the
body for ‘Fight or Flight’ response.
Parasympathetic or Cholinergic mainly participate in tissue building reactions.
Both sympathetic & parasympathetic nervous system consists of myelinated preganglionic
fibre which forms a synapse with the cell body of non-myelinated post ganglionic fibre.

Synapse: - It is the structure formed by the close opposition of a neuron either with another
neuron or with effector cells.
The synapse b/w preganglionic & postganglionic fibres is termed as Ganglion
The synapse b/w postganglionic &receptors is termed as Neuroeffector junction.

Neurohumoral transmission: - The transmission of an impulse across the synapse in central

& peripheral nervous system occurs as a result of release of a neurohumoral transmitter
substance in to the synaptic cleft.

Junctional transmission: - The arrival of an action potential at the axonal terminals initiates
the series of events that put in to effect neurohumoral transmission of an excitatory/inhibitory
impulse across the synapse / neuroeffector junction.

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ADRENERGIC RECEPTORS:-

Receptor Agonist Antagonist Tissue Response Molecular

mechanism

a1 Methoxamine Quinazoline Blood vessel Vasoconstriction Stimulation of

derivatives Smooth muscle Contraction phospholipase-
( Prazosin) Liver Increased blood C & formation
glucose level of IP3 /DAG

a2 Clonidine Yohimbine. Islet cells Decreased insulin Inhibition of

Raulosine Platelets Aggregation Adenylcyclase
Vascular Contraction & neuronal
smooth muscles ca2+ channels

b1 Dobutamine Atenolol, Heart +ve Inotropic Activation of

Acebutolol, Juxta actions Adenylcyclase
Bisoprolol, glomerular cells Increased rennin
Metoprolol release

b2 Terbutaline, Butoxamine Smooth Relaxation Activation of

salbutamol Methyl muscles Adenylcyclase
Propranalol

b3 Sibutramine -------------- Adipose tissue Lipolysis Activation of

(Antiobesity) Adenylcyclase

Adrenergic receptors are membrane bound G- Protein coupled receptors which function
primarily by increasing/decreasing the intracellular production of secondary messengers’
cAMP/IP3- DAG. In some cases the activated G-Protein itself operates K+/Ca2+ channels or
increases prostaglandin production.

Classification of Adrenergic drugs:-

A. Therapeutic classification-
1. Pressor drugs: - Adrenaline, NA, Metarminol
2. Inotropic agents: - Dopamine, Dobutamine, Isoprenaline& Xamoterol
3. CNS Stimulants:-Amphetamine
4. Smooth muscle relaxants:-Adrenaline, Isoprenaline, Isoxsuprine& b2 stimulants
(Salbutamol)
5. Drugs used in allergy: - Adrenaline & ephedrine
6. Local vasoconstrictor effect:-Adrenaline, Naphozoline, Phenylephrine
7. Nasal decongestants: - Oxymetazoline, Tuaminoheptanesulfate
8. Anorectics: - Fenfluramine, dexfenfluramine&Phenteramine
9. Antiobesity: - Sibutramine

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B.Chemical classification:-
1. Catecholamines – Adrenaline, NA, Dopamine, 5-HT & Isoprenaline
2. Non-Catecholamines – Amphetamine, Ephedrine, Isoxsuprine, Mephentamine

Pharmacological Actions:-
1. Heart: - Due to its stimulant action on b1 receptors causes +ve inotropic actions. This is
associated with increased metabolism of myocardium & increased O2 consumption, thus
decreasing cardiac efficiency.

2. Blood vessels: - Raises systolic B.P. by its cardiac actions lowers diastolic B.P. by its
peripheral actions & hence not suitable in Hypotensive shock
 In moderate doses rise in B.P. is followed by a fall as it activates both the receptors.
This is called as ‘Biphasic response’.
 By prior administration of a blockers (ergot) leads to stimulation of only b2 receptors
& thus causes a fall in B.p. This phenomenon is called as ‘Dale’s vasomotor reversal’

Compared to Adrenaline, the NA has feeble actions on b2 receptors.

3. Smooth muscles: - relaxes bronchial muscles

Produce contraction of spleemic capsule producing a release of erythrocytes in to the
Peripheral circulation. This serves as protective mechanism during stress such as hypoxia &
Hemorrhage

4. Eye: - Mydriasis due to contraction of radial muscle fibres of IRIS. On topical application
do not produce Mydriasis but cause reduction in intraocular tension.
5. Respiration: - Bronchodilator & weak stimulant
6. Metabolic effects: - Increases Blood glucose, Blood lactate, free fatty acids. Inhibits
insulin release.
7. CNS: - Catecholamines cannot cross BBB

8. Miscellaneous: - Skeletal muscle contraction, Accelerates Blood coagulation, Platelet

aggregation, Leucocytosis& Eosonopenia. Inhibit cellular anaphylactic mechanism& prevent
release of allergic mediators (Histamine from mast cells)
Major excretory products are Vanillin mandelic acid

Therapeutic Uses:-
1. Na in elevating B.P. in shock
2. In glaucoma. To control hemorrhage
3. Cardiac resuscitation
4. Bronchial asthma
5. First line drug in Hypersensitivity
6. Along with Local anaesthetics to prolong their action.
Note: - Metyltyrosine/Metyrosine/2-methyl p-tyrosine inhibits Tyrosine hydroxylase in
synthesis of catecholamines & used in treatment of Pheocytochroma.

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Catecholamines Non-catecholamines
Not effective orally Orally effective
Do not cross BBB Crosses BBB
Susceptible to MAO Relatively resistant to MAO

Nasal decongestants: - Most of the Sympathetic amines on topical application produce Local
vasoconstriction & used as Decongestants
E.g. Oxymetazoline, Zylometazoline, Naphozoline.tuaminoheptanesulfate

Potency of agonists at a&b receptors are-

a- Adrenaline > NA > Isoprenaline
b- Isoprenaline > Adrenaline > NA

b2 selective receptor stimulants: -

 Isoprenaline used in Asthma will cause adverse cardiac effects due to action on b1
 Therefore selective b2 stimulants are used in Asthma & as Tocolytics
 E.g.Nylidrin.Isoxsuprine

Drugs used in CCF:-

 Dopamine& Dopexamine acts on a & b receptors as well as D1&D2 receptor.
 Dobutamine acts only on a &b receptor
 Xamoterol has selective b1 agonist action.

ADRENERGIC BLOCKING AGENTS:-

Classification:-
-Blockers:-

1. - Haloalkylamines- Dibenamine& Phenoxybenzamine

2. Imidazoline derivatives- Tolazoline& Phentolamine
3. Quinazolines- Prazosin, terazosin, tremazosin
4. Natural & dehydrogenated ergot alkaloids
5. Miscellaneous- yohimbine, Indoramine, Cpz

The receptor blockade produced by Dibenamine& Phenoxybenzamine is ir-reversible type.

Phenoxybenzamine is 6-10 times more potent than Dibenamine but has be converted to active
metabolite.

Therapeutics Uses: - In pheocytochroma, Hypertension, Secondary shock, CHF, BHP, Male

sexual dysfunction, Scorpion Bite.

-Blockers:-

1. Specific b- Blockers- Timolol, Nadolol

2. Blockers with membrane stabilizing action: - Propranalol, Oxyprenolol, Pindolol
3. Blockers with cardioselective action: - Atenolol, Acebutolol, Metoprolol&Esmolol
4. Both a &b blockers: - Labetolol, Carvedilol, Dilevilol&Medroxolol

Atenolol with poor lipid solubility does not cross BBB at all.

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 Propranolol, Alprenolol&Metoprolol are metabolized by liver, Practolol is largely

excreted unchanged by kidneys.
 Pindolol, Atenolol, Acebutolol& Timolol by both the routes.
 They are contraindicated in the myocardial insufficiency, Bradycardia, Asthma,
Heartblock& Insulin dependent diabetes.

T.Uses:-Anginapectoris, MI, Cardiac arrhythmia, Hypertension, Thyrotoxicosis,

Pheocytochroma, to decrease cardiac symptoms prior to important speech/meetings.
Propranalol is useful in prevention of Migrane & treatment of Essential tumor.

CHOLINERGIC DRUGS

Ach produces its dual actions as Muscarinic actions on Muscarinic & Nicotinic actions on
nicotinic receptors.
Muscarinic receptors (mol, wt-80,000) belong to g-Protein coupled receptors. Nicotinic
receptors are Pentameric proteins.

Receptors Agonist Antagonist Tissue Response Molecular

Mechanism
Nm Phenyl D-Tc NMJ End plate Opening of
trimethyl a- Bangarotoxin depolarization cation channels
ammonia
Nn Dimethyl Trimethophan Autonomic Depolarization& Opening of
phenyl Hexamethonium Ganglia firing of Post cation channels
piperazinum Succinylcholine ganglionic neurons.
Adrenal Secretion of
medulla catecholamines
M1 Oxytremonium Pirenzepine Autonomic Depolarisation & Stimulation of
Telenzepine Ganglia Late EPSP. phospholipase-
Atropine Gastric Histamine release C & formation
Glands of IP3 /DAG
M2 Methacholine Methocrotamine Heart Negative Inotropic Inhibition of
Atropine effect Adenylcyclase
M3 Bethnecol Atropine Smooth Contraction Stimulation of
Hexahydrosilede Muscles phospholipase-
nifol Secretory Increased secretion C & formation
Glands of IP3 /DAG

CLASSIFICATION:-
1. Esters of Choline – Ach, Methacholine, Carbachol& Bethnechol
2. Cholinomimetic Alkaloids – Pilocarpine, Muscarine&Arecholine
3. Cholinesterase inhibitors –

a) Reversible: - Physostigmine (Natural), Neostigmine.Pyridostigmine, demecarium Tacrine

(Acridine) used in Alzhmeir’s disease.

b) Ir-reversible: - Di-isopropylflurophosphate (therapeutically useful), OMPP, Malathion,

Parathion, Nerve gases (Tabun, sarin& Soman) Propoxur (carbamates)

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Pharmacological actions:- Undergoes Hydrolysis in Neutral or Alkaline medium & hence

preserved in Acidic medium.
On oral administration gets destroyed by GIT & hence given by I.v.
There is no circulating Ach in the Blood.

Muscarinic actions –
1. CVS: - Negative Inotropic actions, Dilates Blood vessels, Coronary arteries&veins.
Increases tone & rhythmic activity of smooth muscles of GIT & enhance Peristalsis.

2. Secretions: - Increases Nasal, Bronchial, Gastric, salivary, Pancreatic & Intestinal

secretions.

3. Eye: - on instillation no effect. But on injection to carotid arteries produces-

Constriction of Pupil (Miosis) – By contracting circular fibres of sphincter pupillae
Spasm of accommodation – Due to contraction of ciliary muscle, resulting in relaxation of
suspensory ligament of lens.

Nicotinic actions –
1. Increases output of Ach&NA from Post ganglionic sympathetic & Parasympathetic nerve
endings & increases B.p.

2. Produce paralysis of skeletal muscles at NMJ

Contraindications of choline esters: - Hyperthyroidism, Bronchial asthma, Peptic ulcer& MI

T.Uses: - Glaucoma, Post operative paralytic ileus & abdominal distension

Anticholinesterases: - they act by inhibiting true & Pseudo cholinesterases, thus causing
accumulation of Ach at various sites.

MOA: - Ach is inactivated by combination of 2 sites on enzyme Cholinesterase.

Anionic site bearing –ve charge attracts Quaternary nitrogen atom of Ach
Esteratic site which attracts carboxylic acid group of Ach. As a result of union of Ach with
cholinesterase the esteratic site of enzyme is acetylated & this results in splitting of choline.
The acetyl group in combination with esteratic site is However immediately removed as a
result of combination with water forming Acetic acid.
This sets esteratic site of enzyme free for further inactivation of Ach.

Reversible Anticholinesterases: - These are structurally similar to Ach & combine with
Anionic & esteratic sites of cholinesterase as well as with Ach receptor. However the
complex with esteratic site is much readily hydrolysed compared to Ach. This produces
temporary inhibition of the enzyme.
Uses – Glaucoma, Myasthenia gravis, Snake venomPoisonimg, Curare Poisoning&
Alzhmeir’s disease.

Ir-reversible: - These organophosphorous compounds combine only with esteratic site of

cholinesterase & consequently esteratic site is phosphorylated. The hydrolysis of esteratic site
is extremely slow /does not occur at all.
This will lead to Morbidity & Mortality, to overcome this we use cholinesterase reactivators
like Pralidoxime, Diacetylmonoxime&Obidoxime chloride.

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Note: - Edrophonium forms reversible complex only with Anionic site & Hence shorter
duration of action.
Echothiopate forms complex with both Anionic & esteratic sites & hence is much more
potent than other compounds.

ANTI-CHOLINERGIC DRUGS

They Block only Muscarinic actions but not the Ganglionic & skeletal neuromuscular actions
of Ach.

Classification:-
1. Natural alkaloids – Atropine, Scopalamine
2. Semisynthetic derivatives – Homatropine, Ipatropium
3. Synthetic compounds – a) Mydriatics: - Cyclopentolate, Tropicamide
B) Antisecretory: - Propantheine, Pirenzepine

MOA: - Belladonna alkaloids block muscarinic effects of Ach. The antagonism is of

competitive type which is reversed by an increase in Ach concentration at the cholinergic
nerve endings

P.actions:- Atropine & scopolamine have qualitatively similar actions except that Atropine is
CNS stimulant While Scopalamine is CNS Depressant.
1. Secretions – Decreases gastric secretions including total acidity & enzymes, leading to
decreased motility
Decreases Nasal, Bronchial & other secretions

2. Smooth muscles – Relaxation,

Causes Urinary retention

3. Eye - Mydriatic (1%), ciliary smooth muscle is paralyzed& produces tightening of

suspensory ligament resulting in flattening of lens with consequent increase in focal length.
Thus individual is able to see only at long distance (paralysis of accommodation/cycloplegia)
Because of sphincter paralysis he cannot constrict the pupils for viewing near objects clearly
in response to Bright light (Photophobia).

4. CNS – Atropine due to stimulation of medullary vagal nuclei & higher cerebral centers
produces bradycardia, increase rate & depth of respiration produced by Anticholinesterases.
Scopolamine by S.C.depresses RAS & Produces euphoria, Amnesia & dreamless sleep.

Therapeutic uses:-
 To control hypermotility, Colicky pain
 Organophosphorous compound poisoning
 As Antisecretory in Pre anaesthetic medication, Peptic ulcer& pulmonary embolism
 Motion sickness (scopolamine)
 Parkinsonism
 As Mydriatic& cycloplegic
 As Antispasmodic in drug induced diarrhoea, Spastic constipation,
Gastritis&Dysmenorrhoea.

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Contraindications:-
 May cause Congestive glaucoma in patients over 40yrs
 CCF with tachycardia
 Pyloric obstruction, pylorospasm&Cardiospasm

Ganglionic Stimulants: -
1. Nicotine, lobeline
2. Synthetic compounds (TMA, DMPP)
Activation of Nicotinic receptors facilitate the release of Ach, NA, dopamine, 5-HT & b Endorphin
 Nicotine releases GH, Prolactin & ACTH
 Increases muscle twitching followed by paralysis of myoneuronal transmission
 Induces Hepatic microsomal enzymes
 Increases BMR, reduces body weight & Appetite
 Causes lipolysis & releases free fatty acids Excessive release of cortisol affect mood
& contribute to Osteoporosis
 Vomitting due to action on CTZ, releases ADH by stimulating Supraoptic nuclei of
Hypothalamus
 Acidic urine Increases excretion of free nicotine, TMA & DMPP are excreted unchanged
 A.R:- Bronchitis, Emphysema, Tobacco Amlobia
Cigarette contains – Nicotine, Pyridine.CO, Furfural, Volatile acids& polycyclic hydrocarbons
Antidepressant like Bupropion is used to quit smoking in some individuals.

Note: - Mydriatics – Homatropine, Eucatropine & cyclopentolate

Other Antimuscarinics – Atropine methanitrate, Methoscopalmine bromide/Nitrates
Propantheline (probanthine) – used in peptic ulcer
Methantheline (Banthine), Dicyclomine
Pirenzepine (Gastrozepin) – in duodenal ulcer
Flavoxate (Uripas) & Oxybutynine (Ditropan) – In Dysurea,
In urinary frequencies Tolteridine – M3 antagonist in Urinary incontinence.

Ganglionic Blocking agents: - Blocks transmission across Autonomic ganglia (Both

sympathetic & Parasympathetic)
E.g.Hexamethonium, trimethomine&Hexamylamine

Skeletal muscle relaxants: - Used to treat spasm/spasicity

 Spasm – Involuntary contraction of muscle or group of muscles usually accompanied
by pain & limited function.
 Spasticity – due to increased skeletal muscle tone associated with decrease in skeletal
muscle power due to damage to the corticonotoneuronic pathways as in CNS injury,
cerebral palsy, stroke or Multiple sclerosis.

Classification:-
1. Drugs acting centrally – diazepam, Baclofen& Mephenesin
2. Drugs acting peripherally at NMJ –
a) Competitive Blockers: - D-TC,
b) Depolarization blockers: - Succinyl choline
c) Inhibitors of release of Ach from the motor nerve terminals: - Botulinum
Toxin – A & Antibiotics (Tetracycline& Aminoglycosides)
3. Drugs directly acting on Skeletal muscles: - Dantrolene

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PHYSIOLOGY OF SKELETAL MUSCLE CONTRACTION:-

1. Due to nerve action potential releases Ach from synaptic vesicles of motor nerve in to
synaptic cleft in large quantities, While in absence of NAP Ach is released due to miniature
end plate potential ( MEPP ) in small quantities.

2. The released Ach binds to nicotinic receptors on the motor endplate resulting in Localised
depolarization & development of End plate polarization (EPP). Depolarization is due to
influx of Na+ & Efflux of K+ ions from motor endplate.

3. When EPP is achieved the surround area of muscle fibre gets excited resulting in
development of muscle action potential (MAP) which initiates contraction of a muscle as a
result of release of ca2+ in to the Sarcoplasm.

4. Ach is metabolized enabling repolarisation of motor endplate& muscle fibre membrane.

This is achieved by reversal of ionic fluxes. The polarized muscle is now capable of
responding to fresh nerve impulse.

Skeletal muscle contraction can be blocked as follows –

1. Blocking transmission of impulse across the motor nerve – local anaesthetics

2. Inhibit the synthesis of Ach in motor nerve – Hemicholinum
3. Inhibit the release of Ach – Botulinum Toxin-A & antibiotics (tetracyclines& Aminoglycosides)
4. Modifying the motor endplate so that it does not respond to Ach – dantrolene

D-Tc: - dextrorotatory, quaternary ammonium alkaloid from Chondrodendron Tomentosum

Relaxes smooth muscles, Releases Histamine
On repeated Administration produces cumulative toxicity. Do not cross BBB & Placental Barrier.
Di-Methyl Tubocurarine has slightly longer duration of action

Other drugs: - Alcuranium Chloride- Similar to D-Tc

Pancuranium & Atracuranium – 5 times more potent than D-Tc
Vercuranium Similar to Pancuranium but duration of action is less.
Gallamine – Similar to D-TC, less potent completely excreted by Kidneys in Unchanged form.

DRUGS USED IN PARKINSONISM

Extra pyramidal motor disorder characterized by Rigidity, tremor & Akinesia.

Here Dopamine level decreases (responsible for Akinesia) & Ach level increases (Rigidity, Tremor).

Pathology: - There is a degeneration of neurons in substantial nigra & Nigrostatial

(Dopaminergic) Tract. The cause for this degeneration is due to the formation of free radical
(Metabolism of Dopamine by MAO-B). In normal Protective mechanisms Free radical are
quenched by glutathione & other protective mechanisms. If this fails the free radical will
cause DNA damage.
A synthetic toxin n-methyl 4-phenyl tetrahydropyridine is responsible for damage to
Nigrostatial tract.

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CLASSIFICATION:-
A. Drugs acting on dopaminergic system:-

1. Precursors of dopamine – L-Dopa

2. Drugs inhibit Dopamine Metabolism – A) Mao inhibitors: - Selelegine
B) Comt inhibitors:-Tolcapone& Entacapone
3. Drugs that release dopamine – Amantidine
4. Dopamine agonists – Bromocryptine, Lysuride, ropinrole, Pergolide, Pirebedil

B. Anticholinergics: - Trihexyphenidyl, Benzohexol, Benzatropine

C. Antihistaminics: - Promethazine

L-Dopa:-
 Pharmacologically inert, while its metabolite is active.
 Only 1% enters CNS, Most of the drugs get decarboxylated in GIT& liver
 It is excreted in urine partly unchanged& partly as Homovanilic acid.
 Gives Positive Comb’s test even though hemolytic anemia is not reported.
 Blood urea nitrogen & SGOT show a transient rise.

Contraindications:-
 Pyridoxine accelerates Peripheral decarboxylation of L-DOPA.
 Reserpine & Phenothiazines block the effects of dopamine to which L-Dopa is converted.
 Methyldopa intensifies the adverse effects of L-Dopa.
 Anticholinergics increase the stay of L-dopa in stomach & increase its degradation &
hence if needed must be taken 2hrs before taking L-Dopa.

Dopa decarboxylase inhibitors (DCI):-

 Pharmacologically inactive but on combined administration with L-Dopa they do not
enter BBB But decreases peripheral decarboxylation Of L-Dopa
E.g. Carbidopa, Benserazide

L-dopa – Carbidopa combination results in control of symptoms smoother, dose of L-

dopa Can be reduced up to 75%, Pyridoxine does not antagonize the actions of L- Dopa.

Selelegine (Deprenyl):- Inhibits MAO-B (responsible for dopamine metabolism)

L-dopa – Carbidopa – Selelegine combination must be avoided.
Note – MAO-A is responsible for Oxidative deamination of NA & 5-HT.

Amantidine: - Liberate dopamine from residual intact nerve endings & produces rapid
response than L-Dopa.

Dopamine Agonists: - Crosses BBB & need not to be converted to active metabolite.
Causes nausea& severe neuropsychatric adverse effects.

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CENTRAL NERVOUS SYSTEM

Drugs act on CNS in following ways:-

1. They may act directly on neurons & modify neuronal functions.
2. They may act reflexly by sending afferent impulses to the CNS via chemoreceptors,
Baroreceptors & peripheral nerves.
3. They may affect the nutrition & oxygen supply of the CNS by altering its Blood
supply or affecting its metabolism.

Neurotransmitters: - Which stimulate/Inhibit the post synaptic neurons after a brief latency
& have short duration of action.
Amines – Ach, NA, 5-HT, Histamine& Dopamine
Aminoacids – l-Glutamic acid, Aspartic acid, GABA &Glycine
Peptides – Substance-P, Cholecytokinin

Note: - Glutamate & Aspartate are excitatory amino acids. While GABA is inhibitory aminoacid.

Neuromodulators: - which act on the post synaptic neurons with a longer latency, have a
longer duration of action & modify the responsiveness of the target neurons to the action of
the neurotransmitters.

Aliphatic Alcohols:-
 Ethanol in 70% acts as antiseptic, in 40-50% as rubifacient & mild irritant action
 By dissolving in the lipid membrane of the neurons & altering the functions of ion
channels & other proteins. It increases GABA-mediated synaptic inhibition. It also
inhibits NMDA glutamate receptors. & depress CNS in descending order.
 Impairs Gluconeogenesis, Reduces synthesis of Albumin & Transferrin, Increases synthesis
of VLDL with consequent Hypertriglyceredemia&Diminishes fatty acid oxidation.
 Alcohol causes liver damage & cause Cirrhosis. Elevated Gamma glutamyl
transpeptidase (GGTP) is the most sensitive indication of Alcohol liver disease.
 Uses: - Appetizer, in methanol poisoning.

Treatment of Acute alcohol poisoning: - I.v glucose 50%,

I.v. Thiamine 100mg (Bolus), I.v. MgSo4 2-4gm

Treatment of Chronic alcoholism: - Disulfiram (Antabuse) & Citrated calcium cyanamide

(Carbimide)

Disulfiram – It interferes with the oxidation of acetaldehyde formed during the metabolism
of alcohol. It also inhibits dopamine-b Oxidase & thus interferes with the synthesis of NA.
This causes depletion of catecholamines.
4-Methyl pyrazole (inhibitor of alcohol dehydrogenase) used in treatment of methanol &
ethylene glycol poisoning.

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GENERAL ANAESTHETICS

They bring about loss of all Modalities of sensation in particularly pain along with a
reversible loss of consciousness.
Minimum Alveolar concentration: - It is the minimum amount of the anaesthetic in
pulmonary alveoli required to produce immobility in response to a painful stimuli, used in
dose fixation& Capacity of anaesthetic is measured.

Classification:-
A.Inhalational Anaesthetics –
1. Volatile liquids:-Chloroform, Diethyl ether, Trichloroethylene, Halothane, Enflurane
& Isoflurane
2. Gases: - Cyclopropane, Nitrous oxide, chloroform & Cyclopropane

B. Non – volatile (I.v.) Anaesthetics –

1. Inducing agents: - Thiopentone sodium, Propafol, Etomidate
2. Slower acting drugs: - a) Benzodiazepines – Diazepam, Lorazepam&Midazolam
b) Dissociative Anaesthetics: - Ketamine
c) Neurolept Analgesia: - Fentanyl + Droperdiol
(Analgesic) (Butyrophenone)

M.O.A.:- Most of the general anaesthetics acts by blocking synaptic transmission but some
act by blocking excitatory transmission but some act by prolonging the synaptic inhibition (
Potentiaion of GABA-A ) thus depressing all the functional elements of CNS.
Inhalational anaesthetics, Barbiturates & Benzodiazepines act by potentiating the action of
the inhibitory neurotransmitter GABA at GABAA receptor.
Ketamine selectively inhibits the excitatory NMDA type of glutamate receptor.

Stages of Analgesia:-
1. Stage of analgesia – Minor surgical procedures such as incision of Abcess, dental
extraction
Are carried successfully in this stage.
2. Stage of delirium – must be avoided.
3. Stage of surgical anaesthesia – Includes 4 Planes.
4. Stage of respiratory Paralysis –

Pre-Anaesthetic medication: - Term applied to the use of drugs prior to the administration
of an anaesthetic agent, with the objective of making anaesthesia safer & more agreeable to
the patient.
1. Opoid analgesics – Morphine, Pethidine, Buprenorphine to reduce anxiety &
apprehension of the patient.
2. Sedative & Tranquilizers – Benzodiazepines& Barbiturates
3. Anticholinergics – Atropine or Scopalamine
4. Antiemetics – Phenothiazines(Promethazine & trimeprazine), Metoclopramide
5. H2 Blockers – Ranitidine & famotidine to avoid gastric regurgitation & aspiration
pneumonia
6. Neuroleptics – Cpz, triflupromazine

Alphaxolone is a steroidal drug having anaesthetic property.

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SEDATIVE & HYPNOTICS

Sedative reduces excitement & is commonly used as an Anxiolytic

Hypnotic produces sleep resembling natural sleep.

CLASSIFICATION:-

1. Barbiturates – Long acting (Phenobarbitone & mephobarbitone)

Short acting (Butobarbitone, Secobarbitone, and Pentobarbitone)
Ultra short acting (Thiopentone, Methohexitone& Hexobarbitone)
2. Benzodiazepines – Anticonvulsant (Diazepam, Clonazepam& Clobazepam)
Antianxiety (Diazepam, oxazepam, lorazepam, alprazolam, Chlordiazepoxide)
Hypnotics (Diazepam, nitrazepam, flurazepam, temazepam, midazolam)
3. Alcohols – chloralhydrate, Ethchlorvynol
4. Aldehydes – Paraldehyde
5. Acetylated carbinols – Ethinamate, Meprobamate
6. Imidazopyridine – zolpidem
7. Cyclopyralone – Zopiclone
8. Oxazolidine Diones – Paramethadione & Trimethadione
9. Miscellaneous – Methaqualone, antihistaminics & scopolamine

M.O.A.:-

Barbiturates – They act primarily at the GABA: BZD receptor – Cl- channel complex &
they potentiate GABAergic inhibition by inducing the opening of the chloride channel.

Benzodiazepines – They act by enhancing presynaptic/postsynaptic inhibition through a

specific BZD receptor, which is an integral part of the GABAA receptor – Cl- channel
complex. The binding site for GABA is located in the b subunit while the a subunit contains
the BZD binding site. The modulatory BZD receptor increases the frequency of cl- channel
opening.

DRUGS AFFECTING GABAA RECEPTOR- CL- CHANNEL COMPLEX ARE

GABAA GABAB BZD site(a site)

Endogenous agonist GABA GABA
Agonist Muscimol Baclofen BZD
Competitive Bicculine Saclofen Flumenazil
antagonist

Inverse agonist b carboline

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ANTI – CONVULSANTS
These are the agents used to treat convulsions
Agents that produce convulsions are Bicculine, Pentylene tetrazole, Strychnine& Picrotoxin
CLASSIFICATION:-
1. Hydantoin derivatives – Phenytoin,Methatoin & ethatoin
2. Barbiturates – Phenobarbitone & Primidone
3. Iminostilbines – Carbamazepine
4. Succinimides – Ethosuximide & Methsuximide
5. GABA Transaminase inhibitors – Sodium Valproate, Vigabatrin
6. GABA reuptake inhibitors – Tiagabin
7. GABA Agonists – Gabapentin
8. Benzodiazepines – Diazepam,Clonazepam&Clobazepam
9. Miscellaneous– Lamotrigine,Acetazolamide,Sultiame(Sulphonamide), Amphetamine

1. Hydantoin derivatives:-
M.O.A. – It acts by inhibiting the spread of seizure discharges in the Brain & Shortens the
duration of after discharge. The drug causes dose-dependent block of sodium channels, thus
reducing the neuronal sodium concentration leading to a reduction in Post titanic potentiation
(PTP) & to increase the neuronal Potassium concentration.
AR – Hyperplasia, Hypertropy of gums, Osteomalacia, Hyperosmolar&non-Ketotic Coma.
Uses – Grandmal, Focal cortical epilepsy. Psychomotor seizures & Neuralgia

2. Barbiturates;-
M.O.A. – Potentiates GABAergic inhibition
AR – Vit-K depletion, Megaloblastic Anaemia & osteomalacia
USE: They are used in the treatment of resistant grandmal, cortical seizures.

Primidone is a Deoxy Barbiturate converted in the liver to 2 active metabolites

Phenobarbitone & Phenyl ethyl malonamide.

3. Iminostilbines: - It increases threshold to PTZ & Electroshock convulsions

AR – Peripheral neuritis, Agranulocytosis, Obstructive jaundice, Aplastic anaemia &
Thrombocytosis, Diplopia, Vertiga, Ataxia & Lupus like Syndrome.
Uses – Temporal lobe & Grandmal epilepsy, Trigeminal neuralgia, Diabetes insipidus &
Alternative to Lithium CO3 in Mania.

4. Succinimides: - It acts by suppressing T-Current

AR – Blood dyscrasiasis, SLE, Psychic disturbances & GIT disturbances.
Used in Temporal lobe epilepsy

5. GABA transaminase Inhibitors: - Potentiates Post synaptic GABA activity & decrease
brain levels of EAA.

6. Oxazolidine Diones: - Raises threshold to Seizures

AR – Hemeralopia, Kidney damage Used in Petitmal epilepsy

7. Miscellaneous:-
Lamotrigine – blocks voltage sensitive sodium channel
Acetazolamide – Inhibits CA & acts by increasing CO2 levels in the Brain or by decreasing
sodium there by increasing Seizure threshold.

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ANTIPSYCHOTICS

Antipsychotics/ Tranquilizers/ Ataractics are the drugs reduce Apomorphine induced

Sterotype & Amphetamine induced Hyperactivity & also inhibit conditional avoidance
response and cause some Ataxia.

CLASSIFICATION:-
1. Phenothiazine derivatives –

a) Aliphatic side chain: - CPZ, triflupromazine

b) Piperidine side chain: - Thioridazine & Mesoridazine
c) Piperazine side chain: - trifluperazine, Fluphenazine&thioproperazine

2. Butyrophenones – Haloperidol, Trifluperidol, Droperdiol&Penfluridol

3. Rauwolfia Alkaloids – Reserpine
4. Thioxanthines – Chlorprethixene, Thiothixene& Flupenthixol
5. Indole derivatives – Molindone
6. Substituted Benzamides – Sulpiride
7. Atypical neuroleptics – Clozapine (Dibenzodiazepines), Reserpidone
8. Miscellaneous – Oxypertine, Loxapine, Pimozide
M.O.A:-
Most of them act by following 3 ways-
1. Cause Blockade mainly of post synaptic Dopaminergic (D2) receptors & to a small extent
5-HT receptors.
2. Modify functions of Mesolimbic system.
3. Reduce incoming sensory stimuli by acting on the brain stem reticular formation.

All Antipsychotics except clozapine have potent Dopamine (D2) blocking action.
Dopamine acts as an excitatory neurotransmitter at D1 & D5 while Dopamine acts as an
inhibitory neurotransmitter at D2 , D3& D4 receptors.
Clozapine acts by 5-HT2 as well as a1 Blockade.
Reserpidone acts by 5-HT2 as well as D2 Blockade.

AR- Anticholinergic effect, Extrapyrimidal effects, Weight gain

ANTI-ANXIETY AGENTS

Elevated plus Maze test is used to evaluate Anti-anxiety agents.

Class Drugs M.O.A.

Benzodiazepines Diazepam,Alprozolam,Oxazepam, Potentiates GABAergic
Lorazepam,Chlordiazepoxide Inhibition.
Azapirone Buspirone,Gepirone,Ipsapirone Stimulates Presynaptic 5-HT1A
Autoreceptors.
Others Meprobamate,Hydroxyzine Antihistaminic with sedative,
antimuscarinic & Spasmolytic
actions.
b- blockers Propranolol By reducing B.p. tremor &
palpitation.

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AFFECTIVE DISORDERS

Refers to pathological change in mood state. The 2 Extremes are Mania & Depression.
Drugs like Antidepressants & Antimanics (Mood stabilizers) are used.

Anti-Depressants:-

A.MAO Inhibitors
1. Non-selective
a) Hydrazines: - Phenelzine, Isocarboxazid& iproniazid Irreversible
B) Non-Hydrazine:- Tranylcypromine

c) Reversible: - Moclobemide
2. Isoenzyme Selective
a) MAO-A Inhibitor: - Clorgiline, Moclobemide
b) MAO-B Inhibitor: - Selelegine (Deprenyl)

B. Tricyclic Antidepressants
1. Nor-Adrenaline & 5-HT reuptake Inhibitors
Imipramine, Amitryptiline, Trimipramine, Doxepin, Clomipramine, Dothiepin & Venlaflexin

2. Nor-Adrenaline reuptake Inhibitors

Nortryptyline, Desipramine, Protryptiline, Amoxapine

3. Selective 5-HT reuptake Inhibitors

Fluoxetine, Fluvoxamine, Paroxetine, sertraline & Alpacrolate

4. Atypical Antidepressants
Trazodone, Bupropion, Mianserin, Tianeptine

M.O.A:-
MAO Inhibitors act by inhibiting MAO (Enzyme responsible for degradation of Catecholamines).
Tricyclic Antidepressants Inhibit active uptake of Biogenic amines NA & 5-HT in to their
respective neurons & thus potentiate them.

ANTIMANICS/ MOOD STABILIZING DRUGS:-

Lithium carbonate – They act by replacing Na+ by Li+ this affects ionic fluxes across Brain
cells or modify the property of cellular membranes.

They decrease the release of NA & dopamine in the Brain with out affecting 5-HT release.
They inhibit action of ADH on distal tubules & causes diabetes insipidus like state.

Alternatives used as Antimanics – Carbamazepine, Sodium valproate.

Hallucinogens: - (Psychomimetics/ Psychedelics/ Psychodysleptics/ Psychotogens)

These drugs alter mood, behavior, thought & perception in a manner similar to that seen in
Psychosis.

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Classification:-
1. Indole amines: - LSD, Psilocybin, Harmine, Bufotenine & dimethyltyrptamine
2. Phenyl alkylamines: - Mescaline
3. ArylcycloHexylamines: - Phencyclidine
4. Cannabinoids: - Tetrahydro Cannabinol

Phencyclidine is a Hallucinogen structurally similar to Ketamine.

Psychomotor stimulants: -
Caffeine, Amphetamine & Piperidyl derivatives (Pipradrol & Methyl phenidate).
Used in Narcolepsy, Catoplexy & Attention deficit Hyperactivity disorder (ADHD).

OPIOID ANALGESICS

 The opioid drugs produce their effects by combining with opioid receptors which are
widely distributed in CNS & other tissues.
 Opiods & their Antagonists act at Mu receptors.
 The side effects such as vomiting, Sweating & Hallucinations are due to action of
drugs on subtype of Kappa receptors.

m j k
Endogenous Endomorphin 1&2 Leu/Meth Dynorphin A
agonists b-Endorphin (31a.a) Enkephalein (5a.a)
Exogenous agonists Morphine Morphine Ketocyclazocine
Selective agonists b-Funaltrexamine Norbinaltorphimine
m1-naloxanazine

B-Endorphin is a pain modulator in the CNS derived from Pro-opio-Melanocortin

Opium alkaloids are divided as

1. Phenanthrene group
2. Benzyl isoquinoline – Papaverine, Noscapine
Devoid of analgesic activity, Intracarvenosal injection of papaverine causes penile
errection. Noscapine is a potent releaser of Histamine. & large doses cause Hypotension.

Morphine – Used as sulfate/HCl salt

Produces Analgesia, Euphoria, sedation& Hypnosis.
Causes direct depressant action on Brain stem respiratory centre & reduce the sensitivity of
medullary respiratory centre to increased plasma CO2 concentration. With toxic doses
breathing is entirely maintained by ‘Hypoxic Drive’ mediated through the carotid & aortic
body chemoreceptors & results in ‘Cheyne Stokes Respiration’.
Causes Miosis, Nausea Cough suppression, Stimulates Vagus nuclei, Excites spinal cord &
raises CSF.It also releases ADH.
GIT: - spasms followed by increase in intrabiliary pressure.

T.uses – Powerful analgesic, sedative, Pre-anaesthetic medication, general anaesthetic

Contraindications- In, hypopitutarism, Addison’s disease, Head injuries, impaired kidney &
liver functions.

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Codeine – Devoid of respiratory depression, enhances analgesic effect in combination with Aspirin.
Note: - All the 3 types of receptors are antagonized by Opioid antagonists such as Naloxone
& Naltrexone.
The drugs which act as partial agonist-antagonists at the opioid receptors are Nalorphine,
Levallorphan, and Pentazocine&Nalbuphine.

NSAIDS: - Extensively protein bound drugs.

Classification –
1. Salicylates:-
2. p-Aminophenol derivatives: - Phenacetin, Paracetamol, & Acetanilide
3. Pyrazolone derivatives: - Phenyl Butazone
4. Indole & related drugs: - Indomethacin, Sulindac
5. Heterocyclic Aryl acetic acid derivatives: - Diclofenac, Tolmetin&Keterolac
6. Propionic acid derivatives: - Ibuprofen, fenoprofen, Naproxen, Ketoprofen
7. Fenamates: - Flufenamic acid, & Mefenamic acid
8. Oxicams: - piroxicam
9. Sulfonanilides: - Nimesulide

M.O.A:- Cox-1 is present in Stomach, Kidney& Blood vessels. Where as Cox-2 in

inflammatory cells& activated leucocytes.NSAIDS act by inhibiting COX, responsible for the
conversion of arachidonic acid to Prostaglandins.

Salicylates: - prevent the release of Histamine, Lowers ESR (erythrocyte sedimentation rate)
Inhibits platelet aggregation. In small doses elevate plasma urate levels while in large doses
causes uricosuria. Induces release of adrenaline from adrenal medulla.
In case of salicylate poisoning supplement of Vit-k is given along with other formalities.
Trusses – Antirheumatic,

Antiplatelet, Analgesic, Antipyretic, Counterirritant, Keratolytic, fungistatic, Antiseptic,

Antiinflammatory.
Selective Cox-2 inhibitors: - Nimesulide, celecoxib, rofecoxib, meloxicam

GASTROINTESTINAL DRUGS

Achlorhydria: - Absence in production of HCL leading to improper digestion. It can be

treated by 10ml of 10% HCL diluted 100ml H20.

Hypochlorhydria: - decreased production of HCL.

Sialorrhoea: - increased salivary production

ORS: - Oral rehydration solution. Glucose – 20g, Nacl – 3.5g, Kcl – 1.5g, NaHCo3 (2.5g) or
tri sodium citrate (2.9g) – distilled water (1-L).

Mumps: - infectious, inflammatory swelling of paratoid & other salivary glands.

Hydragogue: - Drug which produces watery stools.

Dyspepsia: - disorder of abdomen or chest with flatulence, nausea etc.

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Achyliagestrica: - Absence of HCL.

Bitters: - They increase appetite by promoting gastric acid secretion. E.g.:- gentian, chirata,
picrorrhiza Alcohol & 2 other Antihistaminics (cyproheptidine, Buclizine) also acts as
appetite stimulants.

Anorexia nervosa: - Chronic disease characterized by loss of appetite, weight loss,

physiological & psychological alterations.

Digestants: - which aid in digestion in GIT.

E.g.:- Diastase & Taka diastase – Amylolytic,
Papain – Proteolytic,
Pancreatin – Amylolytic & Proteolytic,
Bromelain – Amylolytic, lipolytic & proteolytic,
Lipase – Lipolytic.
Carminatives: - expels gas with relaxation of sphincters. E.g.:- Volatile oils & Spices.

Gall stone dissolving drugs: - Ursodiol & chenodiol

Bile salts are essential for digestion of cholesterol, when the amount of cholesterol in body
increases, they form gall stones, and thereby bile acids are used for dissolving gall stones.

Bile acids: - Chenodiol (cholic acid) & Ursodiol (taurocholic acid) both inhibit absorption
of cholesterol.

Bile salts: - Sodium glycocholate & sodium taurocholate.

Bile pigments: - Bilurubin, Biliverdin, Stercobilin & Stercobilinogen.

Peptic ulcer: - due to imbalance between aggressive factors (acid, pepsin & H-pylori) &
defensive factors (gastric mucus & bicarbonate secretions, PG’S innate resistance of the
mucosal cells).

METHODS OF TREATING PEPTIC ULCER:-

1. By reducing gastric acid secretion :-

Class Drugs M.O.A A.R.

H2 Blockers Cimetidine Blacks H2 receptors Cimetidine causes
ranitidine gynacomastia &
Roxatidine inhibiting cytp450
famotidine
Proton pump Omeprazole H+K+ inhibits Atpase Nausea headache loose
inhibitors Lansoprazole present in parietal cells stools
Pantoprazole
Anticholinergies pirenzepine Decreases cholinergic Intolerable side effects
Propantheline secretions
PG Analogues Misoprostol Inhibit acid secretion & Contraindicated in
Rioprostil Enprostil promote mucus & pregnancy
bicarbonate secretion
Inhibit gastrin production

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Cimetidine Produces Anti Androgen Effect by displacing the Dihydro testosterone from the
cytoplasmic receptors, Increases plasma prolactin level & inhibits the metabolism of Estrogens.

2. Neutralization of gastric acid: - Systemic antacids – NaHco3, Non Systemic antacids –

Al (oH)3, Mg (oH)2.

MAGALDRATE – Hydrated complex of Hydroxy Magnesium Aluminate.

Acid neutralizing capacity: - Number of milli equivalents of 1N HCL that is brought to PH

3.5 in 15 mins by unit dose of the preparation.

3. Ulcer protectives :-
Sucralfate – Aluminium salt of sulfated sucrose at pH – 4 it polymerizes to form a gel & gets
deposited on the wall of stomach.
Colloidal Bismuth Sub citrate – increases Pg synthesis. They also destroy H.Pylori

4. Ulcer healing drugs: - Carbenoxolone sodium, Deglycyrrhizinised licorice.

5. Anti.H.Pylori:- Metronidazole, Tinidazole.

Combination therapy = Clarithromycin + Amoxycillin + Omeprazole.

Polymethyl siloxane: - Collapes froth, improves dispersion of Antacid, reduces gastro

esophageal reflux & thus relieves Heart Burn.

Drug contraindicated in peptic ulcer: Caffeine, reserpine, Aminophylline, glucocorticoids, NSAIDS.

EMETICS

Emetine, Apomorphine, Hypertonic saline solution, mustard (sinigrin)

Anti emetics:-
Anticholinergies – Hyoscine, Dicyclomine
H1 Antihistaminics – Promethazine, Diphenhydramine, Cyclizine, Cinnarazine
Neuroleptics – CPZ, Haloperidol, Prochlorperazine
Prokinetic drugs – Metoclopramide, Domperidone,
5HT3 antagonists – Ondansetron, granisetron

DRUGS ACTING ON RESPIRATORY SYSTEM

Respiratory quotient: - ratio of oxygen consumed to the carbondioxide evolved.

1. Pharyngeal demulcents: - sooth the throat directly as well as by promoting salivation

E.g.:- Lozenges, Glycerine, Liquorice.
2. Expectorants (mucokinetics):-
Directly acting:- eucalyptus & lemon oil, Guainaphenesin, Vasaka.
3. Reflexly acting: - saline expectorants (NH4cl, KI, K-citrate)
4. Antitussives :-
 Opioids – Codeine, morphine.
 Non-Opioids – Noscapine, Dextrometrorphan, Clophedianol, Carbetopentane
& Oxeladin

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5. Antihistaminics – Chlorpheniramine, diphenhydramine,Promethazine

6. Mucolytic agents: - decreases viscosity of sputum. E.g.:- Acetylcysteine, bromohexine,
Ambroxol pancreatic dornase.
7. Nasal decongestants: - ephedrine, phenyl ephrine Naphazoline & Oxymetazoline.

Bronchodilators:-

1. Sympathominetics – ephedrine, adrenaline, salmeterol

2. Methyl xanthines – Theophylline
3. Anticholinergics – Ipratropium bromide Atropine methonitrate.

 Cromolyn sodium is a prophylactic agent that stabilizes most cells in asthma.

 Prednisolone is life saving in serve status asthamaticus & inhibitor of
phospholipase A2.
 Ipratropium is bronchodilator in chronic obstructive pulmonary disease with
least cardiac effects.
 Ketotifen – Orally active, Prophylactic agent in Bronchial Asthma & Allergic
disorders.
 Inhalational Steroids – Beclomethasone, dipropionate& Budesonide.

Catarrh: - state of irritation of mucous membranes associated with a copious secretion of mucus.

DRUGS ACTING ON C.V.S

Cardiac glycosides: - These glycosides have cardiac inotropic activity. They increase
myocardial contractility & output without proportionate increase in O2 consumption. E.g.:-
Digitoxin, Digoxin, Lanatoside – C, quabain

M.O.A:- Cardiac glycosides selectively bind to membrane bound Na+/K+ ATPase pump.
This results in accumulation of Na+ intracellularly and this indirectly results in intracellular
accumulation of Ca2+, this leads to increased myocardial contractility.
Therapeutic index = 1.5 – 3.0 (Digitalis)

Properties Digitoxin Digoxin Lanatoride – c Quabain

Oral absorption Excellent Good Low Low
PPB 95 % 25% 25% Poor
2plasma t1/2 7 days 2 days 2 days 1 day
Potency Less Intermediate Intermediate High
Elimination Hepatic Renal Renal Renal

Uses: - CCF, cardiac arrhytmias such as atrial flutter & atrial fibrillation.

Cardiac arrhythmias: - refers to changes in Cardiac rhythm.

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Antiarrhythmic drugs:-

I – Sodium channel Blockers

Class M.O.A Examples

IA Prolongs repolarisation Quinidine, Procainamide Disopyramide.
IB Shortens repolarisation Lidocaine, Phenytoin tocainide.
IC Slows conduction Encainide, Flecainide Propafenone.

Affinity towards Na+channel = class IC > class IA > class IB

II – B Blockers E.g.:- propranalol

M.O.A:- slows conduction & suppresses automaticity.

III – K+ channel blocker E.g.:- Amiadarone, Bretylium, Sotalol

M.O.A:- prolongs refraction

IV – ca2+ channel blocker E.g.:- verpamil, Diltiazem blocks inward ca2+ current.

V – Digitalis.

Cardiac arrhythmic disorders First line drugs/ Drug of choise

PSVT Adenosine/Verpamil
Av Block Atropine
Atrial extra systole Quinidine
Atrial flutter/Atrial fibrillation Verapamil
Ventricular extra systole/ventricular tachycardia Lidocaine
Wolf Parkinson white syndrome Amiodarone/Flecainide

ANTI-ANGINAL DRUGS

Used to treat Angina pectoris

Angina pectoris: - where the O2 demand of the myocardium exceeds that of the supply.

Stable angina: - generally caused due to stress

Unstable angina: - due to occlusion of coronary arteries by plague.

Variant / Prinzmetal angina: - It occurs at rest due to recurrent localized coronary

vasospasms.

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Classification:-

A. Organic nitrates: - i) short acting: - glyceryl trinitrate.

ii) Long acting: - ISDN, ISMN.
B. B – Blockers: - Propranalol.
C. Ca2+ channel Blockers: - Verapamil, Nifedepine, Diltiazem.
D. K+ channel openers: - Nicorandil, minoxidil.
E. Antiplatelet drugs: - Aspirin, Dipyridamole.
F. Cytoprotectives: - Trimetazidine.

Nitric oxide (EDRF) is synthesized in body from L-arginine as follows –

 L-arginine N.O.synthetase N.O. +citrulline

 Organic nitrates are rapidly denitrated in the smooth muscle cell to release the
reactive free radical N.O. that activates guanyl cyclase, which causes the formation of
CGMP from GTP. CGMP causes desphorphorylation of MLCK through CGMP
dependent proteinkinase. Reduced availability of phosphorylated MLCK interferes
with activation of myosin & it fails to interact with actin & this leads to relaxation.

 Nitrates are also used to treat cyanide poisoning as nitrates form methemoglobin with
Hb. So that cyanide cannot act on methemoglobin.

Potassium channel openers: - since intracellular concn of K+ is much higher compared to

extra cellular region, K+ channel opening results in outflow of K+ ions & hyperpolarisation.
Uses: - Angina pectoris, Hypertension, CHF.
AR: - Hirsutism.

Desferrioxamine: - A high affinity iron cheater used as a protective in ischemic myocardial

injury through its anti-free radical effect.

Vasodilators: - They are used in Hypertension, myocardial infarction, angina attacks etc.
1) Arteriolar vasodilators: - Hydralazine, minoxidil, nifedepine, diazoxide, nicorandil.
2) Venous vasodilators: - Glyceryl trinitrate, ISDN.
3) Mixed vasodilators: - Losartan, sodium nitroprusside, prazosin.

Selective phosphodiesterase inhibitor: - Amrinone is an inotropic agent. It is a bipyridine

derivative & inhibits PDE – III.
Milrinone (derivative of Amrinone) & 10 times more potent than Amrinone.
Drotavarin inhibits PDE – V.

Non-selective PD inhibitor: - Cilastazole & Theophylline dithiothreol is used to stop the

action of nitrates by removing nitrate groups attached to ‘SH’.

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ANTIHYPERTENSIVE DRUGS:
 These are drugs used to lower BP in Hypertension.
 Blood pressure is the product of cardiac output and peripheral resistance.
 Cardiac output is the amount of blood pumped by the heart in one minute and is
therefore the product of stroke volume and the heart rate. Stroke volume refers to the
volume of blood pumped during each contraction.
 B.P = C.O * T.P.R, C.O = stroke volume * Heart rate.
 Thus it can be observed that most of the antihypertensive drugs act by either
decreasing peripheral resistance or by decreasing cardiac output.

MECHANISM OF
CLASS DRUGS ADVERSE EFFECTS
ACTION MOA
Enalpril,
(prodrug)
They inhibit ACE
Lisinorpril,
essential for the
(prodrug)
conversion of AT-I to AT- Dry cough, angioedema,
Ramipril
ACE inhibitor II, Urticaria and taste
(prodrug)
disturbance.
Captopril
which is a potent
(nonprodrug)
vasoconstrictor
Saralasin

Losartan,
irbesatran
valsartan,
Angiotensin They antagonize the
telmisatran
receptor action of AT-II at the Usually well tolerated.
candesartan
antagonist angiotensin receptor.
(Peptide
analogue).

Verapamil,
Calcium They lower b.p by Agents such as
nifedepine,
channel decreasing peripheral diltiazem/verapamil have
amlodipine
blockers resistance negative inotropic action.

They induce diuresis that Thiazide diuretics cause

Chlorthiazide,
reduces plasma volume hypokalemia and also
Diuretics furosemide,
which in turn reduces C.O hyperglycemia in
spironolactone.
leading to a drop in b.p. diabetics.
They decrease sinus Myocardial insufficiency
rhythm, which leads to a Bradycardia Asthma
Metoprolol,
 Blockers decrease in heart rate, Heart block.
propranolol
which leads to a drop in Insulin dependent
b.p. diabetics.

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They block the action of

adrenaline at the a
 Adrenergic Prazosin, Impotence postural hypo
receptor present in blood
blockers terazosin tension
vessels thereby leading to
vasodilatation
The-nor methyl adrenaline
formed from methyldopa
Methyldopa
Central acts as false neuro Sedation, lethargy and
clonidine
sympatholytics transmitter on a2 and reduced mental capacity.
(h2 agonist)
decreases efferent
sympathetic activity.
Displaces N.T. from
Neurotransmitt Guanethedine
synapse increases
er depletors reserpine
N.T.metabolism
Hydralazine on prolonged
Vasodilatation leads to a use causes SLE
Hydralazine, decrease in peripheral (Systematic lupus
Vasodilators
minoxidil resistance, which in turn erythrematosus),
leads to fall in b.p. hirsustism, peripheral
pooling of blood.

Ethacyranic acid is contraindicated in Angina in Asthma B2 blockers is avoided.

ANTIHYPERLIPIDEMIC DRUGS:

These drugs lower the levels of lipoproteins and lipids in blood. The different types of
hyperlipoproteinemia are:

Elevated plasma
Type Disorder Elevated plasma lipids
lipoprotein
Cholesterol &
I Lipoprotein lipase deficiency Chylomicron
triglycerides
Familial
IIa LDL Cholesterol
hypercholesterolemia
Polygenic Cholesterol (moderate
IIb LDL (B-lipoprotein)
hypercholesterolemia increase)
Familial IDL, Cholesterol &
III
Dysbetalipoproteinemia chylomicron remnants triglycerides
VLDL
IV Hypertriglycereridemia Triglycerides
(pre-B lipoprotein)
Cholesterol &
V Hyperlipedemia VLDL, LDL
triglycerides

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THE CLASSIFICATION OF HYPOLIPEDEMIC DRUG IS AS FOLLOWS:

Class Drugs Mechanism of action Adverse effects

They inhibit the enzyme HMG-
HMG-CoA Lovastatin, CoA Reductase essential for the Headache, rise in
Reductase atorvastatin, conversion of HMG-CoA to serum transaminase,
inhibitors simvastatin mevalonate and thus inhibit rise in CPK levels.
synthesis of cholesterol.
These are ion exchange resins that
bind bile acids in the intestine Unpalatable and may
Bile acid Cholestyramine, inhibit their enterohepatic cause nausea,
sequestrants colestipol circulation. Cholesterol is absorbed flatulence, heartburn,
with the help of bile acids and in constipation.
their absence, it is excreted.
Increased appetite
They activate lipoprotein lipase
Clofibrate, and weight gain,
Fibric acid which is essential for the
Gemfibrozil, myalgia and
derivatives degradation VLDL resulting in
fenofibrate increased incidence
lowering of TG’s.
of gallstones.
Neomycin lowers LDL-CH by Neomycin may
Neomycin,
complexing with bile acids in the however damage
Others gugulipid
intestine. Guggul lipid probucol intestinal mucosa.
probucol
acts as Antioxidant Loose stools.

 Comniphora molmol – myrh (antiseptic),

 Comniphora mukul – guggul (antihyperlipedemic).
 Dromotropic – Drug affects conductivity of impulses in neuronal cells.

HORMONES

 They are mediator molecules act as chemical messengers.

 They are released in one part of the body & regulates activity of cells in other ports of Body.
 Hormones are secreted by endocrine or ductless glands.
 Most hormones enter interstitial fluid & then the Bloodstream.

M.O.A:- Hormones like, neurotransmitters, influence their target cells by chemically binding
to specific protein or glycoprotein receptors.

SITE OF ACTION:-

At cell membrane receptors – E.g.:- Adrenaline, glucagons, FSH, LH, TSH, ACTH
calcitonin, vasopressin, oxytocin, insulin etc.

At cytoplasmic receptors – E.g.:- steroidal Hormones.

At nuclear receptors – Thyroid Hormones.

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Down regulation: - when hormone is present in excess, the no. of target cells receptors
decreases. This makes target cells less responsive to the hormone.
Up regulation:- when there is a deficiency in hormone is the no. of receptors may increase.
This makes target cells more sensitive to hormone

Classification of hormones: - The endocrine glands include pituitary, Thyroid, Parathyroid,

Adrenal and pineal glands.
Water soluble hormones: - protein eicosanoid hormones.
Lipid soluble hormones: - Steroid, Thyroid & gaseous hormone (Nitric oxide).
Placental hormones: - Chronic gonadotropin – Prolactin, Estrogens – Progesterone,
Placental lactogen – Chorionic thyrotropin.

Hormones of the Anterior & Posterior Pituitary:-

Inhibiting
Releasing Hormone hormone
Hormone Secreted by
(stimulates secretion) (suppresses
secretion)
Growth harmone-
Human growth hormone Growth hormone-releasing inhibiting
(hGH) or somatotropin Somatotrophs hormone (GHRH) or hormone (GHIH)
(191aminoacid) somatocrinin (44A.A) or somatostain
(14AA)
Growth hormone-
Thyroid-stimulating
Thyrotropin releasing inhibiting
hormone (TSH) or Thyrotrophs
hormone(tripeptide) hormone
thyrotropin
somatostatin
Follicle-stimulating Gonadotrophic releasing
Gonadotrophs ---------
harmone (FSH) harmone(decapeptide)
Luteinizing harmone Gonadotrophic releasing
Gonadotrophs ---------
(LH) harmone
Prolactin
Prolactin (PRL)
Lactotrophs Prolactin releasing harmone inhibiting harmone
(198aminoacid)
or dopamine

Adrenocorticotropic
Corticotropin releasing
harmone (ACTH) or Corticotrophs ----------
harmone(41aminoacids)
corticotrophin

Mealanocyte-stimulating Corticotropin releasing

Corticotrophs Dopamine
harmone (191aminoacid) harmone

 Leuprolide is a synthetic non-peptide of GTRH.

 Dropamine antagonist not given in lactating women because it inhibits prolactin.
 Enuresis – Bed wetting (Desmopressin)
 Melatonin – (responsible for normal sleep)
 Posterior pituitary or neurohypophysis does not synthesize harmones; it stores and
releases two harmones oxytocin and antidiuretic harmones (vasopressin).

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HORMONE PRINCIPAL ACTIONS

Stimulates liver, muscle, cartilage, bone, and other tissues to
Human growth harmone synthesize and secrete insulin like growth factors. (IGF’s);
(hGH) or somatotropin IGFs promote growth of body cells, protein synthesis, tissue
repair, lipolysis, and elevation of blood glucose concentration.
Thyroid-stimulating
Stimulates synthesis and secretion of thyroid harmones by
harmone (TSH) or
thyroid gland
thyrotropin
In females, initiates development of oocytes and induces
Follicle-stimulating
ovarian secretion of estrogens. In males stimulates testes to
harmone (FSH)
produce sperm.
In females, stimulates secretion of estrogens and progesterone,
ovulation and formulation of corpus luteum. In males,
Luteinizing harmone (LH)
stimulates interstitial cells in testes to develop and produce
testosterone.
Prolactin (PRL) more
Together with other harmones, promotes milk secretion by the
active in presence of
mammary glands.
oxytocin
Adrenocorticotropic
Stimulates secretion of glucocorticoids (mainly coritsol) by
harmone (ACTH) or
adrenal cortex.
corticotrophin
Melanocyte-stimulating Exact role in humans is unknown but may influence brain
harmone activity, when present in excess, can cause darkening of skin.
Stimulates contraction of smooth muscle cells of uterus during
Oxytocin (OT) childbirth; stimulates contraction of myoepithelial cells in
mammary glands to cause milk ejection.
Conserves body water by decreasing urine volume; decreases
Antidiuretic harmone
water loss through perspiration; raises blood pressure by
(ADH) or vasopressin
constricting arterioles.

Pitutary harmone derivates:-

ANALOGUE USES
Bromocriptine Prolactin inhibitor Cancer therapy
Desmopressin ADH Diabetes insipidus
Gasrelin, coryntropin, Leuprolide ACTH Infantile spasms
Menotropins, urofollitin FSH, LH Infertility
Naferelin GNRH Cancer, Infertility
Ocreolide Somatostatin Inhibits glandular

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GONADAL HARMONES USES

Tamoxifen Breast cancer
Diethylstilbesterol After contraception
Estrogen & progesterone Oral contraception
Norgesterol & medroxyprogesterone chronic contraception
Mifepristone Abortifacient
Oxandralone Anabolic

THYROID GLAND

The follicular cells produce two harmones; thyroxine (tetraiodothyronine) and tri-
iodothyronine, which are known as thyroid harmones.

Synthesis and secretion of T3 and T4 occurs as follows:

a. Iodine trapping: Follicular cells trap iodine ions by an active transport

mechanism.
b. Synthesis of thyroglobulin: While the follicular cells are trapping iodide
ions, they are also producing thyroglobulin (TGB).
c. Oxidation of iodide: Iodine ions are oxidized by peroxidase to form iodine
(I2).
d. Iodination of tyrosine: as iodine molecules form, they react with tyrosines
that are part of thyroglobulin molecules. Binding of one iodine atom with
tyrosine yields mono-iodotyrosine (T1), while two iodine atoms yields di-
iodotyrosine (T2),
e. Coupling of T1 and T2: two T2 molecules combine to form T4 while one T1
and one T2 combine to form T3 in the presence of peroxidase.

Calcitonin: - It is a harmone produced by the parafollicular cells of the thyroid gland. It

decreases the level of calcium in blood by inhibiting the action of osteoclasts, the cells that
break down bone matrix.

Parathormone: - It is secreted by the parathyroid glands and it increases blood calcium and
magnesium levels, while it decreases phosphate levels.

The harmones produced by the adrenal cortex are of three types:

a. Mineral corticoids : Aldosterone
b. Glucocorticoids: Cortisol, Coorticosterone & Cortisone.
c. Androgens: Dehydroepidandrosterone.

The harmones produced by the chromaffin cell of the adrenal medulla are Epinephrine and
nor epinephrine.

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The four types of pancreatic islets that produce harmones are:-

1. A cells secrete glucagons.
2. B cells secrete insulin.
3. D cells secrete somatostatin.
4. F cells secrete pancreatic polypeptide.

Hormone Control of secretion Principal actions

Thyroid harmone Secretion is increased by Increase basal metabolic rate,
thyrotopin-releasing harmone stimulate synthesis of proteins, and
and high thyroid iodine levels increase use of glucose.
suppresses secretion.
Calcitonin High blood calcium levels Lowers blood levels of ionic calcium
stimulates secretion, low levels and phosphate.
suppresses secretion.
Parathyroid Low blood calcium levels Increases blood calcium and
hormone stimulate secretion; High blood magnesium levels and decreases
calcium levels inhibit secretion. phosphate levels.
Mineral corticoids
Increased blood K+ level and Increases blood levels of Na+ and
angiotensin II stimulates water and decrease blood level of K+.
secretion.
Glucocorticoids ACTH stimulates release. Increase protein breakdown stimulate
gluconeogenesis.
Androgens ACTH stimulates release. Assist in early growth of axillary and
public hair.
Epinephrine and Sympathetic preganglionic Produce effects that enhance those of
Nor epinephrine neurons release acetylcholine, the sympathetic division of the
which stimulates secretion. automatic nervous system during
stress.
Glucagon Decreased blood level of Raises blood glucose level by
glucose, exercise and mainly accelerating breakdown of glycogen
protein meals stimulate into glucose in liver.
secretion.
Insulin Increased blood level of glucose, Lowers blood glucose level by
acetylcholine, arginine and accelerating transport of glucose into
leucine, glucagon, GIP, hGH, cells, converting glucose into
and ACTH stimulate secretion. glycogen and stimulates protein
synthesis.
Somatostatin Pancreatic polypeptide inhibits Inhibits secretion of insulin and
secretion. glucagon and slows absorption of
nutrients from the gastrointestinal
tract.
Pancreatic Meals containing protein, Inhibits somatostatin secretion,
polypeptide fasting, exercise, and acute gallbladder contraction, and secretion
hypoglycemia stimulate of pancreatic digestive enzyme.
secretion.

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Hormones affecting calcium homeostasis:-

 Calciferol (25 Hydroxy Vit-D3)
 Calcitrol (1, 25 dihydroxy Vit-D3)
 Cholecalciferol (Vit-D3)
 Secalcifediol (24, 25 dihydroxy vitD3)
 Ergocalciferol (VitD2)
 Androgens: - Testosterone, Oxandrolone, Stanozolol.
 Antiandrogens: - Finasteride (synthetic inhibitors).
 Antiprogestins: - Mifepristone.

USEFUL TIPS

 WELCOME TO PHARMAROCKS
 THESE ARE THE MOST IMPORTANT NOTES OF
PHARMACOLOGY
 IT COVER GENERAL PHARMACOLOGY, ANS, CNS AND CVS
 REVISE THIS DAILY FOR THE PROPER PREPARATION
 DRUG CLASIFICATION, MOA, SIDE EFFECTS, USE , COVER
UNDER THIS
 THIS NOTES ALWAYS HELPS U IN GPAT AS WELL AS DURING
YOUR SEMESTER EXAMS U CAN PREPARE FROM THIS.
 IF POSSIBLE TAKE THE PRINT OUT THIS AND REVISE
REGULARLY TO IMPROVE YOUR KNOWLEDGE FOR
PHARMACOLOGY

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CHEMOTHERAPY MASTER GPAT NOTES

It deals with the use of chemical agent to arrest the progress of infectious diseases by destroying infective parasites or microbes without
damaging the host tissues.

M.O.A:-
1. INHIBITING PROTEIN SYNTHESIS BY BINDING TO RIBOSOMAL SUBUNIT & DESTROYING THE BACTERIAL CELL.
E.g.:- Gentamycin & streptomycin.

2. REVERSIBLE INHIBITION OF PROTEIN SYNTHESIS BY ACTION ON RIBOSOME.

E.g.:- Broad spectrum Antibiotics.

3. BY DETERGENT ACTION (LEAKAGE OF CELL CONSTITUENTS)

A. Direct cell membrane. E.g.:- Colistin, Polymyxin
B. Drug binding to cell wall sterols. E.g.:- Nystatin, Amphotercin.

4. INHIBITION OF CELL WALL SYNTHESIS: -

E.g.:- Penicillins, Cephalosporins, sulphonamides.

5. DRUGS AFFECTING NUCLEICACID METABOLISM:-

A. Inhibition of DNA dependent RNA polymerase. E.g.:- Refampicin.
B. Inhibition of DNA supercoiling & DNA synthesis. E.g.:- Quinolones & Fluoroquinolones.

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DRUG RESISTANCE:-
1. Natural: - Organisms do not have target sit for drugs to act. E.g.:- Antifungals in Bacterial infections.
2. Acquired: - Organisms are exposed to the drug in such a manner that it develops resistance.

Cross resistance: -
Development of resistance to one substance may also show resistance to another substance to which the organism has not been exposed.
E.g.:- resistance between Sulphonamides, resistance between Tetracycline’s, resistance between Tetracycline’s & Chloramphenicol.
There is no cross resistance between Animoglycosides.

Super infection/Supra infection: -

 It is due to the use of Broad spectrum antibiotics.
 There is no. of microorganisms inhabiting GIT & these organisms constitute the microbial flora. They are called as “commensals” under
normal conditions; these organisms compete with another for nutrients. & therefore they are unable to proliferate rapidly.
 When a Broad spectrum antibiotic such as chloramphenical / tetracycline is administered, it might kill most of the microbial flora barring
a few organisms. Now these few microbes are free to proliferate rapidly in the absence of competition & they multiply, spread all over
the body & cause infections called super infections.

Antimicrobial agent: - An agent which kills M.O. or suppresses their growth. The susceptibility of AMA is determined by
1. Radiometric method
2. Resistance ratio method (Traditional).
Sulfonamides & Sulfones
These are derived from prontosil red (dye) & are effective against pyogenic Bacterial Infections.

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CLASSIFICATION:-
1. Short acting: - Sulfadiazine, Sulfisoxazole.
2. Intermediate: - Sulfamethoxazole.
3. Long acting: - Sulfadoxine, Sulfamethopyrazine.
4. In intestinal infections: - Sulfasalazine.
5. In Burn therapy: - Silver sulfadiazine, mafenide.
6. In ophthalmic infection: - Sulfacetamide.

M.O.A:-

Guanosine…………> PABA _______> Dihydropteroic acid

Several steps (-) Sulfonamides (-) Trimethoprim <……………___________Dihydrofolic acid folate reductase folic acid

DIHYDRO FOLATE REDUCTASE

 Tetrahydrofolic acid ------------N5, N10 methylene FAH4
 N5formylFaH4 -------- N10 formyl FAH4
 N5formylFAH4, N5N10 methylene FAH4, N10formyl FAH4 is very essential for several Biosynthetic pathways in humans & Bacteria.
 The growth and cell division in bacteria can be stopped if any drug blocks Biosynthesis of folate co-enzymes.
 Folate co-enzymes are biosynthesized from dietary folic acid in humans & other animals.
 Sulfonamides act as competitive inhibitors for the incorporation of PABA to form Dihydropteroic acid.
 Trimethoprim is an inhibitor of dihydrofolate reductase required for the conversion of dihydrofolic acid in to tetrahydrofolic acid in
bacteria.

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Mechanism of resistance: - It may be due to

1. Increased production of PABA by resistant bacteria
2. Decrease the affinity of folate synthetase enzyme for sulfonamides.
3. Adopts an alternative pathway in folate metabolism. E.g.:- gonococci, pneumococci, E.coli, S.aureus etc

Cotrimoxazole: - fixed dose combination of trimethoprim and sulfamethoxazole in a ratio of (1:5). As this inhibits 2 different steps in pathway,
the development of resistance is reduced.

Adverse reactions:-
1. Stevens Johnson’s syndrome
2. Hemolytic anemia
3. Kernicterus (neonatal Hyperbilirubinemia)
4. Skinrash, Urticaria
5. Crystalluria is due to crystals of sulfanilamide, This can be presented by
i) Alkalanizing the urine
ii) By increasing the urine flow
iii) By reducing PKa of drug.
Metabolism: - It occurs by acetylation at N4 they are excreted as mixtures of unmetabolised drugs, N4 acetates & glucouronides.
Sulfones: - less active than sulfonamides
M.O.A:- similar to sulfonamides. E.g.:- Dapsone

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QUINOLONES

E.g.:- Nalidixic acid

Fluoroquinolones: - These are more potent than quinolones.
First generation: Norfloxacin, Ofloxacin, Ciprofloxacin, Perfloxacin.
Second generation: Sparfloxacin, Lomefloxacin.

M.O.A:- They inhibit Bacterial DNA gyrase (An enzyme responsible for introducing negative supercoiling in to circular duplex DNA.)
Negative super coiling relieves the tortional stress of unwinding helical DNA & thereby allows transcription & replication to occur. Humans
have Topoisamerase II in place of gyrase & this accounts for the low toxicity of FQ’s to the host cells.

Resistance: - Due to chromosomal mutation producing a DNA gyrase with reduced affinity for FQ's.
AR: - Hypersensitivity reactions, Hemolytic anemia GI disturbances.
Uses: - Typhoid, soft tissue infection, UTI.

B Lactam Antibiotics
E.g.:- Pencillins & Cephalosporins

M.O.A:- microorganism synthesize two pentapeptides –

1. UDP-N-acetyl muramic acid (NAMA)
2. UDP-N-acetyl glucosamine (NAGA)

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These peptidoglycon residues are linked together in forming long strands & the UDP is split off. The final step is cleavage of the terminal D-
Alanine by ‘transpeptidase’. The energy released is utilized for establishment of crosslinkages between peptide chains of the neighbouring
strands.

Beta lactam Antibiotics inhibit the enzyme ‘transpeptidase’ so that crosslinking does not take place. These enzymes constitute the pencillin
binding proteins which are located in the bacterial cell membrane. When Bacteria divide in presence of a B-lactam antibiotic cell wall deficient
forms are produced & these forms burst resulting in cell lysis.
Blood, pus & tissues fluids do not interfere with the antibacterial action of B-lactam Antibiotics.

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CLASSIFICATION OF PENICILLIN’S:-
 Natural: - Penicillin-G, procaine penicillinG
 Acid resistant: - Penicillin V (phenoxymethyl penicillin)
 Broad spectrum: - Ampicillin, Amoxicillin, Piperacillin Methicillin
 B lactamase inhibitors: - clavulonic acid, sulbactam
 Monobactams: - Aztreonam
 Carbapenems: - Imipenam, Thienamycin

BACTERIAL RESISTANCE: -
Gram positive organisms develop resistance by producing B-lactamases. (Opens B lactam ring & inactivates) In methicillin resistant S.aureus the
penicillin Binding proteins has been mutated. So that it does not binds methicillin efficiently.
AR: - penicillin allergy due to formation of Antigenic penicilloyl proteins.
Jarisch-Herxhemier reaction is Syphilis patient.
Degradation of penicillin can be controlled by adjusting the PH of aq-solutions between 6.0 – 6.8.

USES: -
Gonorrhea, Syphilis, Diphtheria & coccal infections.
Augmentin = Clavulanic acid + Amoxicillin
Unasyn = Sulbactam + Ampicillin

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CLASSIFICATION OF CEPHALASPORINS:-
Cephalosporin = B lactam ring + dihydrothiazine ring
Penicillin = B lactam ring + thiazolidine ring.

I II III IV

Oral Cephalexin Axetal Cefaclor Cefuroxime Cefixime Cefpodoxime ---

Parentral Cephadroxil Cefomandole Cefonacid Cefotoxime Ceftriaxone Cefepime

Antipseudomonal Cephalosporins: -
Cefoperazone, Moxalactam, Cefotaxime, Ceftizoxime & Ceftriaxone.

Disulfiram effect: -
Cefomandole, cefoperazone, cefometazone, cefotetan & moxolactam due to tetrazole group produce Disulfiram effect when taken with alcohol.
Aztreonam is used to treat hospital acquired infections (Nosocomical infections).

Tetracyclines, Chloramphenicol, Aminoglycoside and Macrolide antibiotics

In order to understand the mechanism of the above antibiotics it is essential to understand the process of protein synthesis:
 On a specific signal from the cytoplasm, the DNA in the nucleus unwinds itself with the help of the enzyme DNA gyrate or
topoisomerase (humans).

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 One of the strands of the DNA acts a template for the synthesis of a complimentary strand of mRNA in the presence of RNA
polymerase. The synthesis of mRNA from DNA is called transcription.
 The mRNA which now contains the code for protein synthesis comes out of the nucleus and attaches itself to the 30’s ribosomal subunit.
 This is followed by the attachment of the 50’s ribosomal subunit to the mRNA-ribosomal complex.
 There are two sites present on the 50’s ribosomal subunit, the acceptor site and the peptidyl site.
 Protein synthesis does not begin until the mRNA has the initiator codon AUG (codes for formylmethionine) on it.
 Once the mRNA exposes the initiator codon AUG, a specific tRNA carrying the amino acid formylmethionine will arrive at the
acceptor site of 50’s subunit.
 The tRNA carrying the amino acid is now transferred to the peptidyl site where the tRNA dissociates leaving the amino acid at
the peptidyl site.
 The ribosome now moves along the mRNA to expose the next coon.
 Depending upon the codon the corresponding amino acid is brought to the acceptor site by a specific tRNA.
 The tRNA carrying the amino acid is now transferred to the peptidyl site where the tRNA dissociates leaving the amino acid at
the peptidyl site.
 Again, the ribosome now moves along the mRNA to expose the next codon and this process continues until the mRNA shows one
of the terminatory codons UAA or UAG or UGA. These terminatory codons are called non-sense codons, as they do not code for
any particular amino acid.
 The transfer of data contained in the mRNA to form proteins is called translation.
 When only one ribosome is attached to the mRNA it is called monosome when there are more than one ribosome attached to the
mRNA it is called polysome.

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Antibiotic Tetracycline Chloramphenicol Aminoglycoside Macrolide

Soil actinomycetes
Source Streptomyces Venezuelae Streptomycin- S.griseus Erythromycin- S.erythreus
S.aureofaciens
Spectrum of Active only against aerobes. Active against mainly gram +
Broad spectrum Broad Spectrum
activity Bactericidal organisms.
It binds to the 30’s subunit,
the 50’s subunit as well to the
30s-50s interface. They
freeze initiation of protein It combines with 50s ribosomal
It acts by interfering with the
synthesis, prevent polysome subunit and interferes with
Binds to the 30’s transfer of the elongating peptide
formation. Binding to the translocation of the elongated
ribosomal subunit and chain to the newly attached
30s-50s interface causes peptide chain back to the
Mechanism inhibits the attachment amino acid at the ribosome
distortion of the mRNA peptidyl site. The ribosome fails
of action of aminoacid-tRNA mRNA complex. Therefore, it
codon resulting in wrong to move along the mRNA to
complex to the mRNA- inhibits peptide bond formation.
amino acids entering the expose the next codon and thus
ribosomal complex. It specifically attaches to 50’s
peptide chain and these protein synthesis is terminated
ribosome.
defective proteins affect the prematurely.
integrity of the cell
membrane resulting in cell
death.

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A. Inactivating enzymes
Due to plasma mediated that adenylate/acetylate or
synthesis of a phosphorylate the Resistant organisms produce
Resistant organisms produce
protection protein that antibiotic. erythromycin esterase that
Mechanism Chloramphenicol acetyl
protects the ribosomal B. Decrease in the affinity inactivates the drug or the
of Resistance transferase, which inactivates the
binding site from TC’s. of the ribosomal protein organisms become less
drug.
Posess cross resistance that binds the antibiotic. permeable to the drug.
with chloramphenicol. C. Porins become less
permeable to the drug.

TC’s have chelating

property- form
Oral form is Chloramphenicol All ionize in solution and are Erythromycin is acid labile. To
Pharmacokin insoluble and
palmitate. Parenteral form is not absorbed orally. Excreted protect it from the gastric acid it
etics unabsorbable
Chloramphenicol Succinate. unchanged in urine. is given an enteric coat.
complexes with calcium
and other metals.

Adverse a. Liver damage a. Gray baby syndrome: seen in a. Ototoxicity a.Gastrointestinal distress
Effects b. Kidney damage infants because they lack the  Cochlear damage
Fanchony c. Photo toxicity glucoronic acid required for  Vestibular damage a. Hepatitis.
syndrome. d. Deposition of conjugation with b. Nephrotoxicity

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Shown by calcium tetracycline Chloramphenicol. c. Neuromuscular

only chelate in bones and b. Super infections blockade
doxycycline teeth. c. Bonemarrow depression-
e. Vestibular toxicity- aplasticanemia,
Ataxia, vertigo and agranulocytosis,
nystagmus thrombocytopenia.
(involuntary eye
ball moment).
f. Diabetes insipidus-
Demeclocyclin

a. Used to treat
infections, when the a. Tuberculosis
a. Typhoid (enteric fever) a. Atypical pneumonia caused by
causative organism is b. SABE
b. H.influenzae meningitis mycoplasma pneumoniae
Uses unknown. c. Plague
c. Anaerobic infections b. Diphtheria, tetanus, Syphilis,
b. venereal diseases d. Tularemia sub acute
D.Intraocular infections. etc...
c. Cholera, plague, Bacterial endocarditis (sabe)
Brucellosis, etc.

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Tetracyclines:-
More stable & long acting ------ 6-deoxy tetracycline, methacycline, doxycline minocycline.

Miscellaneous Antibiotics:-

1) Lincosamide antibiotics: - clindamycin M.O.A & spectrum of activity is similar to erythromycin & also exhibits partial cross resistance.
2) Glycopeptide Antibiotics: - E.g.:- Vancomycin acts by inhibiting cell wall synthesis. It binds to the terminal dipeptide sequence of
peptidoglycon units at the cell membrane & their cross linking to form the cell wall does not take place.
Uses: - In MRSA infections.
3. Polypeptide Antibiotics: - Bactericidal agents have detergent like action on cell membrane. They have high affinity for phospholipids &
thus they orient between phospholipid & the protein layers in gram negative organisms, resulting in formation of pseudopore. As a result
aminoacids leak out leading to cell death. E.g.:- Polymyxin B, Bacitracin, Colistin, Thyrotricin, Capreomycin, Nespirocin.

Urinary Antiseptics: - Nitrofurantoin, Hexamine

Urinary Analgesic: - Phenazopyridine HCL.

ANTITUBERCULAR AGENTS

Tuberculosis is caused by mycobacterium tuberculosis.

First line drugs: - INH, Rifampicin, Pyrazinamide, Ethambutol.
Second line drugs: - Ciprofloxacin, Azithromycin.

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DRUG M.O.A PHARMACOKINETICS A.R

It undergoes Acetylation At lowPH-

P-amino salicylic
Prevents incorporation of PABA decarboxylation Hypersensitivity reactions
acid
At highPH-oxidation

Inhibits the synthesis of mycolic acid

Peripheral neuritis due to renal excretion of
INH (imp component of mycobacterial cell Acetylated by liver.
vit B6 ,Hepatitis
wall)

Hepatitis respiratory syndrome, Cutaneous

Inhibits DNA dependent RNA Metabolized in liver to an active
Rifampicin syndrome, Flu syndrome, Abdominal
polymerase deacteylated metabolite.
syndrome.

Not known penetrates inflamed

Hepatatoxicity, Hyperuricaemia (due to
Pyrazinamide meninges in treatment of tuberculosis Penetrates CSF & metabolised in liver.
inhibition of uric acid tubular secretion)
meningitis.

Ethambutol Interferes with mycolic acid

75% of oral dose is absorbed & Loss of visual acuity, field effects due to
(d isomer is more incorporation in cell wall & inhibits
temporarily stored in R.B.C. optic neuritis.
patent) RNA synthesis.

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Antitubercular Antibiotics: - Cycloserine, Capreomycin, Viomycin, Rifampicin.

Effective treatment :- (Sterilization period).

INH 300mg, Rifampicin 600mg, Pyrazinamide 25mg/kg (for 8 weeks)
(Maintainance period) INH & Rifampicin (for 16 weeks)

ANTILEPROTIC AGENTS

Leprosy is called by Mycobacterium leprae.

Drug M.O.A Pharmacokinetics A.R

Completely absorbed orally, gets Mild Hemolytic anemia,

Dapsone Inhibits incorporation of PABA in to folic acid
concentrated in skin, liver & kidney. gastric intolerance.

Inhibits bacterial cell wall synthesis by inhibiting the

Cycloserine enzyme that racemises h-alanine and links two D-
Alanine residues.

Binds with nucleic acids & concentrate in Well tolerated reddish

Clofazimine Gets accumulated in tissues
reticuloendothelial tissue & interfere with template Block discolouration of
(dye) especially in crystalline form.
function of DNA. skin

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ANTIFUNGAL AGENTS
Classification:-
1. Azoles: - Clotrimazole, Ketaconazole, Miconazole.
2. Allylamine & related compounds: - Tolnafate, Terbinafine.
3. Fatty acids: - Propionic acid, Triacetin, Salicylic acid.
4. Phenol & their derivatives: - Haloprogin, Cyclopirox.
5. Nucleosides: - Flucytosine.
6. Antibiotics: - Nystatin, Amphotericin, Candidicin.
7. Heterocyclic Benzofuran: - Griseofulvum.

Drug Amphotericin B Griseofulvin Imidazoles & triazoles. Flucytosine Tolnafate

Mechanism Has high affinity for It interferes with They inhibit the fungal It is taken up by fungal Interfere with fungal
of action ergosterol present in mitosis and causes cytochrome P450 enzyme cells and then converted ergosterol Biosynthesis
fungal cell membrane. abnormal metaphase lanosterol 14- into 5-FU and then to 5- by epoxidation of
Binds to it forming a configurations. The demethylase required for fluorodeoxyuridylic acid squalene by the enzyme
micropore, through daughter nuclei fail to conversion of lanosterol which is an inhibitor of squalene epoxidase.
which amino acids move apart and thus to ergosterol. This thymidylate synthetase
leak out leading to cell cell division is arrested results in membrane required for the
death. at metaphase. abnormalities in the synthesis of thymidylic
fungus. acid, which is a
component of DNA.

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Spectrum Candida albicans, Dermatophytes such as Dermatophytes, candida Cryptococcus Dermatophytes candida.
of activity Histoplasma Epidermophyton, albicans, nocardia, neoformans, candida,
capsulatum, etc. Trichophyton, leishmania, etc. torula, aspergilllus,
microsporum, etc. chromoblastomyces.
Pharmacoki Administered both Gets deposited in the Administered orally
netics orally and Keratin forming cells of
prarenterally. skin, hair and nails.
Absorption is enhanced
by micronisation.
Adverse Nephrotoxicity- Peripheral neuritis, Inhibits CYP3A4, Leucopenia,
effects azotemia, reduced transient leukopenia, thereby raising the blood thrombocytopenia.
g.f.r acidosis. albuminuria. levels of drugs like
warfarin, terfenadine.
Uses Systemic mycoses and Dermatophytosis. Systematic and topical Chromoblastomycosis. Athlete’s foot
Leishmaniasis. infections. ringworm.

Antiviral agents: Infectious virus particle is called virion. DNA containing virus
Adenovirus Many types Respiratory tract & eye infections
Herpes virus H.simplex I & II vercilla zoster Herpes zoster Encephalitis chicken pox shingles
Papora virus Human wart virus polyoma virus Human wart salivary gland infection
Pox virus Vaccine Small pox, chicken pox, cow pox, eczema.

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RNA CONTAINING VIRUS:-

Orthomyxovirus Influenza A,B,D Influenza A,B,D

Picornovirus Rhinovirus Respiratory disease poliomyletis

Retrovirus Type C Leukemia

Type B Mammary tumor
Type D Monkey Aids
HIV AIDS
Rhabdovirus Rabies virus Rabies

Togavirus Rubella virus Rubella

Unclassified virus Hepatitis A,B,&C viruses Hepatitis

CLASSIFICATION:-
A. Anti-herpes virus. Most of the antiviral drugs of this class act by inhibiting DNA polymerase. E.g.:- Idoxuridine, acyclovir,
Ganciclovir, Foscarnet.
B. Anti-retro virus. Non-nucleoside reverse transcriptase inhibitors. E.g.:- Zidovudine (AZT), Didanosine, and Zalcitabine.
Nevirapine, Delaviridine.
Protease inhibitors. E.g.:- Saquinavir, Indinavir.
C. Anti-influenza virus. E.g.:- amantadine.
D. Others. E.g.:- interferons, ribavirin.

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Drug Mechanism of action Mechanism of resistance Adverse effects Uses

It is phosphorylated by viral
thymidylate kinase to monophosphate, Resistant viruses decrease
then to triphosphate. The triphosphate the amount of thymidylate
is an inhibitor of viral DNA kinase required for the 1. H.simplex
Idoxuridine polymerase, causing inhibition of viral activation of the drug. keratoconjuctivities.
DNA synthesis and it is also Decrease in the affinity of (Cytomegalblasto virus)
incorporated in the DNA resulting in DNA polymerase for the
faulty DNA, which code for wrong drug.
proteins.

A phosphonoformate derivative binds

to the pyrophosphate binding sites of Hypokalemia,
CMV retinitis, varicella
Foscarnet viral DNA polymerase and reverse hypomagnesia, renal
zoster infections.
transcriptase to prevent the toxicity.
incorporation of nucleotides into DNA.

On phosphorylation in the body into

zidovudine triphosphate, it inhibits the Decrease in the affinity of Anaemia,
Zidovudine,
enzyme viral reverse transcriptase reverse transcriptase for the neutropenia, AIDS
Stavudine
which is required for the synthesis of drug. myopathy.
DNA from viral RNA.

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An aspartic enzyme protease encoded

by HIV is involved in the production of G.i.t intolerance,
structural protein and enzymes of the asthenia, paresthesia Used to treat later stages
Saquinavir
virus. Inhibition of the aspartic enzyme and exacerbation of of AIDS infections.
by Saquinavir will deprive the virus of diabetes.
the essential proteins.
It acts on an ion channel M2 and Insomnia, dizziness,
Amantadine influenzaA2, Parkinson’s.
interferes with the step of uncoating. hallucination.
Its mono and triphosphate derivatives
Ribavirn InfluenzaA & B, measles.
inhibit GTP and viral RNA synthesis.
Converted to monophosphate by viral
Acylclovir Herpes infections.
thymidine kinase.

Interferons: - are the cytokines produced by the body in response to viral infections. They bind to cell specific receptors and interfere with
various stages of viral replication such as uncoating, penetration of virus into the host cell, synthesis of viral protein. Interferon’s bind to
receptors and induce production of Interferon induced protein that has antiviral effects. They are active against both DNA & RNA viruses. They
are host specific. They are indicated for:-
 Chronic hepatitis B & C
 AIDS related Kaposi sarcoma (cancer & aids)
 Hairy cell leukemia.
 Rhinoviral cold.
Adverse effects include myelosupression, neurotoxicity, etc.

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ANTIMALARIAL AGENTS

Malaria is caused by four species namely

1. plasmodium vivax,
2. P.falciparum,
3. P.malariae and P.ovale.
4. P.falciparum does not have secondary Schizontic stage.

CLASSIFICATION:-

1. Cinchona Alkaloids: - Quinine

2. 4 Amino quinoline: - Chloroquine, Amodiaquine
3. 8 Amino quinoline: - Primaquine, pamaquine
4. 9 Amino Acridines: - Quinacrine
5. Biguanides & dihydrotriazines: - Chlorguanide
6. Pyrimidines: - Pyrimethamine
7. Sulfonamides: - Sulfadoxine, Dapsone, Sulfamethopyrazine
8. Quinoline methanol: - Mefloquine
9. Phenanthrene methanol: - Halofantrine
10. Miscellaneous: - Qinghaosu, tetracycline’s.

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DRUG CHLOROQUINE MEFLOQUINE QUININE CHLOROGUANIDE

PROGUANIL
Mechanism It moves into acidic vesicles of Inhibits the enzyme haem Inhibits the enzyme It is cyclised in the body to a
of action the parasite, raises pH and polymerase. haempolymerase. triazine derivative, which inhibits
inhibits the degradation of plasmodial dihydrofolate
Hemoglobin by Iysosomal reductase, which is essential for
products. It inhibits the enzyme the synthesis of folate
haempolymerase that coenzymes.
polymerizes toxic free haem to
nontoxic haemzoin.
Resistance It occurs due to the increased
Increased expression of Increased expression of an It occurs by mutation resulting in
efflux of the drug from thean efflux transporter efflux transporter similar to decrease in the affinity of the
parasitic vesicles. similar to human human transporter, P- DHFRase for drug.
transporter, P- glycoprotein.
glycoprotein.
Spectrum of Erythrocytic stages of all the Blood Schizonticide Blood schizonticide on all the Slow acting Erythrocytic
activity four plasmodial species. Against P.Falciparum & four plasmodial species. Schizonticide.
P.vivax.
Adverse Liver damage. Gastrointestinal Cinchonism-tinnitus, Mild abdominal upset, hematuria.
effects disturbance, giddiness, paraplegia, metallic taste.
insomnia. Prolongation Cardiac arrhytmias, blood
of QT intervals leading to dyscriasis can also occur.(bone
arrhythmias. marrow depression)

Uses Also active Entamoeba Treatment of an acute Resistant falciparum malaria, Prophlaxis of malaria.
histolytica & Giardia lamblia. attack. cerebral malaria.

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 Pyrimethamine also acts by inhibiting plasmodial dihydrofolate reductase and it is a more potent than chlorguanide.
 Primaquine acts on the exoerythrocytic stages and is highly active against the gametocytes and hypnozoites.
 It causes hemolytic anemia in patients with G6-PD deficiency.
 Halofantrine, a blood schizonticidal agent is active against multiresistant.
 P.falciparum. Cross-resistance is seen between Halofantrine and mefloquine.
 Artemesinin, a sesquiterpine lactone is active against multiresistant.
 P.falciparum. It acts by interacting with haem and generated free radicals that binds to the membrane proteins and damages the parasite.

ANTIAMOEBIC DRUGS

Ameobiasis is a protozoal disease caused by Entamoeba Histolytica.

Intestinal amoebiasis: - Here E.Histolytica invade the intestinal wall of the colon.
Extra intestinal amoebiasis: - It affects liver, lungs & Brain.
E.Histolytica exists in two forms
1. Cysts: - inactive form
2. Trophozite: - active form

CLASSIFICATION:-
A. Tissue amoebicides
 For both intestinal and extra intestinal amoebiasis. Nitroimidazoles. E.g.: Metronidazole, tinidozole rhimostrozole. Alkaloids. E.g. :
emetine
 For extra intestinal amoebiasis only. E.g. : chloroquine

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B. Luminal amoebicides
 Amide. E.g. : Diloxanide furoate
 8-Hydroxyquinolines. E.g.: Quiniodochlor, Diiodohydroxyquin clioquinol.
 Antibiotics. E.g.: Tetracycline’s.

Drug Metronidazole, tinidozole Emetine Diloxanide furoate Quiniodochlor, Diiodohydroxyquin

Mechanism The nitro group of the compound It inhibits protein by It prevents the formation Kill the cyst forming trophozoites in
of action is reduced to intermediate arresting the intraribosomal of cysts. From the intestinal tract by chelating ferrous
compounds that cause cytotoxicity translocation of peptidyl trophozoites. Interferes ions which are essential for protozoal
by damaging DNA. tRNA aminoacid complex. with protein synthesis. metabolism.

Spectrum Anaerobic organisms. Kills trophozoites but has no Kills trophozoites Active against entamoeba, Giardia
of activity action on cysts. responsible for cyst trichomonas and some fungi.
formation.
Adverse G.i.t disturbances, CNS Hypo tension, tachycardia, Flatulence, itching is Iodism. Prolonged use caused ‘sub
effects symptoms. ECG changes and occasional. acute myelopatic neuropathy’
myocarditis. (SMON).
Uses Amoebiasis, Giardiasis, Liver fluke infestation Asymptomatic amoebiasis. Amoebiasis, Giardiasis, monolial
Ulcerative gingivitis, H.Pylori vaginitis, fungal infections.
infections.

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Suramin sodium: - anionic in nature & binds with cationic sites in proteins & enzymes in glycolytic pathway.

Sodium stilbogluconate: - These pentavalent antimonials get converted to trivalent antimonials, which inhibit phosphofructokinase, an enzyme
catalyses a limiting step in glycolysis.

Leishmaniasis is caused by Leishmania donovani and the drugs used to treat are Sodium Stilbogluconate, Meglumine, pentamidine,
Amphotericin B, Ketoconazole and allopurinol. Severe form of leishmaniasis is Kala-azar.

ANTHELMINTICS

These agents destroy or eliminate parasitic worms (helmints) from GIT/body tissues.

Anthelmintic may act as:-

1) Vermifuge :- expels worms by paralyzing them
2) Vermicide :- kill worms in the body
3) Some may also impair the egg production process in worms.

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Drug Mebendazole/Albendazole Pyrantel pamoate Piperazine Diethyl carbamazine

Inhibit glucose uptake, It causes activation of nicotinic It causes neuromuscular
Alteration of the
thereby depleting glycogen cholinergic receptors in the worm blockade by antagonizing Ach
Microfilariae (MF)
Mechanism stores. Bind with affinity to resulting in persistent action and causes
membrane so that they are
of action micro tubular protein B- depolarization, which leads to hyperpolarisation, which leads
readily phagocytosed by
tubulin and inhibit its paralysis. Worms are then to paralysis. Worms are then
tissue fixed monocytes.
polymerization. expelled. expelled.

Round worm, hook worm,

Spectrum of Hook worm Round worm, thread Mf of Wuchereria bancrofti,
tirichuriasis, pinworm & Round worm,
activity worm. Brugia malayi, o.volvulus.
guinea worm.

Drug Levamisole Niclosamide Praziquantel Ivermectin

Causes leakage of intracellular
It inhibits oxidative
calcium from the membranes Potentiation of GABAergic
Mechanism It is an immunomodulator- phosphorylationin mitochondria
leading to paralysis. The lose transmission in worms
of action restores T-cell function and thereby interferes with
grip of the intestine and are leading to paralysis.
anaerobic generation of ATP.
expelled.

Spectrum of Ascaris & stronglyloides Taenia saginata, T. solium, Onchocerca volvulus, which
Tape worms schistosomiasis.
activity larvae. hymenlepsis nana. causes river blindness.

Thiabendazole acts by inhibiting fumarate reductase. In T.C.A. cycle useful in strongylodias.

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ANTICANCER AGENTS
These are cytotoxic drugs either kill cancer cells or modify their growth cell cycle:
G1 (pre-synthetic phase)

S – Synthesis of DNA

G2 – Post synthetic phase

M - Mitosis phase
 
G1 G1 (daughter cells)

G0 – Resting phase

 The cells in resting stage are those that are non-proliferating.

 These remain quiescent, but they can be recruited in the cell cycle when stimulated later.
 Cytotoxic drugs are either cell cycle specific or cell cycle non-specific (they kill both resting as well as dividing cells).
o Cytotoxic drugs that are cell cycle specific include drugs like Methotrexate, Cytarabine, 6-Mercaptopurine, 6-Thioguanine,
Mitomycin, Doxorubicin act on the S phase, drugs like Daunorubicin, Bleomycin, etoposide that act on the G2, drugs like
vincristine, Vinblastine and paclitaxel that act on the M phase.
o Cytotoxic drugs that are cell cycle nonspecific include nitrogen mustards, cyclophosphomide, Chlorambucil, 5-FU, L-asparginine,
Cisplatin, Procarbazine, Dacarbazine, etc.

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CLASSIFICATION:
A. Alkylating agents: These can be further classified into:
a. Nitrogen mustards. E.g.: Mustine, Cyclophosphamide, Ifosfamide, chlorambucil
b. Ethyleneimine. E.g.: Thiotepa
c. Alkylsulfonate. E.g.: Busulphan
d. Nitrosourea. E.g.: Carmustine, Lomustine (they cross B.B.B & used in Brain tumors)
e. Triazine. E.g.: Dacarbazine.
f. Hydrazine. E.g.: Procarbazine

B. Antimetabolites
a. Folate antagonist. E.g.: Methotrexate (amethopterin)
b. Purine antagonist. E.g.: 6-Mercaptopurine, Azathiopurine, 6-Thioguanine
c. Pyrimidine antagonist. E.g.: 5-Fluorouracil, Cytarabine.

C. Vinca alkaloids. E.g.: Vincristine (oncovin), Vinblastine.

D. Taxanes. E.g.: paclitaxel, Taxotere.

E. Epipodophyllotoxin. E.g.: etoposide, Teniposide Daunorubicin.

F. Antibiotics. E.g.: Actinomycin D (Dactinomycin), Doxorubicin Bleomycins, Mitomycin.

G.Miscellaneous. E.g.: cisplatin, L-asparaginase.

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TOXICITY OF ANTICANCER DRUGS:-

They have a profound effect on rapidly proliferating cells, the most important target of action are the nucleic acids and their precursors; rapid
nucleic acid synthesis occurs during cell division. The different Toxicities that arise from Anticancer agents are:-
1. Bone marrow depression (Myelo suppression / Blood dyscriasis) resulting in granulocytopenia, agranulocytosis, thrombocytopenia,
Aplastic anemia
2. Lymphocytopenia and the suppression of Humoral & Cell mediated immunity.
3. Stomatitis, diaarohea, shedding of mucosa, hemmorages
4. Skin: Alopecia
5. Inhibition of gonadal cells causes oligozoospermia& impotence in males.
6. Teratogenic in nature.
7. Hyperuricaemia

Virus: - Epstein barr virus is responsible for production of cancer

Genes: - Oncogene is responsible for production of cancer

ALKYLATING AGENTS: -
 These compounds produce highly reactive carbonium intermediates, which transfer alkyl groups to cellular macromolecules by forming
covalent bonds. The position 7 of guanine residues in DNA is highly susceptible because it is highly nucleophilic.
 This results in cross linking / abnormal base pairing / scission of DNA strand.
 Crosslinking of nucleic acids can also take place.
 In case of Meclorethamine (mustine), Aziridinium is the intermediate formed.
 In case of Cyclophosphamide, Phosphoramide & Acrolein are the intermediates formed.

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 Phosphoramide is the active metabolite; While Acrolein is toxic to the Urinary bladder.
 (Mercapto sulphonic acid is given to avoid damage of urinary bladder due to Acrolein)
 Ifosfamide is the congener of Cyclophosphamide.
 Thiotepa produces Aziridinium as an intermediate.
 Alkyl sulfonates undergo a process known as “Sulphur Stripping” to react with cellular macromolecules & is used in Myeloid Leukemia.
 Carmustine & Lomustine crosses B.B.B. and hence used in treatment of Brain Tumors

ANTIMETABOLITES: - These compounds prevent biosynthesis or utilization of normal cellular macromolecules.

FOLATE ANTAGONISTS: -
 Methotrexate (Amethopterine) / Aminopterine act by inhibiting dihydrofolate reductase (DHFR), which is essential for the conversion of
Dihydrofolic acid to Tetrahydrofolic acid, & step which has to occur if synthesis of folate co-enzymes has to proceed.
 Thus, they inhibit the synthesis of thymidilic acid, which is a component of the DNA.
 Administration of Folinic acid counteracts toxicity of Methotrexate.
 Methotrexate acts on S phase of the cell division.

PURINE ANTAGONISTS: -
 6-mercaptopurine, 6-thioguanine are converted to monoribonucleotide by Hypoxanthine guanine phosphoribosyl transferase (HGPRT).
 Tumor cells lack the enzyme HGPRT develop resistance to the above drugs.Monoribonucleotides inhibit the conversion of 5-
Phosphoribosylpyrophosphate to 5-phosphoribosylamine, which is required for the synthesis of purines.

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PYRIMIDINE ANTAGONISTS: -
 5-fluorouracil is converted in the body to the corresponding nucleotide.
 5-fluro-2-deoxyuridine monophosphate, which inhibits thymidilate synthetase & blocks the conversion of deoxyuridilic acid to deoxy
thymidilic acid. Thus, it inhibits the synthesis of DNA.
 Fluorouracil itself gets incorporated in to nucleic acids and this may contribute to its toxicity.

Cytarabine: -
 It is phosphorylated in the body to the corresponding nucleotide, which inhibits DNA synthesis.
 The triphosphate of cytarabine is an inhibitor of DNA polymerase & blocks the generation of cytidilic acid.

Vinca alkaloids: -
 These are mitotic inhibitors that bind to the micro tubular protein “tubulin”, prevent its polymerization & assembly of microtubules &
thus cause disruption of mitotic spindle &interfere with cytoskeletal function.
 Therefore the chromosomes fail to move apart during mitosis.
 They are cell cycle specific and they act in metaphase phase. E.g.: vincristine & vinblastine

Taxanes: -
 Paclitaxel enhances polymerization of tubulin. As a result, the microtubules are stabilized & their depolymerisation is prevented.
 This stability results IU inhibition of normal dynamic reorganization of the microtubule network that is essential for vital interphase &
mitotic functions. Abnormal arrays or bundles of microtubules are produced throughout the cell cycle.
 The major adverse effects seen are “stocking & glove” neuropathy.
 Epipodophyllotoxins such as etoposide arrest cells in the G2 Phase & causes DNA breaks by stimulating DNA topoisomerase-2

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DRUG MECHANISM OF ACTION

Actinomycin D ( Dactinomycin ) It inhibits DNA topoisomerase-2 & also interrelates in DNA, causing DNA breaks

Daunorubicin(Rubidomycin),Doxorubicin It inhibits DNA topoisomerase-2& generates quinone type free radicals.

Mitomycin It is converted in the body to act as an alkylating agent.

It blocks the conversion of ribonucleotides to deoxy ribonucleotides by inhibiting the

Hydroxyurea
enzyme ribonucleoside diphosphate reductase & thus interferes with DNA synthesis.

After metabolic activation, it depolymerises DNA & causes chromosomal damage.

Procarbazine
Inhibition of DNA synthesis occurs.

The enzyme L-Asparginase degrades l-asparginase to L- aspartic acid, depriving leukemic

L-asparginase
cells of an essential metabolite & this may cause cell death.

A platinum co-ordination complex is hydrolysed intracellularly to produce a highly reactive

Cisplatin
moiety that causes cross-linking of DNA.

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DIAGNOSTIC TESTS OF DISEASES:-

Diseases Test Deficiency disorder Drug given

1.Diptheria Shick test 1.Hypocalcaemia Calcium gluconate i.v.
2.Haemophilus Ducrey test 2.Addisons disease Corticosteroid
3.Leprosy Lepromin test 3.Anaemia Ferrous sulphate
4.Scarlet fever Dick test
5.Syphilus VDRL & Widal test
6.Tuberculosis Tuberculin test
7.Typhoid Widal test

Toxicity Drugs
1.Paracetamol, Chloroform Acetyl cysteine
2.Copper,Gold Penicillamine
3.Arsenic Dimercaprol
4.Lead Calcium EDTA
5.Iron Desferroxamine
6.Benzodiazepines Flumenazil
7.CO,CO2 Oxygen
8.Caffeine, Theophylline Esmolol

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PHARM AROCKS
GPAT STUDY M ATERIAL

ANTIBIOTICS & CHEM OTHERAPY

PHARM ACOLOGY

PHARM AROCKS GPAT SUCCESS TEST SERIES

ORGANISE BY M R. AM AR RAVAL
PHARM AROCKS GPAT SUCCESS TEST SERIES-2016: THE W AY OF SUCCESS IM P STUDY M ATERIAL

ANTIBIOTICS BY CLASS

GENERIC NAME BRAND NAMES COMMON USE POSSIBLE SIDE EFFECT MECHANISM OF ACTION
AMINOGLYCOSIDES
Amikacin Amikin Infections caused by Hearing loss Binding to the
Gentamicin Garamycin Gram-negative bacteria, such as Vertigo bacterial 30S ribosomal subuni
Kanamycin Kantrex Escherichia coli and Klebsiella Kidney damage t (some work by binding to
Neomycin Neo-Fradin particularly Pseudomonas the 50S subunit), inhibiting the
Netilmicin Netromycin aeruginosa. translocation of the peptidyl-
Tobramycin Nebcin Effective against Aerobic bacteria tRNA from the A-site to the P-
Paromomycin Humatin (not obligate/ facultative anaerobes) site and also causing
andtularemia. misreading of mRNA, leaving
the bacterium unable to
synthesize proteins vital to its
growth.
ANSAMYCINS
Geldanamycin Experimental,
Herbimycin As antitumor antibiotics
CARBACEPHEM
Loracarbef Lorabid Discontinued Prevents bacterial cell division by
inhibiting cell wall synthesis.

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CARBAPENEMS
Ertapenem Invanz Bactericidal for both Gastrointestinal upset and Inhibition of cell wall
Doripenem Doribax Gram-positive and Gram-negative diarrhea synthesis
Imipenem Cilastatin Primaxin organisms and therefore useful for Nausea
Meropenem Merrem empiric broad-spectrum antibacterial Seizures
coverage. (Note MRSA resistance to Headache
this class.) Rash and allergic reactions
CEPHALOSPORINS (FIRST GENERATION)
Cefadroxil Duricef Good coverage against Gastrointestinal upset Same mode of action as
Cefazolin Ancef Gram positive infections. and diarrhea other beta-lactam antibiotics:
(discontinued) Nausea disrupt the synthesis of
Cefalotin or Cefal Keflin (if alcohol taken thepeptidoglycan layer of
othin (discontinued) concurrently) bacterial cell walls.
Cefalexin Keflex Allergic reactions
CEPHALOSPORINS (SECOND GENERATION)
Cefaclor Distaclor Less gram positive cover, improved Gastrointestinal upset and Same mode of action as
Cefamandole Mandol gram negative cover. diarrhea, Nausea other beta-lactam antibiotics:
(discontinued) (if alcohol taken disrupt the synthesis of
Cefoxitin Mefoxin concurrently) thepeptidoglycan layer of
(discontinued) Allergic reactions bacterial cell walls.

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Cefprozil Cefzil
Cefuroxime Ceftin, Zinnat
(UK)
CEPHALOSPORINS (THIRD GENERATION)
Cefixime Suprax Improved coverage of Gastrointestinal upset and Same mode of action as
Cefdinir Omnicef, Gram negative organisms, except diarrhea Nausea other beta-lactam antibiotics:
Cefdiel Pseudomonas. Reduced Gram (if alcohol taken Disrupt the synthesis of
Cefditoren Spectracef positive cover. concurrently) thepeptidoglycan layer of
Cefoperazone Cefobid Allergic reactions bacterial cell walls.
(discontinued)
Cefotaxime Claforan
Cefpodoxime Vantin
Ceftazidime Fortaz
Ceftibuten Cedax
Ceftizoxime Cefizox
(discontinued)
Ceftriaxone Rocephin

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CEPHALOSPORINS (FOURTH GENERATION)

Cefepime Maxipime Covers pseudomonal infections. Gastrointestinal upset Same mode of action as
and diarrhea other beta-lactam antibiotics:
Nausea (if alcohol taken disrupt the synthesis of
concurrently) thepeptidoglycan layer of
Allergic reactions bacterial cell walls.
CEPHALOSPORINS (FIFTH GENERATION)
Ceftaroline Teflaro Used to treat MRSA Gastrointestinal upset Same mode of action as
fosamil and diarrhea other beta-lactam antibiotics:
Allergic reaction Disrupt the synthesis of
thepeptidoglycan layer of
bacterial cell walls.
Ceftobiprole Zeftera Used to treat MRSA Gastrointestinal upset Same mode of action as
and diarrhea other beta-lactam antibiotics:
Nausea (if alcohol taken Disrupt the synthesis of
concurrently) thepeptidoglycan layer of
Allergic reactions bacterial cell walls.

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GLYCOPEPTIDES
Teicoplanin Targocid (UK) Active agaist aerobic and anaerobic Inhibiting peptidoglycan
Vancomycin Vancocin Gram positive bacteria including synthesis
Telavancin Vibativ MRSA;
Vancomycin is used orally for the
treatment of C. difficile
LINCOSAMIDES
Clindamycin Cleocin Serious staph-, pneumo-, and Possible C. difficile- Bind to 50S subunit of
Lincomycin Lincocin streptococcal infections in penicillin- related pseudomembranous bacterial
allergic patients, also anaerobic enterocolitis ribosomal RNAthereby
infections; clindamycin topically inhibiting protein synthesis
for acne
LIPOPEPTIDE
Daptomycin Cubicin Gram-positive organisms Bind to the membrane and
cause rapid depolarization,
resulting in a loss of
membrane potential leading to
inhibition of protein, DNA and
RNA synthesis

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MACROLIDES
Azithromycin Zithromax, Streptococcal infections, Nausea, Inhibition of bacterial protein
Sumamed, syphilis, vomiting biosynthesis by binding
Xithrone upper respiratory tract infections, diarrhea reversibly to the
Clarithromycin Biaxin lower respiratory tract infections, (especially at high doses) subunit 50S of the
Dirithromycin Dynabac mycoplasmal infections, bacterial ribosome,
(discontinued) Lyme disease Prolonged QT interval There by inhibiting
Erythromycin Erythocin,Erythr (especially erythromycin) translocation of
oped Jaundice peptidyl tRNA.
Roxithromycin
Troleandomycin Tao
(discontinued)
Telithromycin Ketek Pneumonia Visual Disturbance,
Liver Toxicity.[4]
Spectinomycin Trobicin Gonorrhea
Spiramycin Rovamycine Mouth infections

MONOBACTAMS

Aztreonam Azactam Same mode of action as other beta-

lactam antibiotics:
Disrupt the synthesis of

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thepeptidoglycan layer of
bacterial cell walls.
Nitrofurans
Furazolidone Furoxone Bacterial
or protozoal diarrhea orenteritis
Nitrofurantoin Macrodantin, Urinary tract infections
Macrobid
PENICILLINS
Amoxicillin Novamox, Wide range of infections; penicillin Gastrointestinal upset Same mode of action as
Amoxil used for streptococcal infections, and diarrhea other beta-lactam antibiotics:
Ampicillin Principen syphilis, Allergy with Disrupt the synthesis of
(discontinued) Lyme disease seriousanaphylactic thepeptidoglycan layer of
Azlocillin reactions bacterial cell walls.
Carbenicillin Geocillin Brain and kidney damage
(discontinued) (rare)
Cloxacillin Tegopen
(discontinued)
Dicloxacillin Dynapen
(discontinued)
Flucloxacillin Floxapen(Sold to
European

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generics Actavis
Group)
Mezlocillin Mezlin
(discontinued)
Methicillin Staphcillin
(discontinued)
Nafcillin Unipen
(discontinued)
Oxacillin Prostaphlin
(discontinued)
Penicillin G Pentids
(discontinued)
Penicillin V Veetids
(Pen-Vee-K)
(discontinued)
Piperacillin Pipracil
(discontinued)
Penicillin G Pfizerpen
Temocillin Negaban (UK)
(discontinued)

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Ticarcillin Ticar
(discontinued)
PENICILLIN COMBINATIONS
Amoxicillin Augmentin The second component
clavulanate prevents bacterialresistance to
Ampicillin Unasyn the first component
sulbactam
Piperacillin Zosyn
tazobactam
Ticarcillin Timentin
clavulanate
POLYPEPTIDES
Bacitracin Eye, ear or bladder infections; Kidney and nerve Inhibits isoprenyl
usually applied directly to the eye or damage (when given by pyrophosphate,
inhaled into the lungs; rarely given injection) a molecule that carries the
by injection, although the use of building blocks of
intravenous colistin is experiencing a the peptidoglycanbacterial
resurgence due to the emergence cell wall outside of the inner
of multi drug resistant organisms. membrane
Colistin Coly-Mycin-S Interact with the gram

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Polymyxin B negative bacterial outer

membrane and cytoplasmic
membrane.
It displaces bacterial counter
ions, which destabilizes the
outer membrane.
They act like a detergent
against the cytoplasmic
membrane, which alters its
permeability.
Polymyxin B and E are
bactericidal even in an
isosmotic solution.
QUINOLONES
Ciprofloxacin Cipro,Ciproxin, Urinary tract infections, Nausea (rare), Inhibit the bacterial DNA
Ciprobay bacterial prostatitis, irreversible damage gyrase or thetopoisomerase IV
Enoxacin Penetrex community-acquiredpneumonia, to central nervous enzyme,
Gatifloxacin Tequin bacterial diarrhea, system(uncommon), There by inhibiting DNA
Levofloxacin Levaquin mycoplasmal infections, tendinosis (rare) replication and transcription.
Lomefloxacin Maxaquin gonorrhea

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Moxifloxacin Avelox
Nalidixic acid NegGram
Norfloxacin Noroxin
Ofloxacin Floxin, Ocuflox
Trovafloxacin Trovan Withdrawn
Grepafloxacin Raxar Withdrawn
Sparfloxacin Zagam Withdrawn
Temafloxacin Omniflox Withdrawn
SULFONAMIDES
Mafenide Sulfamylon Urinary tract infections Nausea, vomiting, and Folate synthesis inhibition.
Sulfonamidochrys Prontosil (except sulfacetamide, used for eye diarrhea They are competitive
oidine(archaic) infections, and mafenide and silver Allergy(including skin inhibitors of the
Sulfacetamide Sulamyd, Bleph- sulfadiazine, used topically forburns) rashes) enzyme dihydropteroate
10 Crystals in urine synthetase,
Sulfadiazine Micro-Sulfon Kidney failure DHPS. DHPS catalyses the
Silver sulfadiazine Silvadene Decrease inwhite blood conversion of PABA
Sulfamethizole Thiosulfil Forte cellcount (para-aminobenzoate)
Sulfamethoxazole Gantanol Sensitivity to sunlight to dihydropteroate, a key step

Sulfanilimide (arc in folate synthesis. Folate is

haic) necessary for the cell to

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Sulfasalazine Azulfidine synthesize nucleic

Sulfisoxazole Gantrisin acids (nucleic acids are
Trimethoprim- Bactrim, Septra essential building blocks
Sulfamethoxazole of DNA andRNA), and in its
(Co-trimoxazole) absence cells will be unable to
(TMP-SMX) divide.
TETRACYCLINES
Demeclocycline Declomycin Syphilis, Gastrointestinal upset Inhibiting the binding
Doxycycline Vibramycin chlamydial infections, Sensitivity to sunlight of aminoacyl-tRNA to them
Minocycline Minocin Lyme disease, Potential toxicity to mother RNA-ribosome complex.
Oxytetracycline Terramycin Mycoplasmal infections, and fetus during pregnancy
Tetracycline Sumycin,Achro Acne rickettsialinfections, Enamel hypoplasia They do so mainly by binding
mycin V,Steclin * malaria (staining of teeth; potentially to the 30S ribosomal
* Note: Malaria is caused by permanent) subunit in the mRNA
a protist and not a bacterium. transient depression of bone translation complex.
growth

DRUGS AGAINST MYCOBACTERIA

Clofazimine Lamprene Antileprotic
Dapsone Avlosulfon Antileprotic

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Capreomycin Capastat Antituberculosis

Cycloserine Seromycin Antituberculosis, urinary tract
infections
Ethambutol Myambutol Antituberculosis
Ethionamide Trecator Antituberculosis Inhibits peptide synthesis

Isoniazid I.N.H. Antituberculosis

Pyrazinamide Aldinamide Antituberculosis
Rifampicin Rifadin, mostly Gram- Reddish-orange sweat, tears, Binds to the β subunit of RNA
(Rifampin in US) Rimactane positive andmycobacteria and urine polymerase to inhibit
transcription
Rifabutin Mycobutin Mycobacterium avium complex rash, discolored urine,
GI symptoms
Rifapentine Priftin Antituberculosis
Streptomycin Antituberculosis Neurotoxicity,ototoxicity As other aminoglycosides

OTHERS
Arsphenamine Salvarsan Spirochaetal infections (obsolete)
Chloramphenicol Chloromycetin Meningitis, MRSA, topical use, or Rarely: Inhibits bacterial protein
for low cost internal treatment. aplastic anemia. synthesis by binding to the
Historic: typhus, cholera. gram 50S subunit of the ribosome
negative, gram positive, anaerobes

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Fosfomycin Monurol Acute cystitis in women Inactivates enolpyruvyl

transferase, thereby
blocking cell wall synthesis
Fusidic acid Fucidin
Linezolid Zyvox VRSA Thrombocytopenia

Metronidazole Flagyl Infections caused by anaerobic Discolored urine,headache, Produces toxic free
bacteria; metallic taste, radicals which disrupt DNA
also amoebiasis, nausea ; and proteins.
trichomoniasis, alcohol is contraindicated This non-specific mechanism
Giardiasis is responsible for its activity
against a variety of bacteria,
Amoebae, and protozoa.
Mupirocin Bactroban Ointment for impetigo, cream for Inhibits isoleucine t-RNA
infected cuts synthetase (IleRS) causing
inhibition of protein synthesis
Platensimycin
Quinupristin/Dalf Synercid
opristin
Rifaximin Xifaxan Traveler's diarrhea caused by
E. coli

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Thiamphenicol Gram-negative, Gram-positive, Lacks known anemic side- A chloramphenicol analog.

anaerobes. Widely used in veterinary effects. May inhibit bacterial protein
medicine. synthesis by binding to the
50S subunit of the ribosome
Tigecycline Tigacyl
Tinidazole Tindamax protozoan infections upset stomach, bitter taste,
Fasigyn and itchiness
Trimethoprim Proloprim, Urinary Tract Infections
Trimpex

 HI FRIENDS HERE ALL THE DRUGS ARE COVER FROM ANTIBIOTIC SECTION OF PHARMACOLOGY
 MUST PREPARE THIS ALL TABLES
 THEY HELS DURING YOUR GPAT EXAM AS WELL AS IN THE FINAL YEAR OF B.PHARM
 PREPARE WELL ABOUT DRUG AND THEIR SIDE EFFECTS AND MOA.
 ALL THE BEST
 KEEP ROCKING WITH PHARMAROCKS

AMAR M. RAVAL
OWNER: PHARMAROCKS

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PHARM AROCKS GPAT SUCCESS TEST SERIES-2016 SOLID DOSAGE FORM TABLETS

SOLID DOSAGE FORMS  TABLETS

Syllabus:
Types of tablets
Tablet ingredients: Diluents, binders, disintegrating agents, lubricants, colorants, flavoring and sweeteners.
Principles, materials and equipment involved in drying and mixing of powders, granulation and compression
of tablets.
Layout of a tableting section. Principles of refrigeration-air conditioning, humidification and dehumidification
and fluidization as applied to the manufacturing of tablets.
Principles, processes, materials and equipment involved in coating of dosage forms with sugar, enteric coating
materials and film-formers.
Quality control and standards of coated dosage forms.

Questions:
1. Short note on tablet coatings.
2. Explain the advantages of tablet dosage forms
3. Describe the different methods of preparation of tablets
4. Write a brief note on tablet additives with examples
5. Discuss the different classes of pharmaceutical excipients that go into tablet formulation giving examples
to each class.
6. Draw a sketch of the layout of a tablet manufacturing unit.
7. Differentiate between capsule unit and this. Short note on proper drying of granules.
8. Write an account on the phenomena, processing and importance of enteric coating.
9. Discuss the details of manufacturing of ascorbic acid tablets, explaining each step in the manufacture.

DEFINITION
Tablets may be defined as solid pharmaceutical dosage forms containing drug substances with or
without suitable diluents and prepared either by compression or moulding methods.
This dosage form is intended to be administered through oral route.
Definition according to Indian Pharmacopoeia
“Pharmaceutical tablets are flat or bi-convex discs prepared by compressing a drug or a mixture of
drugs with or without suitable diluents.”
Advantages of tablet dosage form over other oral drug delivery systems:
From patients stand point?
1. They are easy to carry.
2. They are easy to swallow.
3. They are attractive in appearance.
4. Unpleasant taste can be masked by sugar coating.
5. They do not require any measurement of dose. The strip or blister packing has further facilitated
the process of taking the dose by the patient. Moreover, it provides a sealed covering which
protects the tablets from atmospheric conditions like air, moisture and light etc.
6. Some of the tablets are divided into halves and quarters by drawing lines during manufacturing to
facilitate breakage whenever a fractional dose is required.
From the standpoint of manufacturer:
7. An accurate amount of medicament, even if very small, can be incorporated.
8. Tablets provide prolonged stability to medicament. They have the best combined properties of
chemical, mechanical and microbiological stability of all the oral dosage forms.
9. The incompatibilities of medicaments and their deterioration due to environmental factors are less
in tablet forms.
10. Since they are generally produced on a large scale, therefore, their cost of production is relatively
low, hence economical.
11. They are in general the easiest and cheapest to package and ship among all oral dosage forms.

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12. Some specialized tablets like enteric coated tablet, sustained release tablets may be prepared for
modified release profile of the drug.
13. Product identification is potentially the simplest and cheapest requiring no additional processing
steps when employing an embossed or monogrammed punch face.
Disadvantages of tablet dosage forms:
(i) Some drugs resist compression into dense compacts, owing to their amorphous nature or flocculent,
low-density character.
(ii) Drugs with poor wetting, slow dissolution properties, intermediate to large dose, or any
combination of these features may be difficult or impossible to formulate and manufacture as a
tablet that will still provide adequate bioavailability.
(iii) Bitter tasting drugs, drugs with objectionable odour, or drugs sensitive to oxygen or atmospheric
moisture may require encapsulation or entrapment prior to compression (if feasible of practical) or
the tablets may require coating.

TYPES OF TABLETS
Tablets are classified according to their route of administration or function. The following are the four
main classification groups:

(A) Tablets ingested orally: (C) Tablets administered by other routes:

(i) Compressed tablets (i) Implantation tablets
(ii) Multiple compressed tablets (ii) Vaginal tablets
(iii) Enteric coated tablets (D) Tablets used to prepare solutions:
(iv) Sugar coated tablets (i) Effervescent tablets
(v) Film coated tablets (ii) Dispensing tablets
(vi) Chewable tablets (iii) Hypodermic tablets
(B) Tablets used in the oral cavities: (iv) Tablet triturates
(i) Buccal cavities
(ii) Sublingual tablets
(iii) Lozenges
(iv) Dental cone

(A) TABLETS INGESTED ORALLY

These tablets are designed to be swallowed except the chewable tablets. The tablets covered in this
category are:
Compressed tablets (C.T.)
These tablets are formed by compression and contain no special coating. They are made from
powdered, crystalline or granular materials, alone or in combination with diluent, binders, disintegrants,
lubricants, antiadherants and in many cases colorants.
These tablets contain water soluble drugs which after swallowing get disintegrated in the stomach and
its drug contents are absorbed in the gastrointestinal tract and distributed in the whole body. E.g.
Aspirin (, Dispirin) paracetamol tablets (Crocin)
Multiple compressed tablets:
These are compressed tablets made by more than one compression cycle:
Layered tablets
Such tablets are prepared by compressing additional tablet granulation on a previously compressed
granulation. The operation may be repeated to produce multilayered tablets of two or three layers.
Special tablet presses are required to make layered tablets such as Versa press. (Stokes/Pennwalt)
These tablets are prepared to separate physically or chemically incompatible ingredients or to produce
repeat action or prolonged action products.
To avoid incompatibility, the ingredients of the formulation except the incompatible material are
compressed into a tablet and then incompatible substance along with necessary excipients are
compressed over the previously compressed tablet.

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Sustained action tablets:

These are the tablets which after oral administration release the drug at a desired time and prolong the
effect of the medicament. These tablets when taken orally release the medicament in a sufficient
quantity as and when required to maintain the maximum effective concentration of the drug in the blood
throughout the period of treatment.
E.g. Diclofenac SR tablets.
Enteric coated tablets:
These are compressed tablet meant for administration by swallowing and are designed to by-pass the
stomach and get disintegrated in the intestine only.
These tablets are coated with materials resistant to acidic pH (like cellulose acetate phthalate, CAP) of
the gastric fluid but get disintegrated in the alkaline pH of the intestine. These tablets are made to
release the drug undiluted and in the highest concentration possible within the intestine, e.g. tablets
containing anthelmintic and amoebicides.
Sugar coated tablets:
These are compressed tablets containing a sugar coating. Such coatings are done to mask the bitter and
unpleasant odour and the taste of the medicament. The sugar coating makes the tablet elegant and it
also safeguard the drug from atmospheric effects.
Film coated tablets:
The compressed tablets having a film coating of some polymer substance, such as hydroxy propyl
cellulose, hydroxy propyl methyl cellulose and ethyl cellulose. The film coating protects the
medicament from atmospheric effects. Film coated tablets are generally tasteless, having little increase
in the tablet weight and have less elegance than that of sugar coated tablets.
Chewable tablets:
These are the tablets which are required to be broken and chewed in between the teeth before ingestion.
These tablets are given to the children who have difficulty in swallowing and to the adults who dislike
swallowing.
A number of antacid tablets and multivitamin tablets are prepared as chewable tablets.
For the preparation of chewable tablets mannitol is used as a sweetening base. Since mannitol is
expensive other substances like sorbitol, lactose, chocolate powder, dextrose and glycerin can be
substituted in place of mannitol. These tablets do not require any disintegrating agents to be present in
the formulation.
These tablets should have very acceptable taste and flavour.
E.g. antacid tablets
Vitamin C chewable tablets e.g. CELIN - (Glaxo)

(B) TABLETS USED IN ORAL CAVITY

Buccal tablets:
These tablets are to be placed in the side of the cheek (buccal pouch) where they dissolve or erode
slowly and are absorbed directly in the buccal cavity without passing into the alimentary canal.
Therefore, they are formulated and compressed with sufficient pressure to give a hard tablet e.g.
Progesterone tablets.
Sublingual tablets:
These tablets are to be placed under the tongue where they dissolve or disintegrate quickly and are
absorbed directly without passing into GIT e.g. tablets of nitroglycerin, isoproterenol hydrochloride or
erythrityl tetranitrate.
Lozenges tablets:
These tablets are designed to exert a local effect in the mouth or throat. These tablets are commonly
used to treat sore throat to control coughing in common cold. They may contain local anaesthetics,
antiseptics, antibacterial agents, astringents and antitussives.
These are prepared by compression at a high pressure by the moulding process and generally contain a
sweetening agent, flavouring agent (e.g. peppermint, clove oil) and a substance which produces a
cooling effect (e.g. mentha). E.g. Vicks lozenges.

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Dental cones:
These are compressed tablets meant for placement in the empty sockets after tooth extraction. They
prevent the multiplication of bacteria in the socket following such extraction by using slow-releasing
antibacterial compounds or to reduce bleeding by containing the astringent.
These tablets contain an excipient like lactose, sodium bicarbonate and sodium chloride.
These cones generally get dissolved in 20 to 40 minutes time.

(C) TABLETS ADMINISTERED BY OTHER ROUTES

Implantation tablets:
These tablets are placed under the skin or inserted subcutaneously by means of minor surgical
operation and are slowly absorbed. These may be made by heavy compression but are normally made
by fusion. The implants must be sterile and should be packed individually in sterile condition. Implants
are mainly used for the administration of hormones such as testosterone steroids for contraception.
These tablets are very usefully exploited for birth control purpose in human beings.
The disadvantages of implant tablets are their administration changing rate of release with change of
surface area and possibility of tissue reactions.
Vaginal tablets:
These tablets are meant to dissolve slowly in the vaginal cavity. The tablets are typically ovoid or pear
shaped for the ease of insertion. These tablets are used to release steroids or antimicrobial agents. The
tablets are often buffered to promote a pH favorable to the action of a specified antimicrobial agent.
The contains easily soluble components like lactose or sodium bicarbonate.

(D) TABLETS USED TO PREPARE SOLUTIONS

Effervescent tablets:
These tablets along with the active medicament contain ingredients like sodium bicarbonate, citric acid
and tartaric acid which react in the presence of water liberating carbon dioxide and producing
effervescence leading to disintegration of the tablet, thus hastens solution formation and increase the
palatability.
Dispensing tablets:
These tablets provide a convenient quantity of potent drug that can be incorporated readily into
powders and liquids, thus circumventing the necessity to weigh small quantities. These tablets are
supplied primarily as a convenience for extemporaneous compounding and should never be dispensed
as dosage form.
E.g. the drugs commonly incorporated are mild silver potentiate, bichloride of mercury merbromin a
quarternary ammonium compounds.
Hypodermic tablets:
Hypodermic tablets are soft, readily soluble tablets and originally were used for the preparation of
solutions to be injected. These tablets are dissolved in sterile water or water for injection and
administered by parenteral route. These tablets are not preferred now-a-days because the resulting
solution is not always sterile.
Tablet triturates (Moulded tablets):
These are powders moulded into tablets. They are flat, circular discs, usually containing a potent
substance mixed with lactose, lactose and sucrose, dextrose, or other suitable diluent.
Since they are intended to disintegrate very quickly in contact with moisture, water insoluble adjuncts
are avoided. The name ‘tablet triturate’ is appropriate because they usually contain triturations
(trituration = dilution with an inert substance).

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TABLET INGREDIENTS
In addition to the active or therapeutic ingredient(s), tablets contain a number of inert materials. The
latter are known as additives or excipients.
They may be classified according to the part they play in the finished tablet.
Group-I: Contains those which help to impart satisfactory processing and compression
characteristics to the formulation. This includes: diluents, binders, glidants and
lubricants.
Group-II: Helps to give additional desirable physical characteristics to the finished tablet. This
includes: disintegrants, colours, and in the case of chewable tablets, flavors and
sweetening agents.
Group-III: In the case of controlled-release tablets, polymers or waxes or other solubility-
retarding materials.

DILUENTS
Objectives of incorporating diluents:
(i) Frequently, the single dose of the active ingredient is small and an inert substance is added to
increase the bulk in order to make the tablet a practical size for compression.
Compressed tablets of dexamethasone contains 0.75 mg steroid per tablet; hence, it is obvious that
another material must be added to make tableting possible.
The dose of some drugs is sufficiently high that no filler is required (e.g. aspirin and certain
antibiotics).
Diluents used for this purpose include dicalcium phosphate (DCP), calcium sulfate, lactose, cellulose,
kaolin, mannitol, dry starch and powdered sugar.
(ii) Certain diluents, such as mannitol, lactose, sorbitol, sucrose and inositol, when present in
sufficient quantity, can impart properties that will help in disintegration of the tablet in the mouth
by chewing. Such tablets are commonly called chewable tablets.
(iii) Diluents used for direct compression formulas give the powder mixture necessary flowability and
compressibility.
(iv) To delay or control the rate of release of drug from the tablet.

Characteristics of an ideal diluents:

1. They must be nontoxic and acceptable to the regulatory agencies in all countries where the product
is to be marketed.
2. They must be commercially available in an acceptable grade in all countries where the product is to
be manufactured.
3. They must be cheap compared to the active ingredients.
4. They must be physiologically inert.
5. They must be chemically stable alone and/or in combination with the drug(s) and/or other tablet
components.
6. They must be free of any unacceptable “microbiological load”.
7. They must be color-compatible (should not produce any off-color appearance).
8. They must have no negative effects on the bioavailability of the drug(s) in the product.
[N.B. e.g. Calcium phosphate as diluent, reduces the bioavailability of some antibiotics like tetracycline.]

Classification of diluents:
DILUENTS
Sugars Polysaccharides Inorganic compounds Miscellaneous compounds
Dextrose Starches Calcium phosphate dihydrate Bentonite
Lactose Modified starch Calcium sulfate dihydrate Polyvinyl pyrrolidone
Sucrose E.g. Sta-RX 1500, Celutab etc. Calcium lactate trihydrate Kaolin
Amylose Cellulose Calcium carbonate Silicone derivatives
Mannitol Cellulose derivatives Magnesium carbonate
Sorbitol Microcrystalline cellulose Magnesium oxide
Inositol (MCC)

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CALCIUM SALTS
Example: Dibasic calcium phosphate dihydrate (or dicalcium orthophosphate) (DCP) [CaHPO4,
2 H2O], Calcium sulfate dihydrate (CaSO4, 2H2O).
Advantages:
 Diluents that exist in their common salt form as hydrates, containing appreciable bound water as
water of crystallization. This bound water of calcium sulfate is not released below 800C. They
possess very low concentration of unbound moisture. Hence, these salts are excellent diluents for
water-sensitive drugs. It is superior to anhydrous diluent, which has a moderate to high moisture
demand.
Disadvantages:
 Tetracycline products made with calcium phosphate diluent had less than half the bioavailability of
the standard product. Divalent cation (Ca++) form insoluble complexes and salts with number of
amphoteric or acidic functionality antibiotics, which generally reduces their absorption (which is
also why milk should not be co-administered with these drug).

LACTOSE
Lactose is the most widely used diluent for tablet formulation.
 It is obtained in hydrous and anhydrous form. The anhydrous form, picks up moisture when
exposed to elevated humidity. Such tablets should be packed in moisture proof packets or
containers. When a wet granulation method is employed, the hydrous form of lactose should
generally be used.
 Two grades of lactoses are commercially available:
(i) A 60 to 80 mesh – coarse
(ii) A 80 to 100 mesh – regular grade
Advantages:
1. Lactose has no reaction with most of the drugs, whether in hydrous or anhydrous form.
2. Lactose formulations show good release rates
3. Their granulations are readily dried, and the tablet disintegration times of lactose tablets are not
strongly sensitive to variations in tablet hardness.
4. It is a low cost diluent.
Disadvantages:
1. Lactose reacts with amine drug bases in presence of alkaline lubricants e.g. metal stearates (e.g.
magnesium stearate) and gradually discolours (dark brown) with time due to the formation of
furaldehyde. This reaction is called Maillard reaction.

SPRAY DRIED LACTOSE

Advantages:
1. It is used for direct compression (containing drug + diluent + disintegrant + lubricant)
2. In addition to the direct compression properties, spray dried lactose also has good flow
characteristics. It can usually be combined with as much as 20 to 25% of active ingredients without
losing these advantageous features.
Disadvantages:
1. If spray dried lactose is allowed to dry out and the moisture content falls below the usual 3% level,
the material loses some of its direct compressional characteristics.
2. Spray-dried lactose is especially prone to darkening in the presence of excess moisture, amines, and
other compounds owing to Maillard reactions. Hence, a neutral or acid lubricant should be used.

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STARCH
Starch may be obtained from corn, wheat or potatoes. It is occasionally used as a tablet diluent
 USP grade of starch is usually possesses moisture content between 11 to 14%.
 Specially dried types of starch that have a standard moisture level of 2-4% are available, but are
costly. Use of such starches in wet granulation is wasteful since their moisture level increase to 6-
8% following moisture exposure.
DIRECTLY COMPRESSIBLE STARCHES
Sta–Rx 1500 – free flowing, directly compressible starch
– used as diluent, binder, disintegrant
Emdex and Celutab – are two hydrolyzed starches
– contains dextrose 90–92%
Maltose 3–5%
– free flowing and directly compressible
– may be used in place or mannitol in chewable tablets because of their
sweetness and smooth feeling in the mouth.
DEXTROSE (D–Glucose)
Available in two forms: as hydrates and anhydrous forms.
Dextrose may sometimes be combined in formulation to replace some of the spray-dried lactose, which
may reduce the tendency of the resulting tablets to darken.

MANNITOL
Advantages
 Because of the negative heat of solution (cooling sensation in the mouth) its slow solubility, and its
pleasant feeling in the mouth, it is widely used in chewable tablets.
 It is relatively non-hygroscopic and can be used in vitamin formulations.
 Low calorie content and non-carcinogenic.
Disadvantages
 Costly
 Mannitol has poor flow characteristics and usually require fairly high lubricant level.

SORBITOL
It is an optical isomer of mannitol and is sometimes combined with mannitol formulations to
reduce the diluent cost.
Disadvantages: It is hygroscopic at humidities above 65%.

SUCROSE
Some sucrose based diluents are:
Sugar tab – 90 to 93% sucrose + 7 to 10% invert sugar
Di Pac – 97% sucrose + 3% modified dextrins
Nu Tab – 95% sucrose + 4% invert sugar + small amount of corn starch + Mg-stearate
Advantages: They are all used for direct compression.
Disadvantages: All are hygroscopic when exposed to elevated humidity.

MICROCRYSTALLINE CELLULOSE (MCC)

Trade Name: Avicel – is a directly compression material
Two grades are available PH 101  powder
PH 102  granules
Advantages: It acts as diluent and disintegrating agents.

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BINDERS
Agents used to impart cohesive qualities to the powdered material are referred to as binders or
granulators.
Objective of incorporating binders
1. They impart a cohesiveness to the tablet formulation (both direct compression and wet–granulation
method) which insures the tablet remaining intact after compression.
2. They improves the free-flowing qualities by the formation of granules of desired size and hardness.

Characteristics of binder
Method-I
Binders are used in dry form in the powder and then moistened with a solvent (of the binder) to form
wet lumps.
Method-II
Binders are often added in solution form. It requires lower concentration of binder.
By Method-I the binder is not as effective in reaching and wetting each of the particles within
the mass of the powder. Each of the particle in a powder blend has a coating of adsorbed air on its
surface, and it is this film of air which must be penetrated before the powder can be wetted by the
binder solution.
Method-III
In direct compression method MCC, microcrystalline dextrose, amylose and PVP are used – those have
good flow property and cohesiveness as well.
It has been postulated that MCC is a special form of cellulose fibril in which individual
crystallites are held together largely by hydrogen bonding. The disintegration of tablets containing the
cellulose occurs by breaking intercrystallite bonds by the disintegrating medium.

STARCH PASTE
Corn starch is often used in the concentration of 10–20%.
Method of preparation
Corn starch is dispersed in cold purified water to make a 5 to 10% w/w suspension and then warming
in water both with continuous stirring until a translucent paste is formed... (Actually hydrolysis of
starch takes place.)

LIQUID GLUCOSE
50% solution in water is fairly common binding agent.

SUCROSE SOLUTION
50% to 74% sugar solution is used as binder. They produce hard but brittle granules. Their
cost is low.

GELATIN SOLUTION
Concentration 10–20% aqueous solution
Should be prepared freshly and added in warm condition other wise it will become solid.
Method of preparation
The gelatin is dispersed in cold water and allowed to stand until hydrated. The hydrated mass is
warmed in water bath to dissolve.
CELLULOSIC SOLUTIONS
HPMC (Hydroxy propyl methyl cellulose) Soluble in cold water.
Method of preparation: HPMC is dispersed in hot water, under agitation. The mixture is cooled
as quickly as possible and as low as possible
HEC (Hydroxy ethyl cellulose), HPC (Hydroxy propyl cellulose) are other successful binders.
PVP (Polyvinylpyrollidone) Used as an aqueous or alcoholic solution. Concentration 2% and may vary.

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LUBRICANTS
Objectives:
1. Prevents adhesion of the tablet material to the surface of dies and punches.
2. Reduce inter-particular friction, improve the rate of flow of tablet granulation.
3. Facilitate ejection of the tablets from the die cavity.

Examples:
Talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oils and polyethylene
glycols (PEG).

Method of addition of lubricants:

1. The lubricant is divided finely by passing it through a 60 to 100 mesh nylon cloth on to the
granulation. In production this is called ‘bolting the lubricant’.
2. After addition the granulation is tumbled or mixed gently to distribute the lubricant without coating
all the particles too well.
* Complete coating will produce dissolution problem.
* Prolonged mixing will produce excessive fines by breaking the granules.
Soluble lubricants
Examples: Sodium benzoate – includes a mixture of sodium benzoate and sodium acetate
Sodium chloride, leucine and carbowax 4000.

Magnesium stearate
Though it is a widely used lubricant it retards disintegration and dissolution. To overcome this
some time surfactants like sodium lauryl sulfate are included.

Lubricants are included to reduce the friction during tablet ejection between the walls of the tablet and
the wall of the die in which the tablet was formed.
Antiadherents are used for the purpose of reducing the sticking or adhesion of any of the tablet
ingredients or powder to the faces of the punches or to the die wall.
Glidants are intended to promote flow of the tablet granulation or powder materials by reducing the
friction between the particles.

An ingredient used for lubrication purpose may possess other two properties as well.
Relative properties of some tablet lubricants:
Material Usual Glidant Antiadherent Lubricant
percent properties properties properties
1. Calcium or Magnesium stearate 1 or less Poor Good Excellent
2. Talc 1–5 Good Excellent Poor
3. Stearic acid 1–5 None Poor Good
4. High melting waxes 3–5 None Poor Excellent
5. Corn starch 5 – 10 Excellent Excellent Poor

Water soluble tablet lubricants

Lubricant Percentage
Boric acid 1
Sodium chloride 5
Sodium benzoate 5
Sodium acetate 5
Sodium oleate 5
PEG 4000, 600 1–4
dl-leucine 1–5

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DISINTEGRANTS
Definition
A disintegrant is a substance to a mixture of substances, added to tablet to facilitate its breakup
or disintegration after administration in the GIT.
The active ingredients must be released from the tablet matrix as efficiently as possible to allow
for its rapid dissolution.
Disintegrants can be classified chemically as:
Starches, clays, celluloses, alginates, gums and cross-linked polymers.
Starch
Corn starch, potato starch
For their disintegrating effect starches are added to the powder blends in dry state.
Mode of action:
Starch has a great affinity for water and swells when moistened, thus facilitating the rupture of
the tablet matrix.
Others have suggested that the spherical shape of the starch grains increases the porosity of the
tablet, thus promoting capillary action.
Normally 5% w/w is suggested.
For rapid disintegration 10 – 15% w/w may be taken.

Super disintegrants
Croscarmelose - cross linked cellulose
Crospovidone - cross linked polyvinyl pyrrolidone
Sodium starch glycolate - cross linked starch
Mode of action
Croscarmelose swells 4 to 8 fold in less than 10 seconds
Crospovidone acts by wicking or capillary action.
Sodium starch glycolate swells 7 to 12 folds in less than 30 seconds.

Other materials
Veegum HV, Methyl cellulose, Agar, Bentonite, Cellulose, Alginic acid,
Guargum, and Carboxymethyl cellulose.
 Sodium lauryl sulfate is a surfactant. It increases the rate of wetting of the tablet, thus decreases
the disintegrating time.

Method of blending with powder

The disintegrants are usually mixed with active ingredients and diluents prior to granulation.
Starch may be divided into two portions:
One part – added prior to granulation
Remainder – added prior to compression.
While disintegration the portion of the starch added prior to compression rapidly breaks down the tablet
to granules, and the starch mixed prior to granulation disintegrates the granules into smaller particles.

COLOURING AGENT
Objectives of using colors
(i) It makes the tablet more esthetic in appearance.
(ii) Colour helps the manufacturer to identify the product during its preparation.
All colorants used in pharmaceuticals must be approved and certified by the FDA (food & Drug
Administration). Dyes are generally listed as FD&C (food, Drug & Cosmetic Dyes) dyes and D&C
(Drug & Cosmetic Dyes).

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Colour Other Names Color Index (CI, 1971)

D&C Red 22 Eosin Y 45380
FD&C Yellow 5 Tartrazine 15985
FD&C Yellow 6 Sunset Yellow FCF 19140
Yellow Orange 5
FD&C Blue 1 Brilliant Blue FCF 42090
FD&C Blue 2 Indigocarmine 73015
FD&C Green 3 Fast Green FCF 42035
Caramel Burnt sugar
Titanium dioxide – 77891
Colorants are obtained in two forms dyes and lakes.
 Dyes are dissolved in the binding solution prior to the granulating process. However, during drying
their color may migrate to the surface and may produce mottling of the tablet.
 So another approach is to adsorb the dye on starch or calcium sulfate from its aqueous solution; the
resultant powder is dried and blended with other ingredients.
 Color lakes are dyes which are adsorbed onto a hydrous oxide of a heavy metal (like aluminium)
resulting in an insoluble form of the dye.

FLAVOURS AND SWEETENERS

Flavours are usually limited to chewable tablets or other tablets intended to dissolve in the
mouth.
Flavor oils are added to tablet granulations in solvents, are dispersed on clays and other
adsorbents or are emulsified in aqueous granulating agents (i.e. binder).
N.B. Usually, the maximum amount of oil that can be incorporated to a granulation without influencing its tableting
characteristics is 0.5 to 0.75% w/v.
The use of sweeteners is primarily limited to chewable tablets.
E.g. Sugar
Mannitol – 72% as sweet as sugar, cooling & mouth filling effect
Saccharin – Artificial sweetener
500 times sweeter than sucrose
Disadvantages (i) it has a bitter after taste
(ii) Carcinogenic
Cyclamate – either alone or with saccharin
– It is banned
Aspartame (Searle) – widely replacing saccharin
– Disadvantage – lack of stability in presence of moisture

MANUFACTURE OF TABLETS
Manufacture of tablets involves certain well defined steps: namely,
Pulverization and mixing Granulation Compression Coating (if required)
PULVERIZATION AND MIXING

In this step the different

solid / powder ingredients
are reduced to the same
particle size since particles
of different sizes will
segregate while mixing.

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Instruments used for milling or size reduction:

General characteristics of various types of mills
Types of Mill Action used for Not used for
Cutter Cutting fibrous, crude animal friable material
and vegetable drugs
Revolving Action and impact fine grinding of soft material
abrasive materials
Hammer Impact almost all drugs abrasive materials
Roller Pressure soft material abrasive material
Attrition Attrition soft and fibrous abrasive material
material
Fluid energy mill attrition and impact moderately hard and soft and sticky material
friable material

For mixing dry powders following mixers are used:

GRANULATION
Objectives:
Simple powder may not have the desired flow property because there are may types of forces
acting between solid particles:
1. Frictional forces,
2. surface tension forces,
3. mechanical forces caused by interlocking of particles of irregular shapes
4. electrostatic forces and
5. Cohesive or van der Waals forces.
Though bulk density and shape of the particles are important but two of the most common experiments
done to get some idea about the flow property are
(i) Angle of repose and (ii) hopper flow rate measurement.
Values for angle of repose  300 usually indicate a free-flowing material and
Values of angle of repose  400 suggests a poorly flowing material.
Hopper flow rates have been used as a method to assess flowability of the powder mass. In this
method the flow of powder from a conical hopper is continually monitored by the flow of material out
of the hopper on to a recording balance device.
Question: “Mostly the materials, intended for compression into tablets are converted into
granules” – Why?
Ans: Materials intended for compaction into tablets must possess two characteristics:
(1) Fluidity and (2) compressibility.
Good flow properties are essential for the transport of the material through the hopper, into and through
the feed frame into the dies. Tablet materials should therefore be in a physical form that flows
uniformly and smoothly. The ideal physical form is sphere, since spheres offers minimum contact
surface between themselves and with the walls of the machine parts.
Unfortunately, most materials do not easily form spheres; however shapes approaching spheres
improve flowability. Hence flow properties of powder materials are improved by forming sphere like
regular shaped aggregates called granules.

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WET GRANULATION
Step-I Milling of the drug and excipients
 Milling of the active ingredients, excipients etc. are milled to obtain a homogeneity in the final
granulation.
 If the drug is given in solution then during drying it will come up to the surface. To avoid this
problem drug is mixed with other excipients in fine state.
Step-II Weighing
 Weighing should be done in clean area with provision of air flow system.
 In the weighing area all the ingredients must not be brought at a time to avoid cross-contamination.
Step-III Mixing
Commonly used blenders are: (a) Double cone blender
(b) V – blender
(c) Ribbon blender
(d) Planetary mixer
Any one of the blender may be used to mix dry powder mass.
Step-IV Wet Massing
Wet granulation forms the granules by binding the powders together with an adhesive.
Binder solutions can be added in two methods:
Method-I Method-II

Drug + Diluent Drug + Diluent

Dry binder is added Binder Solution is added

Blended uniformly

Suitable solvent is added to activate the dry binder

Blended in a Sigma - mixer or Planetary mixer

till properly wet mass is formed

 The powder must be moist and not paste.

 Blending may take 30 mins to 1 hour.

N.B.
 To determine the proper moistening, the moist mass is balled in a palm, pressed by two fingers, if
fragments of granules are formed and not powder then the blending is stopped.
 Since, in general, the mass should be moist rather than wet or paste, there is a limit to the amount
of solvent that may be incorporated.
Therefore, when
(i) A small quantity of solvent is permissible, method-I is adopted and
(ii) A large quantity of solvent is required method-II is adopted.
 However, method-II will give more cohesiveness than method-I if the amount of binder remains
constant.
 If granulation is over-wetted, the granules will be hard, requiring considerable pressure to form the
tablets, and the resultant tablets may have a mottled appearance.
 If the powder mixture is not wetted sufficiently, the resulting granules will be too soft, breaking
down during lubrication and causing difficulty during compression.

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Step-V Wet Screening

Wet screening process involves converting the moist mass into coarse, granular aggregates by
(i) Passage through a hand screen (in small scale production) or,
(ii) Passage through an oscillatory granulator of hammer mill equipped with screens having large
perforations (# 6 – 8 mesh screen).
Purpose (i) Increase particle contact point
(ii) Increase surface area to facilitate drying.
Step-VI Drying
 Drying is usually carried out at 600C. Depending on the thermolabile nature of the drug the
temperature can be optimized.
 Drying is required in all wet granulation procedures to remove the solvent, but is not dried
absolutely because it will pose problems later on. Hence, certain amount of moisture (1 – 4 %) is
left within the granules – known as the residual moisture.
Methods: Drying can be carried out
1. Tray dryers – it may take 24 hrs of drying
2. Truck dryers – the whole cabinet can be taken out of the dryer
3. Fluid-bed dryer – dried for 30 mins.
The total surface of the granules are dried uniformly but in tray dryer the lower surface of the granules
may not be dried uniformly. Case hardening may some time occur in tray dried products.

N.B. In case hardening the outer surface of the lumps of the wet powder will be dried quickly and become hard
(forming a hard crust), while the inner part will remain wet. This phenomenon is called case hardening.

Step-VII Dry Screening

After drying, the granule size is reduced by passing through smaller mesh screen.
 For drying granules the screen size to be selected depends on the diameters of the punch. The
following sizes are suggested:
Tablet diameter upto Mesh Size
3/16 ” # 20
3.5 / 16 – 5/16” # 16
5.5/16 – 6.5/16” # 14
7.0/16 or larger # 12
Step-VIII Lubrication of granules
 After dry granulation, the lubricant is added as a fine powder. It usually, is screened onto the
granulation through 60 or 100 mesh nylon cloth to eliminate small lumps as well as increase the
covering capacity of the lubricant.
 The lubricant is blended very gently using tumbling action to maintain the uniform granule size.
 Too much fine powder is not desirable because fine powder may not feed into the die uniformly
causing variation in weight and density.
 Since, the very nature of lubricant produce hydrophobic surface on the particle hence over blending
prevents the inter granule bonding that takes place during compression.

Example of wet granulation formulae:-

Ferrous sulfate tablets
Ingredients Quantity / tablet Remarks
Ferrous sulfate (dried) 300 mg Active ingredient
Corn Starch 60 mg Diluent
20% sugar solution q.s. Binder
Explotab 45 mg Disintegrant
Talc 30 mg Glidant & Antiadherent
Magnesium stearate 4 mg Lubricant

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Method of preparation

FeSO4 + Corn Starch

 Mix
 Moistened with sugar solution
 Passed through #12
Wet granules
 Dried on tray dryer (Temp: 60 – 650C, over night)
 Dry Screened through #18
Dry granules  Explotab + talc + Mg-stearate
 Compression
TABLET

DRY GRANULATION
Dry granulation is followed in situations where
(i) The effective dose of a drug is too high for direct compaction,
(ii) If the drug is sensitive to heat, moisture or both, which precludes wet granulation.
E.g. many aspirin and vitamin formulations are prepared for tableting by compression granulation.

Steps of granulations
Milling  Weighing  Screening  Blending  Slugging  Granulation (Dry)  Lubrication

Compaction

Slug:
Slug may described as poorly formed tablets or, may be described as compacted mass of powdered
material.
Purpose: To impart cohesiveness to the ingredients, so as to form tablets of desired properties.
Method: It is done either by (i) by high capacity heavy duty tablet press
(ii) Of by Chilsonator roller compactor.
(i) By high capacity tablet press large tablets are made because
(a) Fine powders flow better into large cavities, and
(b) Large slugs reduces production time
 The punches are flat faced
 Sufficient pressure should be applied.
 Powdered materials contains a considerable amount of air; under pressure this air is expelled and
fairly dense piece is formed. More time is allowed for this air to escape.
 The compressed slugs are comminuted in desired mesh screen.
 Lubricant is added twice : i.e.
1. During blending with other powders and
2. Added to the granulations
 The lubricant is blended gently with the granulation and is compressed into tablets

(ii) Chilsonator roller compactor

 Chilsonator consists of two grooved rollers. Powder is flowed into the grooves and compressed
mass is produced as the rollers rotates.
 Distance between two rollers can be adjusted.
 By the impeller always the air is removed from the powder mass.
 By using oscillatory granulator granules are prepared and lubricant is blended with the granules
and compressed into tablets.

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Advantages of chilsonator over tablet press

1. Very high production rate
2. Pressure can be controlled
3. Lubrication is not required in the primary stage.
Using a tablet press Using a chilsonator
Powder + Lubricant Powders
 
Slugs Slugs
 
Granules Granules
 
Lubricated Lubricated
 
Compressed Compressed
Hence, in a chilsonator only once lubricant is used. Since lubricants, such as talc, magnesium stearate
etc. are hydrophobic in nature they will
(i) Impart problem in in-vitro disintegration
(ii) Compaction will not be efficient due to the decrease in inter-particular cohesive force.

Advantages of dry granulation over wet granulation

1. No application of moisture (required in wet granulation) and heat (for drying). So the drugs
susceptible to either moisture or heat or both can be made by dry granulation. E.g. calcium lactate
cannot be used by wet granulation. (Aspirin, Vitamin C)
2. Dry granulation involves less steps and hence less time is required than that of wet granulation.
3. Less steps requires less working space and energy.
Since popularity of wet granulation is more that dry granulation because former will meet all the
physical requirement for the compression of good tablets.

Example of dry granulation

Preparation of Aspirin tablets
Ingredients Quantity required per tablet Remarks
Aspirin (#20 mesh) 325.0 mg Active ingredient
Starch (dried) 32.5 mg Diluent / Disintegrant
Cab-o-sil 0.1 mg Lubricant

Method:
Aspirin + Starch + Cab-o-sil
10 mins  mixed in twin-shell blender for 10 mins
Powder blend
 Compressed into slugs of 1 inch diameter flat-face punch
Slugs
 Size reduction by Oscillatory granulator
Granulation (# 16 mesh)

Compressed
N.B. All operations are carried out in a dehumidified area at a relative humidity less than 30% at 700F
(21.10C).

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DIRECT COMPRESSION
Steps:
Milling

Weighing

Sieving

Blending

Compression

Advantages: (i) It is much quicker than any of the previous process

(ii) Minimum number of steps are required.
Modified diluents, binders etc. are available in the market which assure spherical shape of the granules
to modify flow property. However, they are not used extensively.
1. If active medicament is less in amount then there will be no problem but in case of high dose large
amount of active ingredient is to be replaced by specially treated vehicles to improve flow property
or compressibility.
2. These specially treated materials are costly.

Example Vitamin B1 tablets

Ingredients Quantity for each tablet Remarks
Thiamine hydrochloride 100 mg Active ingredient
Avicel PH 102 83.35 mg Glidant
Lactose (anhydrous) 141.65 mg Diluent
Mg-stearate 6.65 mg Lubricant
Cab-o-sil 1.65 mg Lubricant

Method:
Vitamin B1 + Avicel + Lactose + Cab-o-sil

Mg-stearate + Mixture
 Mixed for 5 minutes
Compressed
N.B. Anhydrous lactose can be replaced with Fast Flo lactose which will reduce the requirement of
glidant (Avicel).

PROBLEMS FACED IN TABLETING

1. CAPPING AND LAMINATION

Capping is the partial or complete separation of the top or bottom crowns of a tablet from the
main body of the tablet.
Lamination is the separation of tablet into two or more distinct layers.
Usually these problems are apparent immediately after compression, or even hour or days later.
Detection: Subjecting tablets to the friability test is the quickest way to reveal such problems.
(a) Reason: Entrapment of excess air in the granules during compression. If the granules are light
and fluffy this type of problems are encountered frequently.
Remedies: Increasing the density of granules by adding more binder or changing the solvent of
binder.

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(b) Reason: New set of punches and dies are very tightly fitted; i.e. the clearance is very negligible
hence air cannot come out.
Remedy: In that case punch diameter should be reduced by 0.005” (i.e. 5 thou)
(c) Reason: Granules should not be completely dried. If over dried or under dried then capping may
take place.
Remedy: So moisture content should be kept within 1 – 2%.
(d) Reason: Concave punches, used for longer period of time will form claw-shaped curve – this
forms capping.
Remedy: Punches are changed.

2. PICKING AND STICKING

Picking and sticking are the removal of surface materials from a tablet by sticking to the punch faces.
Picking: When some portion of the surface of the tablet is removed – it is termed as picking.
Cause: When punch tips have engraving or embossing, usually of letters B, A, O are difficult
to manufacture cleanly. These may produce picking.
Remedy: (i) Lettering should be designed as large as possible, particularly on punches of small
diameter.
(ii) Plating of the punch faces with chromium produces smooth, non-adherent face.
(iii) Colloidal Silica (Cab-o-sil) is added as polishing agent that makes the punch faces
smooth; so that material does not cling to them.

Sticking: Sticking refers to tablet materials adhering to the die wall.

Disadvantages:
1. When sticking occurs, additional force is required to overcome the friction between tablet
and the die wall during ejection.
2. Serious sticking at ejection can cause chipping of a tablet’s edges and can produce a rough
edge.
3. Also, a sticking problem does not allow the lower punches free movement and therefore
can place unusual stresses on the cam tracks and punch heads, resulting in their damage.
4. Sticking can also cause build-up of material on punch faces.
Causes:
1. Excessive moisture may be responsible for sticking.
Remedy: Further drying of the granulation is then required.
2. During compression heat is generated and
(a) Low m.p. lubricants e.g. stearic acid may produce sticking.
Remedy: Low melting point lubricant are replaced with high melting point lubricants
(e.g. Poly ethylene glycol)
(b) Low m.p. substances, either active ingredients or additives may soften sufficiently form the
heat of compression to cause sticking.
Remedies:
 Dilution of active ingredient with additional high m.p. diluents.
 Increase in the size of tablet.
 If a low m.p. medicament is present in high concentration then refrigeration of the
granules and then compressing may be the order.

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3. MOTTLING
Mottling is an unequal distribution of color on a tablet, with light or dark patches in an
otherwise uniform surface.
Cause: Migration of water soluble dyes to the surface while drying.
Remedies:
 Change the solvent system.
 Change the binder system
 Reduce the drying temperature
 Grind to a smaller particle size.
 *** Use lakes instead of water soluble dyes.
QUALITY CONTROL OF COMPRESSED TABLET
Quality control of compressed tablet can be done by
(i) Official methods and
(ii) Unofficial methods.
1. WEIGHT VARIATION (Official)
This test is based on the fact that, if the weight variation is not much then it can be said that the
amount of medicament will not vary considerably. Conversely, if the weight variation is larger then it
can be concluded that the active medicament will also vary considerably.
Sources of weight variation
Weight variation is solely dependent on the poor flow property of granules and filling of die
cavity.
Poor flow properties arise from: (a) improper lubrication
(b) Size of granules
(c) Adjustment of lower punch.
Weight variation test
The U.S.P. weight variation test is run by weighing 20 tablets individually, calculating the
average weight, and comparing the individual tablet weights to the average. The tablets meet the USP
test if
“Not more than 2 tablets are outside the percentage limit and if
No tablet differs by more than 2 times the percentage limit.”

N.B.
Say 20 tablets weighed separately
Percentage limit is  10%.
Say the average weight was 100 mg.
Then the sample of tablets will pass the USP weight variation test if
18 tablets remain within 90 mg to 110 mg and
2 tablets remain within 80 mg to 120 mg.

The weight variation tolerance for uncoated tablets differ on average tablet weight.

Average weight of tablets (mg) Maximum percentage difference allowed

130 or less  10
130 to 324  7.5
More than 324 5

N.B. Weight of tablets: w1, w2, w3, wn.., w20.

Average weight of the tablets = w

So the weight variation of nth tablet =

 w  w  x 100%
n

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2. CONTENT UNIFORMITY TEST

N.B. Weight variation test is applicable when the amount of medicament in the tablet is high. In potent drug
the medicament is less in amount in comparison to the other excipients. The weight variation may meet the
Pharmacopoeial limitation but this will not ensure the correct variation of potency. Hence, in this case the
weight variation test is followed by content uniformity test.

Content uniformity test

In this test 30 tablets are randomly selected for sample, and at least 10 of them are assayed
individually according to the official assay method.
Nine of the 10 tablets must have potency within  15 % of the labeled drug content. Only one
tablet may be within  25%.
If this conditions are not met then the tablets remaining from the 30 must be assayed
individually and none may fall outside  15% of the labeled content.

N.B. For example:

30 tablets are taken at random
10 tablets are assayed individually
In which 8 tablets remained within  15%
And 2 tablets remained within  15 % and  25 %.
So the test has to be carried out with rest of the 20 tablets.
And those 20 tablets must remain within  15%.
Conclusion: Out of the 30 tablets the potency of only 2 tablets may remain within 15 to 25 % rest of all the
tablets should remain within 15%.

3. TABLET HARDNESS
The resistance of the tablet to chipping, abrasion or breakage under conditions of storage,
transportation and handling before usage depends on its hardness.
Method:
A tablet is taken between the 2nd and 3rd finger and pressing it with the thumb as fulcrum. If
the tablet breaks with a “sharp snap”, yet, it does not break when it falls on the floor – is said to
possess proper hardness.
Instruments used:
1. Monsanto Hardness Tester
2. Strong Cobb Hardness Tester Manual mode of operation are more or less similar
3. Pfizer Hardness Tester
4. Schleuniger Apparatus – Operates without manual involvement.

Hardness of a tablet:
The hardness at which the tablet crushes is the hardness of the tablet.
Unit of hardness: Kg/sq.in. Or lb/ sq.in
Limit: Generally maximum 5 kg/sq.in. Hardness is required.
N.B.
 If the tablets are too hard then it may not meet tablet disintegration test.
 If the tablets are too soft then it may not with stand the handling, packaging and shipping
operations.

4. FRIABILITY
Tablet hardness is not an absolute indicator of strength since some formulations, when
compressed into very hard tablets may produce chipping, capping and lamination problems. Therefore
another measure of tablet strength i.e. friability is often measured, i.e. the friability.

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Instrument: ROCHE FRIABILATOR 2 5 rp m

Objective of friability test: 4 m in s
This apparatus is designed to evaluate the ability of the
tablet to withstand abrasion, in handling, packaging and shipping
6"
operation.
Method:
Few tablets, previously weighed are taken in the plastic R o c h e F r ia b ila to r
chamber of the laboratory friability tester. In the plastic chamber the tablets are subjected to abrasion
and shock by rotating the plastic chamber at 25 rpm for 4 mins (i.e. total 100 revolutions). The tablets
are dusted and reweighed.
Limit
For conventional compressed tablet the weight loss should be within 0.5 to 1.0 %.

5. DISINTEGRATION TEST OF TABLETS (Official)

For most tablets, the first important step toward solution is breakdown of the tablet into smaller
particles or granules – this process is known as disintegration.
 The time a tablet takes to disintegrate is the disintegration time.
USP disintegration test apparatus
The USP device to test disintegration uses glass tubes with the following dimensions:
Number of tubes = 6
Length = 3 inches
Upper end open, lower end closed with #10 mesh screen.
To test the disintegration time one tablet is placed in each tube, and the basket rack assembly is
positioned in a 1-litre beaker of water, simulated gastric fluid or simulated intestinal fluid, at
370C20C, such that the tablet remain 2.5 cm from the bottom of the beaker.
A standard motor moves the basket up and down through a distance of 5 to 6 cm at a frequency
of 28 to 32 cpm (cycles per minute).
Perforated plastic discs may also be placed on top of the tablets to impart an abrasive action to
the tablets. They are useful for tablets that float.
 USP disintegration test will be passed if all the tablets disintegrate and the particles passed through
the #10 mesh screen within the specified time. If any residue remains, it must have a soft mass with
no palpable firm core.
 Disintegration time is suggested for 5 minutes for uncoated Aspirin tablets. Majority of the
uncoated tablets have maximum disintegration time (DT) of 30 minutes.
 Enteric coated tablets shows no evidence of disintegration after 1 hr in simulated gastric fluid. The
same tablets are then tested in simulated intestinal fluid and are to disintegrate in 2 hrs plus the time
specified in the monograph.

6. DISSOLUTION TEST

Why is it required?
1. Disintegration test simply identifies the time required for the tablet to break up under the condition
of the test but it does not ensure the drug release in the bulk of the fluid.
2. Rate of dissolution is directly related to the efficacy of the drug.
3. Rate of dissolution is a good index for comparing the bioavailability of two tablet products of the
same drug.

USP XX / NF XV, Supplement 3 specifies two apparatus for dissolution test.

1. Apparatus - I
In general, a single tablet is placed in a small wire mesh basket and immersed in the dissolution
medium (as specified in the monograph) contained in a 1000 ml flask at 370  0.50C. Generally it is
rotated at 50 rpm unless otherwise specified.

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2. Apparatus 2
The same equipment is used. Instead of basket a paddle is introduced as the stirring element.
The tablet is allowed to sink at the bottom of the flask before stirring.
Limit: A value of t90% (i.e 90% drug release) within 30 minutes is often considered satisfactory and is
an excellent goal since a common dissolution tolerance in the USP/NF is not less than 75% dissolved in
45 minutes.

TABLET COATING
Reasons behind coating of tablets:
The reasons behind coating of tablets are as follows:
1. To mask the taste, odour or colour of the drug. Improving the product appearance, particularly
where there are visible differences in tablet core ingredients from batch to batch.
2. Provide physical protection, facilitates handling, particularly in high speed packaging / filling lines.
3. To provide chemical protection from its surrounding environment (particularly air, moisture and
light).
4. To control the release of drug from the tablet e.g. sustained release tablets, repeat action tablets.
5. To protect the drug from the gastric environment of the stomach with an acid resistant enteric
coating.

Tablet properties (or Core properties)

Tablets that are to be coated are called core. This core must possess the proper physical characteristics.
1. In pan coating process the core tablets roll in the pan or cascade in the air stream in air suspension
coating. To endure the intense attrition between tablets or wall of the pan the tablets must have
enough hardness.
2. Sugar coating can mask the imperfection on the surface but film coating cannot, hence, for film
coating the core surface must be smooth.
3. The tablets must be in constant motion during the early drying phase or tablet agglomeration may
occur. The ideal shape for coating is a sphere; the worst shape is a square flat-faced tablet and in
practice rounded, convex shaped tablet cores are taken.
4. For coating materials to adhere to the tablet the coating composition must wet the surface of the
core. E.g. hydrophobic tablet surfaces are difficult to coat with aqueous-based coating.

TABLET COATING PROCESSES

Two types of tablet coating are popular –
(i) Sugar coating and (ii) film coating.

SUGAR COATING OF COMPRESSED TABLETS

The sugar coating process can be subdivided into six main steps:
1. Sealing
2. Subcoating
3. Smoothing (Syruping)
4. Color coating
5. Polishing and
6. Printing

1. Sealing

Objectives (i) To prevent moisture penetration into the tablet core, a seal coat is applied.
(ii) To strengthen the tablet core without a seal coat, the over wetted tablets would
absorb excess moisture, leading to tablet softening, and may affect the physical and
chemical stability.

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Ingredients  Alcoholic solutions of Shellac (10 – 30% solid) or

 alcoholic solution of zein,
 alcoholic solution of cellulose acetate phthalate (CAP) or
 Alcoholic solution of polyvinyl acetate phthalate.
N.B.
 With aging the disintegration and dissolution time is found to increase with shellac due to
polymerization
 Zein is an alcohol soluble protein derivative obtained from corn (maize).

2. Subcoating
Objectives To round the edges and build up the tablet size. Sugar coating can increase the tablet
weight by 50 to 100% at this step.
Method The subcoating step consists of alternately applying a sticky binder solution to the
tablets followed by a dusting of subcoating powders and then drying.
Subsequent coatings are applied in the same manner until the tablet edges have
been covered and the desired thickness is achieved.
Ingredients  Binder solution formulations for subcoating:-
Gelatin 3.3%(w/w)
Gum acacia (powder) 8.7%(w/w)
Sucrose 55.3%(w/w)
Water to 100%(w/w)
 Dusting powder formulation
Calcium carbonate 40.0%(w/w)
Titanium dioxide 5.0%(w/w)
Talc (asbestos free) 25.0%(w/w)
Sucrose powder 28.0%(w/w)
Gum acacia powder 2.0%(w/w)

3. Smoothing or syruping
Objectives To cover and fill in the imperfections in the tablet surface caused by the subcoating
step.
Ingredients Simple syrup solution (approximately 60 – 70 %( w/w)).
Often the smoothing syrups contain a low percentage of titanium dioxide (1 – 5%) as
an opacifier. This gives a very bright and reflective background for the subsequent
coloring step.

4. Colour coating
Objective To impart an elegant and uniform colour.
Ingredient Syrup (60 – 70% sucrose) containing the desired color.
Method Syrup solutions containing the dyes are coated upto 60 individual applications until the
desired color is achieved. After each application of color the coatings are dried.
In the finishing step a few clear coats of syrup may be applied.

5. Polishing
Objective To produce the desired luster on the surface of the tablet.
Ingredients Mixtures of waxes (like beeswax, carnauba wax, candella wax or hard paraffin).
Method Either this mixtures of waxes are applied as powder or as dispersions in various
organic solvents in a polishing pan (canvas line pan).

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6. Printing
In order to identify sugar-coated tablets often it is necessary to print them, using
pharmaceutical grade ink, by means of a process of offset rotogravure.
FILM COATING
Film coating adds 2 to 5% to the tablet weight.
Film coating can be done by the following three methods.
(i) Pan-pour method:
Viscous coating materials are directly added from some container into the rotating pan moving
with the tablet bed. Tablets are subjected to alternate solution application, mixing and then drying.
Disadvantages:
 The method is relatively slow.
 It relies heavily on the skill of the operator.
 Tablets always require additional drying to remove the latent solvent.
 Aqueous film coating are not suitable for this method because localized over wetting will produce
physicochemical instability.

(ii) Pan-spray method:

Coating material is sprayed over the tablet bed from nozzles and hot air is passed through the
tablet bed to dry it.
The variables to be controlled is pan-spray film coating process are:
(a) Pan variables:
Uniform mixing is essential to deposit the same quantity of film on each tablet.
1. Pan design or baffling:
Some tablet shapes mixes freely while other shapes may require a specific baffling arrangement
to ensure adequate mixing.
Disadvantages: Baffles may produce chipping and breakage if not selected properly.
(b) Pan speed
Pan speed affects mixing and the velocity at which the tablet pass under the spray.
 Too slow speed cause localized over-wetting resulting in tablets sticking to each other or to the pan.
 Too high speeds may not allow enough time for drying before the same tablets are reintroduced to
the spray. This results in a rough coating appearance on the tablets.
 Optimum pan speed: 10 – 15 rpm for nonaqueous film coating
3 – 10 rpm for aqueous film coating.
(c) Spray variables
1. Rate of liquid application
2. Spray pattern
3. Degree of atomization
These three spray variables are interdependent.
For spraying two types of systems are there:
(a) High-pressure, airless system and
(b) Low-pressure, air atomization system.
 The proper rate of liquid application depends on the mixing and drying efficiency of the system and
the coating formula.
 A band of spray should be spread evenly over the tablet mass. In larger pans, more nozzles must be
added to cover the tablet bed width.
A spray pattern that is too wide will apply coating on the pan.
A spray pattern that is too narrow will produce localized over-wetting.
Spray width can be adjusted by moving the nozzles closer or further away from the tablet bed.
 Atomization is the process where by the liquid stream is finely subdivided into droplets. The degree
of atomization (i.e. the size and size-distribution of the droplets). Too fine atomization causes some
droplets to dry before reaching the tablet surface, resulting in roughness on the tablet surface and

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excess dust in the pan. Too large atomization causes localized over-wetting – leads to sticking,
picking or a rough “orange peel” effect.

(d) Process air variables (temperature, volume, and rate) are required for optimum drying of the coating
by evaporation of the solvent.
The balance between the supply and exhaust air flow should be such that all the dust and
solvent are confined within the coating system.

(iii) Fluidized bed process (air suspension coating)

This process have been successfully used for rapid coating of tablets, granules and capsules.
Process variables are as follows:
(a) Chamber design and air flow rate controls the fluidization pattern.
(b) Tablet shape, size and density.
(c) Volume and rate of air flow
– Too high rate produce attrition and breakage of tablets
– Too low rate  mass does not move fast enough through the spray region  over-wetting occurs.
(d) Inlet and exhaust air temperature.

DEVELOPMENT OF FILM COATING

Before coating a tablet the coating formula is first cast on either a glass, Teflon or aluminium
foil surface. Glass is preferred for cast films. The coating is done by spreading with a glass rod. After
drying, the cast films are assessed for the following properties:
(i) Physical appearance – potential colorant or opaquant separation is noted.
(ii) Lack of color uniformity
(iii) Insoluble additives have been properly suspended or not.
(iv) Water vapor permeability
(v) Film tensile strength

MATERIAL USED FOR FILM COATING

Film formers

Nonenteric materials : e.g. Hydroxypropyl methylcellulose (HPMC)

Methylhydroxy ethyl cellulose (MHEC)
Ethylcellulose (EC)
Hydroxypropyl cellulose (HPC)
Polyvinyl pyrrolidone (PVP)
Sodium carboxymethyl cellulose (Sod. CMC)
Polyethylene glycols (PEG)
Acrylate polymers e.g. Eudragit E

Enteric materials: e.g. Cellulose acetate phthalate (CAP)

Acrylate polymers (Eudragit L, S)
Hydroxypropyl methylcellulose phthalate (HPMCP)
Polyvinyl acetate phthalate (PVAP)

Solvents
Criteria
1. It should either dissolve or disperse the polymer system.
2. It should easily disperse other coating solution components into the solvent system.
3. Small concentration of polymers (2 to 10%) should not result in an extremely viscous solution
system (> 300 cps), creating process problems.

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4. It should be colorless, tasteless, odourless, inexpensive, non-toxic, inert and non-inflammable.

5. It should have no environmental impact.
Colorants: Same as tablet.
Opaquant extenders:
Very fine inorganic powders e.g.
Titanium dioxide (TiO2)
Silicates like talc, aluminium silicate
Carbonates like magnesium carbonate
Sulfates like calcium sulfate
Oxides like magnesium oxide and
Hydroxides like aluminium hydroxides.

Miscellaneous coating solution components

Flavors and sweeteners
Surfactants are used to solubilize immiscible or insoluble ingredients
Antioxidants
Antimicrobial agents.

FILM DEFECTS
Variations in formulation and processing conditions may result in unacceptable quality in the
film coating. Some of the problems are as follows:

Picking
Overwetting or excessive film tackiness or when the drying system is inefficient – tablets stick
to each other or to the coating pan. On drying, at the point of contact, a piece of the film may remain
adhered to the pan or to another tablet, giving a “picked” appearance to the tablet surface and resulting
in a small exposed area of the core tablet.
Remedy:
 A reduction in the liquid application rate or,
 Increase in the drying air temperature and air volume usually solve this problem.
 If excessive tackiness is there then the formulation is changed.

Roughness
A rough or gritty surface is a defect often observed when the coating is applied by spray. Some
of the droplets may dry too rapidly before reaching the tablet bed, resulting in droplets on the tablet of
“spray dried” particles instead of finely divided droplets of coating solution.
Roughness also increases with pigment concentration and polymer concentration.
Remedy
 Moving the nozzle closer to the tablet bed
 Reducing the viscosity of coating solution.

Bridging and filling

During drying, the film may shrink and pull away from the sharp corners of a bisect, resulting
in “bridging” of the surface depression.
This defect may be so severe that the monogram or the bisect is completely obscured.
This is a problem in the formulation.
Remedy
 Increasing the plasticizer amount in the formulation
 Changing the plasticizer can decrease the incidence of bridging.
Filling: If the solution is applied too fast, over-wetting may cause the liquid to quickly fill and be
retained in the monogram – this is called filling.

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Remedy
 Judicious monitoring of the fluid application rate, and
 Thorough mixing of the tablets in the pan prevent filling.
Blistering
When coated tablets require further drying in ovens, too rapid evaporation of the solvent from
the core and the effect of high temperature on the strength, elasticity and adhesion of the film may result
in blistering.
Remedy Milder drying conditions are adopted.

Hazing / Dull film (Bloom)

It can occur when too high a processing temperature is used for a particular formulation. It is particularly
evident when cellulosic polymers are applied out of aqueous media at high processing temperatures.
It can also occur if the coated tablets are exposed to high humidity conditions and solution of film results.

Color variation
 Improper mixing, uneven spray pattern.
 Insufficient coating may result in color variation.
 The migration of soluble dyes, plasticizers, and other additives during drying may give the coating
a mottled or spotted appearance.
Remedy
 Use of lake instead of dye.
 Changing the plasticizer and additives.
Cracking
Cracking occurs if the internal stresses in the film exceed the tensile strength of the film. The
tensile strength of the film can be increased by using higher molecular weight polymers or polymer
blends.
Internal stresses in the film can be minimized by adjusting the plasticizer type and
concentration, and the pigment type and concentration.
Plasticizers
These are used to impart flexibility to the film.
e.g. Castor oil, propylene glycol, glycerin,
Polyethyleneglycol (PEG) 200 and 400,
Surfactants e.g. polysorbates (Tweens), Sorbitan esters (Spans) and organic esters.
1. Ques: Draw a sketch of the layout of a tablet manufacturing unit. Differentiate between capsule unit and this.

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TABLETS DOSAGE FORM IMPORTANT POINTS FOR GPAT EXAM

 90% of drugs are in oral dosage form.

 Tablet is unit dosage form.
 Liquid dosage forms r given in dose of medication 5-30%.
 Tablet should have 2-4% of moisture.

EVALUATION
 GENERAL APPEARANCE
 Size and shape – compressed tablets shape and dimensions are determined by the tooling
during the compression process.
Rem-when compression force is constant, tablet thickness varies with changes in die fill,
with particle size distribution, packing of particle mix and tab. Weight.
When die fill is constant, thickness varies with variation in compressive load.
 Crown thickness of tablet measured by Micrometer.
 Total crown thickness is measured by Vernier calliper.
 Tablet thickness should be controlled with ±5% of std. Value.
 The more the convex the tablet surface more is the capping problem so one has to use
slower tablet machine or one with pre compression capabilities.
 Unique identification markings-given in Physicians’ Desk Reference (PDR).
 Product code is given from National Drug Code (NDC).
 Mottling-non uniformity of colour over tablet surface.
 For colour quantification 3 methods-reflectance spectrophotometry, tristimulus
colorimetry and micro-reflectance photometry.
 Hardness and Friability
 Hardness of tablet directly effects dissolution behaviour.
 It is the force req. to break the tablet in diametric compression test.
 Hardness also called crushing strength.

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 Devices used
 Monsento tester (stockes tester)-easy to handle. Manually operated, gives strength in kgs.
 Strong-cobb tester-force applied by hydraulic pressure and later air pressure not manually.
It gives value 1.6 times higher than the original strength.
 It gives strength in kgs.
 Pfizer tester-same principle as pair of pliers.(kgs)
 Two testers to eliminate operation variations:-
1. Erweka tester-gives strength in Kgs.
2. Schleuniger tester-operates in horizontal position-gives strength in KGs and
Strong Cobb units.
 Hardness and thickness of tablet is a function of die fill and compression force.
 At constant compression force, hardness increase with increasing die fill.
 At constant die fill, hardness increase and thickness decrease when compression force is applied.
 Roche friabilator machine is used for measuring friability of tablet.
Tablets fall from-6 inch distance
Total RPM -25, Total revolutions – 100, Time - 4 minutes
Limits- 0.5-1.0% (USP), not more than 1% (IP).
 Effervescent tablets and chewable tablets show higher friability value than above so
stack packaging for them.
 Vickers test is used to measure the surface hardness.
 ‘Whiskering’ phenomenon is related with tablets with deeply concave surfaces or punches
used were in poor condition and such tablets have higher than normal friability values.
HARDNESS LIMITS
TABLET HARDNESS LIMIT

SOFT 2 KG

SUSTAINED RELEASE 8 KG

GENERAL 4 KG

HARD 6 KG

EFFERVESCENT 1.3 KG

STANDARD HARDNESS SHOULD BE MIN. 4 KG

Webster and Van Abbe tester-indicate edge damage during handling.

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 WEIGHT VARIATION
 Total tablets taken-10.
 Limits -Tablets meet USP if not more than 2 tablets are outside the limit and no tablet
should differ by more than 2 times the original limit.
 This test is used if the tablet contains 90-95% API. It is not appropriate for low dose
containing tablets. API should be more than 50mg. (i.e-potency).
 For these content uniformity test is used.
USP LIMITS
AVERAGE WT OF TABLETS(MG) MAX. % DIFF. ALLOWED
130 or less 10
130-324 7.5
More than 324 5

I.P LIMITS
AVERAGE WT OF TABLETS (MG) MAX. % DIFF. ALLOWED
80 or less 10
80-250 7.5
More than 250 5

 CONTENT UNIFORMITY TEST:

 It should be between 95-105%.
 Tablet potency for this test should be less than 50mg.
 For digitoxin it is 90-110%.
 If larger wt. Variation, no good content uniformity.
Test:
 Total tablets-30
 Total assayed-at least 10
 9 of the tablets should contain 85-115% API.
 10th tablet may contain 75-125% API. Test passed
 If above conditions not met other 20 tablets should be assayed, and no one should
fall outside 85-115% range.

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 DISINTEGRATION
APPARATUS
 6 test tubes
 Mesh size: 10 mesh i.e 1.7mm (USP), 8 mesh i.e 2mm (IP)
 Glass tubes are 3 inches long
 Beaker contains 1L of water, simulated gastric fluid or simulated intestinal fluid.
 Temperature: 37±2 degree Celsius. (Remember with reference to difference with dissolution)
 Tablets remain 2.5 cm below surface of liquid on upward movement and vice versa.
 No. of cycles per minute: 28-32
IP LIMITS

Tablet/Capsule Liquid Disintegration time(min)

Uncoated tablet Water 15 min (USP-30 min)

Sugar coated Water 60 min

2 hr in gastric fluid media and
0.1N HCl with phosphate
Enteric coated 1 hr in intestinal fluid(USP it
buffer
is reverse)

Film coated Water or 0.1N HCl 30 min

Vaginal tablets Water 30 min

Soluble, dispersible and Water
3 min
effervescent tablets (19-21 deg. Celcius)
Hard gelatin capsules Water 15 min
Soft gelatin capsules Water 60 min

 DISSOLUTION
USP
Apparatus 1-Basket type
Mesh screen-10 mesh (USP)
Temperature: 37±0.5 degree Celsius. 900 ml flask.
Apparatus 2-paddle type
900 ml. Flask.
Contains wire helix to prevent tablet from floating.

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Limits (USP)
 Not less than 75% should be dissolved in 45 min.
 90% of the drug should be dissolved in 30 min.(this is not USP limit, it is industrial limit)
 Above both values are Q values.
 Dissolution acceptance criteria(IP)
Stage No. Of dosage Acceptance criteria
units tested
S1 6 No dosage unit is less than Q+5%.
S2 6 Average of 12 dosage units is equal to or not more than Q% and no
unit is less than Q-15%.
S3 12 Average of 24 dosage units is equal to greater than Q% and not
more than 2 dosage units are less than Q-15% and no dosage unit is
less than Q-25%.

TABLET COMPRESSION APPARATUS

 Dies define shape and size of tablet.
 Cam tracks guide the movement of punches.
 Multi-station presses are called rotary presses.
 Turrets-the portion of the head that hold the upper and lower punches.
 Fette machines-they chill the compression components to allow compression of low
melting solids such as waxes use (in case of suppositories0.

TOOLING
 BB tooling-most commonly used.length-5.25 inch,
 Nominal barrel diameter-0.75 inch, 1 inch head diameter.
 B tooling-5.25 inch, nominal barrel diameter-3 9/16 inch, 1 inch head diameter.
 D tooling-used for larger tablets. 5.25 inch,
 Nominal barrel diameter-1 inch, 1.25 inch head diameter.
 Dwell time-time for which tablet remains under compression.
 Remember-Devices which measure compression force at each compression station.
 Pharmakontroll,
 Killiani Control System,
 Thomas Tablet Sentine

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 PROCESSING PROBLEMS IN TABLET

1) Capping and lamination-capping is partial or complete separation of top or bottom parts
of tablet from main body of tablet.
Lamination is separation of tablet into 2 or more distinct layers. It is due to:-
 Deformational properties of formulation i.e plastic deformation
 Deep concave punches.
 Absence of adequate moisture.
 Tablet tooling
 Incorrect setting of press.
2) Picking and sticking- Picking occurs due to engraving and embossing.
In sticking tablet material sticks to die wall.
3) Mottling- uneven distribution of color on tablet.
4) Weight Variation
5) Poor flow- Talc or colloidal silica helps in improving the flow.
Poor flow can result in bridging, arching and rat holling.
6) Poor mixing
7) Punch variation
8) Hardness variation
9) Double impression
 TABLET GRANULATION
 It improves flow properties of tablet.
 Shape factor of granule should be 6 just like sphere for good flow.
 The method used for measurement of surface area solid granules or particles are air
permeability method and gas-adsorption method (He gas is used).
 Dense granules require higher compression force to form cohesive compact and they are less
friable.
 For determining granule density-Mercury displacement method is used.
 Other method uses benzene as organic solvent.
 As granule size increase bulk density decreases.
 As particle becomes more spherical bulk density increases.
 The strength of tablet is mainly due to surface tension of liquid and capillary forces.
 For measuring granule strength and friability ASTM (American Society for Testing
Materials) specification is taken into account and compression strength are taken into account.

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 TYPES OF GRANULATION
 DRY GRANULATION
 Also called compression granulation.
 Used when drug is sensitive to moisture.
 Slugs are formed in this.so process also called slugging.
 Roller compactor instrument is used. Can produce 500 kg of slugs.
 Main advantage is that no need to use excess lubricants.
 WET GRANULATION
 Granules formed by adhesive forces.
 Surface tension forces and capillary pressure are initially responsible for wet granulation.
 Solvents are used considering EPA (Environmental Protection Agency) regulations.

EQUIPMENTS FOR WET GRANULATION

1. Littleford Lodige mixer- Capable of both wet massing and blending.
 Time taken-30-60 sec.
 Horizontal in operation.
 Temperature rise of 10-15 deg. is expected.
2. Diosna mixer or granulator- contains bowl in vertical position.
 Total time 11-12 min.
3. Littleford MGT mixer- vertical in operation.
4. Gral mixer- Modification of planetary mixer (IMP).

 DIRECT COMPRESSION
 Eg. NaCl, KCl can be directly compressed.
 Uses directly compressible diluents like spray dried lactose.
 They have good flow and compressibility.
 Maximum of 30% of API is used in direct compression tablet.

 TABLET INGREDIENTS
 DILUENTS:
 Used to increase bulk of tablet.
 5-80% can be used.

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 All the sugar containing diluents have tendency to undergo reaction with drugs containing –
NH2 group. This is called Maillard reaction which only changes color not content.

STARCH
 11-14% moisture present
 Dried starch has 2-4% moisture.
 Their moisture level increase to 6-8% following moisture exposure.
 Two types:
1) Directly compressible starch (Sta-Rx 1500)-used as diluents, binder and disintegrant.
Contains 10% of moisture.
2) Hydrolysed starch (Emdex, Cellutab: contain 90-92% dextrose and 3-5% maltose)-
directly compressible. Used in chewing tablets and have 8-10% of moisture.

LACTOSE
Three types of lactose.
1) Alfa-lactose monohydrate - Crystalline nature, has 5% moisture, poor flow and
compressibility and used in wet granulation. It gives Maillard reaction.
2) Spray dried lactose - <3% moisture. Good flow and compressibility. Used in direct
compression.it gives Maillard reaction. (In Maillard reaction furfuraldehyde is formed).
3) B-lactose (anhydrous) - hygroscopic. Used in direct compression and does not gives
Maillard reaction.
DEXTROSE
 Also called cerelose.
 Can be used instead of lactose.

MANNITOL
 Used in chewable tablet due to negative heat of solution.
 Non-hygroscopic.
 Non-cariogenic.
 Used in vitamin formulations.
SORBITOL
 Optical isomer of mannitol.
 Hygroscopic.

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SUCROSE
Available as co-processed form such as
SUGARTAB (90-95% sucrose + 7-10% invert sugar),
DIPAC (97%sucrose + 3% modified dextrin)
NUTAB (95%sucrose + 4% invert sugar + Mg. stearate + corn starch).
Used in direct compression.
Hygsroscopic
Important point-Kaolin and bentonite, diluents, is not used with cardiac glycoside, synthetic
estrogens and alkaloids.

MICROCRYSTALLINE CELLULOSE (MCC)

 Trade name- AVICEL
 DIRECTLY COMPRESSIBLE
 Two grades: PH 101(powder) and PH 102(granules)
 Also act as disintegrating agent.
 Hygroscopic in nature.
 May delay the release of drug.

DICALCIUM PHOSPHATE (DCP)

 Non-hygroscopic (Just like mannitol)
 Moisture sensitive drugs can be used with it
 Not used with tetracycline due to complex formation.

CLASSIFICATION IN OTHER WAY

 Wet granulating diluents- alfa lactose, kaolin, bentonite, dicalcium sulphate
 Direct compression- Spray dried lactose, colloidal silica, NaCl and NaHCO3 for
dental cones, direct com. starch.
 Binders and adhesives
Used to provide cohesive qualities.
More the binder, harder is the tablet.

NATURAL GUM
 Acacia and tragacanth are examples
 Used in 10-25%

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GELATIN
 Natural protein
 10-20% in solution form.
 Upon storage disintegration time will increase with the use of such binders Starch
 10-20%solution.
 Give translucent paste.
 It undergoes hydrolysis to dextrin and glucose.
 Liquid glucose is 50%solution in water.
Modified natural polymers
 Methylcellulose (alcohol soluble, more soluble in cold water than hot water)
 Hydroxy propylcellulose HPC (alcohol sol.)
 Hydroxy propyl methylcellulose HPMC (water soluble)
 Ethylcellulose EC (alcohol soluble, retard D.T)
 PVP (polyvinyl pyrrolidone) used in 2%.used in aqueous and alcoholic solution.
 IPA (isopropyl alcohol)-widely used binder.

 ANOTHER CLASSIFICATION
 Solution binders- Starch, Sucrose, Gelatine, Acacia, Tragacanth.
 Dry binders- HPMC. Cross linked PVP.

 LUBRICANTS
 Decrease friction between diewall and tablet surface
 Can be used intragranularly (PEG, Vegetable oils) and extragranularly (talc, stearates).
 They are hydrophobic in nature.
 Fluid lubricant-liq. Paraffin
 Boundary lubricant-stearic acid

 What is bolting of lubricant?

Lubricant is passed through 60-100 mesh nylon cloth in order to get fine particles this is
called bolting of lubricant.
 Hydrocarbon/mineral oil
 Applied as fine spray.
 Mostly used for aspirin tablets

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 Calcium and Mg. Stearate

 used in 1%
 may cause delay release
 Mg.stearate is used with SLS due to its hydrophobic property.
 It is not used with acidic drugs

 COMPRITOL 888
 It is glyceryl monoester of behenic acid.
 Water soluble lubricants
 Sodium Benzoate, sodium acetate, NaCl, leucine, PEG etc.

 GLIDANTS
1) TALC
 Used in 5%.
 Can also be used as anti-adherent.
 Contains traces of iron so may act as catalyst for the drugs which are degraded by Fe.
 Also contain calcium so not used with tetracycline.

2) COLLOIDAL SILICA
Available in 3 forms
1. Cab-o-sil (<1%)
2. Aerosil (0.25-3%)
3. Syloid.

3) CORN STARCH
 Use in 5-10%
DISINTEGRANTS

 Facilitate breaking up of tablet Act by 3 mechanism

1. By swelling - Alginate, starch dye, PVP
2. By wetting - SLS, Clay, Bentonite
3. Effervescent - NaHCO3 and citric acid

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EXAMPLES
STARCH
 5-20%
 Modified starches are used which are: Primogel and Explotab.
 they are low substituted carboxymethyl starches.(1-8% used, but 4%is optimum)

 CLAYS
 Veegum (Mg. Aluminium silicate) (10%)
 Bentonite (10%)
 both are used only for colored tablets
 They are most effective in sulfathiazole tablets.

 SUPER DISINTEGRANTS
 They are used in lower concentration. of 2 % to 6 %,
 while traditional disintegrants such as starches often require concentrations of about 20 %.

Sodium Starch Glycolate Sodium Carboxymethyl Starch

Croscarmellose Sodium Soy Polysaccharides

 Primojel®, sodium starch glycolate, and Primellose®, croscarmellose sodium, which show
outstanding disintegration characteristics for tablets prepared by direct compression, wet
granulation and for capsule formulations.

COLORING AGENTS
 Lake are the dyes that have absorbed on hydrous oxide
 As coloring concentration increases, mottling increases.
 To improve photosensitivity of dye use of UV absorbing chemical such as
benzophenone can be used.
 DI-PACLINE is a commercially available directly compressible sugar.

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SWEETENERS
 Used in (0.5-0.75%)
 Cyclamates can be used.
 Cyclamates is 70 times sweeter than sugar. But are carcinogenic
 Aspartate (phenyl ester of methylacetic acid).
 Aspartam180-200 times sweeter than sugar and non-carcinogenic.
 Saccharin is carcinogenic and 500 times sweeter than sugar.
 Mannitol is used in chewable tablets and 72 times sweeter than sugar.

SOME INSTRUMENTS
MIXING
 For large qt. Of powder-twin-
 Shell blender
 Double-cone blender,
 Planetary mixer.
 For continuous production
 Ribbon blender
 Rotocabe-blender
 Mass mixer
 Sigma blade mixer
 High speed granulators
 Diosna mixer,
 Littleford MGT,
 Gral mixer
 For continuous production extruders are used E.g. Reitz extruders
 Topo granulators to prepare granules under high vaccum.
 Spheronization refers to formation of spherical particle from wet granulation.
 Marumerizer and CF-granlator are used for Spheronization.

 SPRAY CONGEALING/SPRAY CHILLING

 It is the process consist of melting solid and reducing them to beads or powders by
spraying molten feed into stream of colder air or gases.
 Monoglycerides are spray congealed at 50 deg F
 Carbohydrates are spray congealed at 167 deg F

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 IMPORTANT INFORMATION
 Versa press is used for the preparation of layered tablets.
 Manestey dry cota instrument is used.
 Implantation tablets should have size of less than 8mm.
 Kern-injector-contain hollow needle and plunger.
 It is used for administration of rod shaped tablet.
 For sub-lingual and vaginl tablets, lactose is used as diluent.

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PHARM AROCKS GPAT SUCCESS TEST SERIES-2016 SOLID DOSAGE FORM CAPSULE

CAPSULES

Syllabus:
Principles, materials and equipment involved in the formulation and filling of hard gelatin capsules and their
quality requirements, layout of capsule section. Account of soft gelatin capsules.

DEFINITION
Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft, soluble
container or shell of a suitable form of gelatin.

Advantages of capsule dosage forms

1. They obscure the taste and odour of unpleasant drugs.
2. They are attractive in appearance.
3. They are slippery when moist and, hence, easy to swallow with a draught of water.
4. If properly stored, the shells contain 12-15% of moisture which gives flexibility and, consequently very
considerable resistance to mechanical stresses (cf. cachets).
5. Less adjuncts are necessary than tablets.
6. The contents are usually in fine powder which combined with adjuncts, provides rapid and uniform release of
medicament in the GIT.
7. The shells can be opacified with TiO2 or coloured to give protection from light.
8. The shells are physiologically inert and easily and quickly digested in the GIT.
9. Presentation of a drug in capsules, rather than in tablets, allows quicker submission of a new drug for clinical
trials, because fewer development problems are involved. Also it is easier to vary the dose.
Disadvantages of capsule dosage forms
1. Capsules are not used for administering extremely soluble materials such as potassium chloride, potassium
bromide, or ammonium chloride since sudden release of such compounds in the stomach could result in
irritation.
2. Capsules should not be used for highly efflorescent or deliquescent materials.
 Efflorescent materials may cause the capsules to soften.
 Deliquescent materials may dry the capsule shell to excessive brittleness.
MATERIALS
Capsules are made principally of gelatin blends and may contain small amounts of certified dyes, opaquing
agents, plasticizers and preservatives.
To modify the solubility of the capsules (e.g. to impart enteric property) methyl cellulose, polyvinyl alcohols and
denatured gelatin are used.

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GELATIN
 Gelatin is a heterogeneous product derived by irreversible hydrolytic extraction of treated animal collagen
(obtained from animal skin and bone).
 Common sources of collagen are animal bones, hide portions, and frozen pork skin.
 There are mainly two types of gelatin commercially available:
Type A: Gelatin is derived mainly from pork skin by acid treatment. This gelatin has an isoelectric point in
the region of pH 9.
Type B: Gelatin is derived from bones and animal skins by alkaline processing (pH 4  5).
B Dry bone  5% HCl  Lime 10%  Lime  pH
10 - 15 days 4-8 weeks removal adjustment
B Calf skin  wash  Lime 10%  Water wash
6-12 weeks
A Pork skin  wash  Acid 1-5% HCL Acid removal
10-30hrs

Hot water  Filter  Vacuum  Cool to  Air dry  Mill

Extraction concentration solidify to size.
Blends of Gelatin A and Gelatin B are used.
 Bone gelatin produces a tough, firm film, but tends to be hazy and brittle.
 Pork skin gelatin contributes plasticity and clarity to the blend, hence bone gelatin and pork skin gelatin are
generally used in blends.

Method of production of empty hard gelatin capsule shells

1. Hundred and fifty (150) pairs of stainless mold pins (on which capsule is formed) are dipped into a gelatin
sol (melted gelatin) of carefully controlled viscosity to form the caps and bodies simultaneously.
2. The pins are usually rotated to distribute the gelatin uniformly during which time the gelatin may be set or
gelled by a blast of cool air.
3. The pins are moved through a series of controlled air drying kilns for the gradually and precontrolled removal
of water.
4. The capsules are stripped from the pins by bronze jaws and trimmed to length by stationary knives while the
capsule halves are being spun in chucks or collets.
5. After being trimmed to exact length, the cap and body sections are joined and ejected from the machine.
The entire cycle of the machine lasts approximately 45 minutes.

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CAPSULE SHAPE
1. Simple telescoping hard gelatin capsules Body moves easily inside the cap
Disadvantages
(a) Body can come out of the cap easily spilling over the powder inside.
(b) In high speed capsule filling machines capsules may split and/or denting of the
capsule shell may occur.
2. Gelatin seal fuses the two capsule halves to create a one-piece capsule that is
tamper proof.

3. in the body:-
(a) Tapered rim is provided to prevent splitting / denting.
(b) Grooves which interlock the two halves together once the capsule has been
filled.
(c) Indentations to prevent premature opening.

CAPSULE SIZE
Empty gelatin capsules are manufactured in various sizes, varying in
length, in diameter, and capacity.
Their capacities vary with the bulk-density of the contents and the
pressure applied during filling.
For human use, empty capsules ranging in size from 000, the largest, to
5, the smallest are commercially available.

CAPSULE NUMBER AND VOLUME FILL IN IT

Capsule No. 000 00 0 1 2 3 4 5

Approx. Vol
1.50 0.90 0.75 0.55 0.40 0.30 0.25 0.15
(ml)

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CAPSULE FILLING EQUIPMENT

There are several equipment available in the market but they may be classified into two classes depending on the
mode of operation.
 Lily, Parke-Davis, Höfliger and Karg, Osaka and Perry
 Zanasi, Macofar, Farmatic and mG2 equipment

LILY TYPE CAPSULE FILLING EQUIPMENT

Number of operators required = 1
Number of capsule output = 200,000 capsules / day
(a) The empty capsules are fed from the storage
hopper (1) and through the rectifying unit (2), into
the two-piece filling ring (3A and 3B).
Rectification is based on dimensional differences
between the outside diameters of the cap and body
portions of the capsule.
(b) As the ring (3A and 3B) is rotated, a vacuum is applied on its underside. The vacuum sucks the bodies into
the lower half of the ring, while the caps are retained in the upper portion. The two pieces of the ring are
separated, and the cap-containing portion is placed aside.
(c) The body containing portion of the ring is placed on a variable speed turntable and is mechanically rotated
under the powder hopper (4), which contains an auger for the forced delivery of the powder.
(d) After one (or more) complete rotations of the rings, the powder hopper (4) is removed, and the two segments
of the ring (3A and 3B) are rejoined.
(e) The intact ring is positioned in front of the peg ring (5) and the closing plate (6) is pivoted to a positioned
approximately 1800 from the position showed in the figure. Pneumatic pressure is applied to the peg ring (5),
which forces the caps in position.
(f) After opening the closing plate 96) the capsules are ejected through the portion of the ring by giving slight
hand pressure against the peg ring.
(g) The filled capsules are collected through the chute (7) into a collection chamber.
 Highest turntable speed: minimum total fill weights
Maximum weight variation
 Lowest turntable speed: maximum total fill weights
Minimum weight variation

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ZANASI CAPSULE FILLING MACHINE

 No. of operators required = 0 (automatic)
 No. of capsules output = 4000 to 150,000 capsules / hr.
 In this type of equipment the empty capsule shells come down from hopper through individual tubes and
rectified. The capsule shells are seated in a holder with the body downward. Vacuum assists its
placement.
 Another vacuum is applied over the top of the holder to separate the cap from the body of the capsule.
 The cap containing half is moved aside. The lower part of the holder is exposed for filling.
 The powder is continuously mixed within the powder hopper and is maintained at a constant level prior
to change.
 A set of volumetric dosing nozzles, each of which picks up the product from the constant level container,
first compressing and then ejecting the powder into the capsule bodies.
 The cap holder half is repositioned over the block and closing is accompanied by both upper and lower
closing pins.
 Ejection is accomplished by compressed air.
PREPARATION OF FILLED HARD GELATIN CAPSULES
The preparation of filled hard gelatin capsules may be divided into the following steps.
1. Developing and preparing the formulation and selecting the size of the capsule.
2. Filling the capsules shells.
3. Cleaning and polishing the filled capsules.

CAPSULE FORMULATION
In developing a capsule formulation, the goal is to prepare a formulation that results in accurate dosage, good
bioavailability characteristics, and ease of capsule filling during production.
(a) To achieve uniform drug distribution throughout the powder mix the density and particle size of the
drug and excipients should be similar.
If required the particle size may be reduced by milling.
Then the drug and excipients are blended thoroughly to get a uniform powder mix.
(b) The powder mix must provide the type of flow characteristics required by the equipment.
 In case of Lily type equipment powder must be free flowing e.g. with acetyl salicylic acid flowable corn
starch is used.
 In case of Zanasi type equipment powder must have sufficient cohesiveness to retain its slug form during
delivery to the capsules. E.g. with acetyl salicylic acid compactible excipients such microcrystalline cellulose
are required.
 Lubricant such as, magnesium stearate can be used in Lily type and binders like mineral oil can be used in
Zanasi type capsule filling equipments.

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(c) Selection of capsule size.

(i) When the dose of the drug is large and the diluent is not required or negligible in quantity, the size may be
selected after the development and preparation of the formulation.
(ii) When the capsule is meant for young or elderly patients the capsule size (smaller size) is selected first and
then formulation is prepared. If required the dose may be divided into two capsules.
(iii) A properly filled capsule should have its body filled with the drug mixture and its cap fully extended down
the body  a capsule size should be selected to meet this requirement.
FILLING THE CAPSULE SHELLS
(a) Manual punch method
For filling a small number of capsules in a dispensary pharmacists generally use punch method.
 Precise number of empty hard gelatin capsule shells are taken.
 The powder is taken on a clean sheet of paper or glass or porcelain plate. With a spatula a cake is formed
with the powder having a height of approximately 1/4 to 1/3 the length of the capsule body.
 Then the empty capsule body is held between thumb and forefinger and “punched” vertically into the powder
cake repeatedly until filled. The capsule bodies are capped.
 After capping the capsules are weighed to ensure accurate filling.
(b) Filling can be done by hand-operated capsule filling machine, Lily and Zanasi type capsule filling machines.
Lily is semi-automatic and Zanasi is fully automatic.
[For details see the equipment - how they are filled]
CAPSULE SEALING
To make the capsules “tamper evident” (previously the term was “tamper resistant”) two types of sealing
processes are there
(i) Banding: The two capsule parts are sealed with a gelatin or polymer band at the seam of the cap and body.
(ii) The contact areas of the cap and body are wetted with a mixture of water and ethanol and then thermally
bonded at 40 to 450C.
Capsule sealing equipment may be linked with capsule filling equipment to maintain production levels of
upto 150,000 capsules per hour per unit.

CLEANING AND POLISHING

After filling some powder formulation may adhere to the outside of the capsules. This powder
 may be bitter or unpalatable,
 May reduce the appearance of the capsule.
Methods of cleaning
1. Pan polishing: The Accela-Cota tablet coating pan may be used to clean and polish capsules. A polyurethane
or cheese cloth liner is placed in the pan, and the liner is used to trap the removed dust as well as to impart a
gloss to the capsules.

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2. Cloth dusting: In this method, the bulk filled capsules are rubbed with a cloth that may not be impregnated
with an inert oil. Though it is a hand operation but by this method
(a) large volume of capsules can be polished,
(b) Powders too resistant to remove by other methods can be removed easily by this method.
(c) It imparts a somewhat improved gloss to the capsules.

3. Brushing: In this procedure, capsules are fed under rotating soft brushes, which serve to remove the dust from
the capsule shell. This operation is accompanied by a vacuum for dust removal.
e.g. ROTOSORT it removes loose powder,
Removes unfilled joined capsules
Removes capsules with loose caps
Erweka KEA  dedusting and polishing
Scidenader PM60  for cleaning and polishing

SOFT GELATIN CAPSULES

Advantages of soft gelatin capsules:
(i) Soft gelatin capsules are useful when it is desirable to seal the medication within the capsule.
(ii) The capsules are especially important to contain liquid drugs or drug solutions.
(iii) Also, volatile drug substances or drug materials especially susceptible to deterioration in the presence of air
may be better suited to a soft gelatin capsule than hard gelatin capsules.
(iv) Soft gelatin capsules are elegant and are easily swallowed by the patients.
CAPSULE SIZES AND SHAPES
Shape Diagram Size range (number represents the nominal capacity in
minims (1 cc = 16.23 minim)
Round 1,2,3,4,5,6,7,9,28,40,90,

40T,80T

Oval 1,2,3,4,5,6,7.5,10,.12,16,20,30,40,60,80,85,110.

3,4,5,6,8,9.5,11,14,16,20,90,360
Oblong

55,65,90,160,250,320,480
Tube

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MATERIALS
The capsule shell is basically composed of gelatin, a plasticizer and water. It may contain additional ingredients
such as preservatives, coloring and opacifying agents, flavours, sugars, acids and medicaments to achieve desired
effects.

GELATIN
The gelatin should be of USP grade and it should have some additional specifications, namely, bloom strength,
viscosity and iron content of the gelatin used.
Bloom or gel strength
It is a measure of the cohesive strength of the cross-linking that occurs between gelatin molecules and is
proportional to the molecular weight of the gelatin.
Determination
6 2/3 % gelatin gel kept at 100C for 17 hours
A plastic plunger having diameter 0.5 inch.
Bloom strength = the weight (in gram) required to move the plastic
plunger in the Gelatin mass upto 4 mm.
 Normally for soft-gelatin capsules the bloom strength of gelatin required
ranges from 150 to 250 g.
In general with all the other factors being equal, the higher the Bloom
strength of the gelatin used, the more physically stable is the capsule shell.
 Cost is, in general, proportional to Bloom strength; hence, higher Bloom
strength gelatins are only used when necessary to improve the physical stability of the product or large
capsules (over 50 minims).

Viscosity of gelatin
Viscosity of a 6 2/3 % gelatin in water solution at 600C is a measure of the molecular chain length and
determines the manufacturing characteristics of the gelatin film.
General range of viscosity 25 to 45 mill poise, it may be within narrow range 38  2 millipoise.
Iron content
Iron is always present in new gelatin, and its concentration usually depends on the iron content of the
large quantities of water used in its manufacture.
Limit: Gelatin used for soft gelatin capsules should not contain more than 15 ppm of iron.
Disadvantages:
(i) Iron may react with the certified dyes.
(ii) It may react with organic compounds to produce color (e.g. with phenolic compounds).

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PLASTICISERS
Very few plasticisers are used for soft gelatin capsules
(i) Glycerin USP
(ii) Sorbitol USP or
(iii) A combination of glycerin and sorbitol
The ration by weight of dry plasticiser: dry gelatin determines the ‘hardness’ of the gelatin shell.
TYPICAL SHELL HARDNESS AND THEIR USES.

Hardness Ratio of Dry glycerin / Usage

Dry gelatin
Hard 0.4 / 1 Oral, oil-based, or shell-softening products and those
destined primarily for hot humid areas. Oral, tube, vaginal

Oil-base, water-miscible-base, or shell hardening products

Medium 0.6 / 1 and those destined for temperate areas (hot & humid areas)
Tube, vaginal

Water-miscible base or shell hardening products and those

Soft 0.8 / 1 destined primarily for cold, dry areas.

ADDITIONAL COMPONENTS OF THE GELATIN MASS

Ingredients Concentration Purpose
Category-I
Methyl paraben 0.2 % Preservative
Propyl paraben (4 : 1) q.s.

FD&C and D&C water-soluble dyes, 0.2 to 1.2 %

certified lakes, pigments, vegetable 0.1 % Colorants
colours

Titanium di-oxide 2% Opacifier

Ethyl vanillin, Essential oils Flavor

Category-II To produce chewable shell and taste

Sugar (sucrose) to 5 % Aids solubility reduces aldehydic
Fumaric acid to 1 % tanning of gelatin

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NATURE OF THE CAPSULE CONTENT

Soft gelatin capsules can be used to dispense a variety of liquids, Solids, Combination of miscible liquids,
Suspension of solids in liquids.
Selection of capsule size
The maximum capsules size and shape for convenient oral use in humans is the 20 minims oblong, 16 minims
oval or 9 minims round
Types of liquids for encapsulation in soft gelatin capsules
1. Water, ethanol, and emulsion  these are water miscible or volatile components and they cannot be included
as major constituents of capsule since they can migrate into the hydrophilic gelatin shell and volatile from the
surface.
2. Gelatin plasticizers like glycerin, propylene glycol cannot be major constituents of capsules owing to their
softening effect on the gelatin shell.
3. Upto 10% glycerin and / or propylene glycol can be used as co-solvents with PEG or other liquids that have a
shell-hardening effect when capsulated alone.
Most widely used liquids for human comsumptions are
 Oil active ingredients e.g. clofibrate
 Vegetable oils e.g. soybean oil
 Mineral oil, non-ionic surfactants e.g. polysorbate 80 and PEG (400 and 600) either alone or in combination
 Fish oils in vitamin capsules.

Other conditions for manufacturing soft gelatin capsules

1. The suspension products must be homogeneous, air free and preferably should flow by gravity at room
temperature but not a temperature above 350C because the sealing temperature of gelatin films is usually 37
to 400C.
2. pH should be in between 2.5 and 7.5, since preparations that are more acidic can cause hydrolysis and
leakage of the gelatin shell, and preparations those are more alkaline can tan the gelatin and thus affect the
solubility of the shell.

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CAPSULE MANUFACTURING
Plate process: It is the oldest process, contains sets of plates containing die packets.
Rotary die process
Reciprocating die process
Accogel machine is unique in that it is the only equipment that accurately fills powdered dry solids into soft
gelatin capsules.

PROCESS
Gelatin preparation department
(i) Weighing of gelatin Mixed in
Weighing of other liquids  chilled at 70C Pony mixer
(ii) The resultant fluffy mixture transferred to melting tanks and melted under vacuum at 930C
(iii) A sample of the resulting fluid mass is visually compared with a color standard, and additional
colorants are added if required.
(iv) The mass is then maintained at 57 to 600C before and during capsulation process.

Material preparation department

(i) Blending  milling or homogenization

Equipments: Homoloid mill
Stone mill
Hopper mill
Urschel comitrol
(ii) Deaeration all mixtures are subjected to deaeration by
To achieve uniform capsule fill weight
And it reduces oxidation of the product.
Most liquids and suspensions may be deaerated by means of equipment designed to expose thin layers of the
material continuously to a vacuum (29.5 mm Hg).
(iii) After deaeration the volatile ingredients are added and blended.

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Material filling by rotary die process

 The gelatin mass is fed by gravity to a metering
device (spreader box), which control the flow of the
mass onto air cooled (13 to 140C) rotating drums.
Gelatin ribbons of controlled thickness are formed.
The wet film thickness may vary from 0.022 to
0.045 inch.
 The ribbons are fed through mineral oil lubricating
bath, over guide rolls, and then down between the
wedge and the die rolls.
 The materials to be encapsulated flows by gravity
into a positive displacement pump. The pump
accurately meters the material through the leads and
wedges and into the gelatin ribbons between the die
rolls. The bottom of the wedge contains small
orifices lined up with the die pockets of the die rolls.
 The capsule is about half sealed when the pressure
of the pumped material forces the gelatin into the die pockets, where the capsules are simultaneously filled,
shaped, hermetically sealed, and cut from the gelatin ribbon. The sealing of the capsule is achieved by
mechanical pressure on the die rolls and the heating (37 to 400C) of the ribbons by the wedge.
 Immediately after the manufacture, the capsules are automatically conveyed through a naphtha wash unit to
remove the mineral lubricating oil.
 The washed capsules may be automatically subjected to a preliminary infrared drying step which removes 60
to 70% of the water that is to be lost, or may be manually spread directly on trays. All the capsules are
allowed to come to equilibrium with forced air conditions of 20 to 30 % relative humidity at 21 to 240C.

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PREFORMULATION
Definition:
Preformulation may be described as a phase of the research and development process
where the preformulation scientist characterizes the physical, chemical and
mechanical properties of a new drug substance, in order to develop stable, safe and
effective dosage form.
Objectives:
The preformulation investigations confirm that there are no significant barriers to the
compound’s development as a marketed drug. The formulation scientist uses these
informations to develop dosage forms.
Preformulation is a multidisciplinary development of a drug candidate. See TABLE-1

Principal areas of preformulation

1. Bulk characterization
(i) Crystallinity and polymorphism
(ii) Hygroscopicity
(iii) Fine particle characterization
(iv) Powder flow
2. Solubility analysis
(i) Ionization constant – pKa
(ii) pH solubility profile
(iii) Common ion effect – KSP.
(iv) Thermal effects
(v) Solubilization
(vi) Partition coefficient
(vii) Dissolution
3. Stability Analysis
(i) Stability in toxicology formulation
(ii) Solution stability
– pH stability profile
(iii) Solid state stability
– Bulk stability
– Compatibility

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1. Bulk characterization
When a drug molecule is discovered all the solid-forms are hardly identified. So during
bulk characterization the following characteristics are studied.
(i) Crystallinity and polymorphism
Chemical Compounds

Habit Internal Structure

Crystalline
Amorphous

Single Entity Molecular Adduct

POLYMORPHS

Non-stoichiometric Stoichiometric
Inclusion compounds solvates / hydrates

Channel Layer Cage

(Clathrate)

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TABLE –1
Medicinal Chemistry Preformulation Formulation Process Research Analytical Research Toxicology and
And Pharmacology Research Development And Development And Development Drug Metabolism

Drug Discovery
Literature Search
Preliminary Data
– stability assay
Molecular Optimization – key stability data
– salts and solvates – key solubility data
– prodrugs

Evaluation and Selection of Drug

Time Increasing

Formulation Request

Physical Characterization Process Research Analytical Research

– bulk properties – improve yield – assay development
– solubility profile
– stability profile
– alternate route
– produce bulk
Analytical Bioavailability
Formulation Development
Process Development Development – in vivo models
– compatibility and stability
– bulk scale-up – bulk clearance
– dissolution – toxicology
– bioavailability potency Toxicology
– acute
– formulation assay – chronic
Phase-I Formulation – IND formulation
– IND stability stability
– Bioavailability
– Scale-up

Investigational New Drug (ND) Application

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 Flowability of powder and chemical stability depends on the habit and internal
structure of a drug.

Habit is the description of the outer

Needle or Acicular
appearance of a crystal. A single
Platy
Tabular
internal-structure for a compound can
have several different habits, depending
Bladed
on the environment for growing crystals.
Equant or Massive
Different habits of crystals are given Fig. 1 Prismatic
below.

Internal Structure

Crystalline state
In this state of matter atoms or molecules are arranged in highly ordered form and is
associated with three-dimensional periodicity.

[N.B. Atoms or molecules tend to organize themselves into their most favorable
thermodynamic state, which under certain conditions results in their appearance as crystals.
N.B. The repeating three-dimensional patterns are called crystal lattices. The crystal lattice
can be analyzed from its X-ray diffraction pattern.]

Amorphous forms
In this forms the solids do not have any fixed internal structure. They have atoms or
molecules randomly placed as in a liquid.
e.g. Amorphous Novobiocin
[N.B. Amorphous forms are prepared by rapid precipitation, lyophillization or rapid cooling
of molten liquids e.g. glass]

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DIFFERENCE BETWEEN CRYSTALLINE AND AMORPHOUS FORM

Crystalline forms Amorphous forms

(i) Crystalline forms have fixed internal (i) Amorphous forms do not have any fixed
structure internal structure
(ii) Crystalline forms are more stable than its (ii) Amorphous form has higher
amorphous forms. thermodynamic energy than its crystalline
(iii)Crystalline forms are more stable than its form.
amorphous forms. (iii) Amorphous forms are less stable than its
(iv) Crystalline form has lesser solubility than crystalline forms.
its amorphous form. (iv) Amorphous forms have greater solubility
(v) Crystalline form has lesser tendency to than its crystalline forms.
change its form during storage. (v) Amorphous tend to revert to more stable
forms during storage.

Polymorphs
When a substance exists in more than one crystalline form, the various forms are
called Polymorphs and the phenomenon as polymorphism.

E.g. Chloramphenicol palmitate has three polymorphs A, B and C.

[N.B. various polymorphs can be prepared by crystallizing the drug from different drugs
under diverse conditions. Depending on their relative stability, one of the several
polymorphic forms will be physically more stable than the others. Such a stable polymorph
represents the lowest energy state, has highest melting point and least solubility. The
representing polymorphs are called metastable forms which represents higher energy state,
the metastable forms have a thermodynamic tendency to convert to the stable form. A
metastable form cannot be called unstable because if it is kept dry, it will remain stable for
years.]

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Molecular Adducts
During the process of crystallization, some compounds have a tendency to trap the
solvent molecules.
1. Non-Stoichiometric inclusion compounds (or adducts)
In these crystals solvent molecules are entrapped within the crystal lattice and the number
of solvent molecules are not included in stoichiometric number. Depending on the shape they
are of three types:-
(1) Channel
When the crystal contains continuous channels in which the solvent molecule can be
included. E.g. Urea forms channel.
(2) Layers: - Here solvent molecules are entrapped in between layers of crystals.
(3) Clathrates (Cage):- Solvent molecules are entrapped within the cavity of the crystal from
all sides.

2. Stoichiometric inclusion compounds (or stoichiometric adducts)

This molecular complex has incorporated the crystallizing solvent molecules into specific
sites within the crystal lattice and has stoichiometric number of solvent molecules complexed.
When the incorporated solvent is water, the complex is called hydrates and when the
solvent is other than water, the complex is called solvates. Depending on the ratio of water
molecules within a complex the following nomenclature is followed.
(i) Anhydrous : 1 mole compound + 0 mole water
(ii) Hemihydrate: 1 mole compound + ½ mole water
(iii) Monohydrate: 1 mole compound + 1 mole water
(iv) Dihydrate : 1 mole compound + 2 moles water

Properties of solvates / hydrates

(i) Generally, the anhydrous form of a drug has greater aqueous solubility than its hydrates.
This is because the hydrates are already in equilibrium with water and therefore have less
demand for water. E.g. anhydrous forms of Theophyline and ampicillin have higher
aqueous solubility than the hydrates.
(ii) Non aqueous solvates have greater aqueous solubility than the non-solvates. E.g.
chloroform solvates of Griseofulvin are more water soluble than their nonsolvate forms.

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ANALYTICAL METHODS FOR CHARACTERIZATION OF SOLID FORMS

Methods of studying solid forms are listed as below:

Method Material required per sample

Microscopy 1 mg
Hot stage microscopy 1 mg
Differential Scanning Calorimetry (DSC) 2 – 5 mg
Differential Thermal Analysis (DTA) 2 – 5 mg
Thermogravimetric Analysis 10 mg
Infrared Spectroscopy 2 – 20 mg
X-ray Powder Diffraction 500 mg
Scanning Electron Microscopy 2 mg
Dissolution / Solubility Analysis mg to gm

Microscopy
In this type of microscope light passes through cross-polarizing filters.
Amorphous substances (e.g. super-cooled glass and non-crystalline organic compounds or
substances with cubic crystal lattices e.g. NaCl) have single refractive index. Through this
type of microscope the amorphous substances do not transmit light, and they appear black.
They are called isotropic substances.
Hot-stage microscopy
In this case, the polarizing microscope is fitted with a hot stage to investigate
polymorphism, melting points, transition temperatures and rates of transition at controlled rates.
It facilitates in explaining the thermal behavior of a substance from the DSC and TGA
curves.

[N.B. A problem often encountered during thermal microscopy is that organic molecules can
degrade during the melting process, and recrystallization of the melt may not occur, because
of the presence of contaminant degradation products. ]

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Thermal Analysis

Differential Thermal Analysis

In DTA instrument a record Exothermic peak
is produced where temperature
T
difference (T) (between the
sample and reference material) is Endothermic peak
plotted against temperature (T) Fig 2.
T
when two specimens are subjected
to an identically controlled temperature regime.
The reference material is alumina, keiselguhr.

Differential Scanning Calorimetry

In DSC method the difference in energy inputs (H) into a sample and reference
material is measured as a function of
Polymorphism of Phemobarbitone studied by DSC
temperature as the specimens are subjected
to a identically controlled temperature
programme. H Fig. 3

Samples that may be studied by DSC or 150 160 170 180 190

T
DTA are:
Powders, fibres, single crystals, polymer films, semi-solids or liquids.

Applications of DTA / DSC in preformulation studies

1. To determine the purity of a sample
2. To determine the number of polymorphs and to determine the ratio of each
polymorph.
3. To determine the heat of solvation
4. To determine the thermal degradation of a drug or excipients.
5. To determine the glass-transition temperature (tg) of a polymer.

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Thermogravimetric Analysis (TGA)

TGA measures the changes in sample weight as a function of time (isothermal changes) or
temperature.

% Weight
Application of TGA in preformulation study Remaining

1. Desolvation and decomposition Fig. 4

processes are monitored. 40 Temperature 170

2. Comparing TGA and DSC data

recorded under identical conditions can
greatly help in the explanation of the thermal process.

TGA and DSC analysis of an acetate salt

of an organic amine that has two
crystalline forms, anhydrous and
dihydrate are shown above. Anhydrous /
dihydrate (10:1) mixture was prepared by
dry blending. Heating rate was 50C/min.
From DSC curve, it is evident
that the dihydrate form loses two
molecules of water via an endothermic
transition between 700C and 900C. The
second endotherm at 1550C corresponds
to melting process.
From TA curve, it is evident that
at 70 – 900C weight-loss was due to the
loss two molecules of water and the
weight loss at 1550C was due to vaporization of acetic acid and decomposition.

X-RAY POWDER DIFFRACTION

When a X-ray beam falls on a powder the beam is diffracted. This diffraction in found only in
case of crystalline powder. Amorphous forms do not show X-ray diffraction.

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Uses:
(i) Each diffraction pattern is characteristic of a
6 Fig. 6
specific crystalline lattice for a given compound.
5
So in a mixture different crystalline forms can be 4
Intensity 3
analyzed using normalized intensities at specific
2
angles.
1
(ii) Identification of crystalline materials by using their
20 40 60 80 100
diffraction pattern as a ‘finger print’. First, the % From B
powder diffraction photograph or diffractometer trace are taken and matched with a
standard photograph. All the lines and peaks must match in position and relative intensity.

HYGROSCOPICITY
Definition: Many pharmaceutical materials have a tendency to adsorb atmospheric moisture
(especially water-soluble salt forms). They are called hygroscopic materials and
this phenomenon is known as hygroscopicity.
Equilibrium moisture content depends upon:
(i) The atmospheric humidity
(ii) Temperature
(iii) Surface area
(iv) Exposure time
(v) Mechanism of moisture uptake.
Deliquescent materials:
They absorb sufficient amount of moisture and dissolve completely in it.
(e.g. anhydrous calcium chloride).

Tests of hygroscopicity
powder sample
desiccator
Procedure shallow
container
Bulk drug samples are placed in open
saturated salt
containers with thin powder bed to assure solution
maximum atmospheric exposure. These Fig. 7

samples are then exposed to a range of controlled relative humidity (RH) environments
prepared with saturated aqueous salt solutions.

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The amount of moisture adsorbed can be determined by the following methods:

(i) Gravimetry
(ii) Thermogravimetric analysis (TGA)
(iii) Karl-Fischer titration (KF-titration)
(iv) Gas chromatography (GC)
Time of monitoring depends on the purpose:
(i) For the purpose of ‘handling’ data points from 0 to 24 hours are taken
(ii) For the purpose of ‘storage’ data points from 0 to 12 weeks are taken.

Significance of hygroscopicity test

(a)

To decide special handling procedure

mg H 2O % weight
g sample gain (with respect to time).

time time
Fig. 8

(b)

Equilibrium
moisture To decide
content Fig. 9
(i) the storage condition i.e. at low humidity environment.
mg H 2O
g sample
(ii) special packaging – e.g. with desiccant.
RH
(c) Moisture level in a powder sample may affect the flowability and compactibility which,
are important factors during tableting and capsule filling.

(d) After adsorption of moisture, if hydrates are formed then solubility of that powder may
change affecting the dissolution characteristics of the material.
(e) Moisture may degrade some materials. So humidity of a material must be controlled.

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FINE PARTICLE CHARACTERIZATION

Parameters those are measured:
(i) particle size and size-distribution
(ii) shape of the particle
(iii)surface morphology of the particles
Instrumental methods of particle size characterization

(i) Light microscope

First a standard graticule (BS 3625) is standardized with a stage micrometer. Then
small number of particles are spread over a glass slide and placed on the stage of the
microscope. Particles are focussed and the particle diameters are measured. Several hundred
particles are measured and reported as a histogram.
Disadvantage: The procedure is time consuming.

(ii) Stream counting devices

Examples: (a) Coulter counter – electrical sensing zone method
(b) HIAC – counter – optical sensing zone
(c) Malvern particle & droplet sizer – Laser diffraction method.

Procedure: To vacuum
Samples prepared for analysis are dispersed in a
conducting medium (e.g. saline) with the help of
ultrasound and a few drops of surfactant (to disperse the
To amplifier
particles uniformly). A known volume (0.5 to 2 ml) of and counter

this suspension is then drawn into a tube through a small

aperture (0.4 to 800 m diameter) across which a voltage Stirrer

is applied.
As each particle passes through the hole, it is counted and . . .. Electrodes
sized according to the resistance generated by displacing . .. . .
. . . Orifice
that particle’s volume of conducting medium. .
. . .. .
Size distribution is reported as histogram.
Fig. 10 Coulter counter

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(iii) Sieve analysis

A powder sample is passed through a standard sieve set. The particle size is plotted against
% weight retained on each sieve.
Use: This method is used generally for large samples.

Instrumental method for determination of specific surface area

Brunauer, Emmett and Teller (BET) nitrogen adsorption method:
A layer of nitrogen molecules is adsorbed to the sample surface at –1960C. Once the
surface is saturated, the sample is heated to room temperature, the nitrogen gas is desorbed,
and its volume is measured and converted to the number of adsorbed molecules via the gas
law. Since each N2 molecule occupies an ara of 16 A2, one may readily compute the surface
area per gram of each pre-weighed sample.
Instrumental method for characterization of surface morphology
The scanning electron microscope creates the magnified images by using electrons instead of
light waves. The images are black and white.
Procedure
 Biological materials are dried in a special way that prevents them from shrinking.
 Since SEM illuminates them with electrons, they are made conductive by coating with a
very thin layer of gold by a machine called sputter-coater.
 The sample is placed inside the microscope’s vacuum column through an airtight door.
 After the air is pumped out of the Electron gun
column, an electron gun emits a beam Vacuum column
of high-energy electrons. This beam Condensing
Monitor
lenses
travels downward through a series of
magnetic lenses designed to focus the
Scan coils
electrons to a very fine spot.
 Near the bottom, a set of scanning Objective lens
coils moves the focussed beam back Secondary
Electron
and forth across the specimen, row by Electron
beam
row.
Target Detector &
 As the electron beam hits each spot on Amplifier
the sample, secondary electrons are
Fig. 11 Scanning Electron Microscope
knocked loose from its surface.

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 A detector counts these electrons and sends the signals to an amplifier.

 The final image is built up from the number of electrons emitted from each spot on the
sample.

BULK DENSITY
Apparent Bulk Density (g/cm3)
Bulk drug powder is sieved through 40 mesh screen. Weight is taken and poured into a
graduated cylinder via a large funnel. The volume is called bulk volume.
Weight of the powder
Apparent Bulk Density 
Bulk Volume
Tapped density (g/cm3)
Bulk powder is sieved through 40 mesh screen. Weight is taken and poured into a graduated
cylinder. The cylinder is tapped 1000 times on a mechanical tapper apparatus. The volume
reached a minimum – called tapped volume.
Weight of the powder
Tapped density 
Tapped volume
True density (g/cm3)
Solvents of varying densities are selected in which the powder sample is insoluble. Small
quantity of surfactant may be mixed with the solvent mixture to enhance wetting and pore
penetration. After vigorous agitation, the samples are centrifuged briefly and then left to
stand undisturbed until floatation or settling has reached equilibrium.
The samples that remains suspended (i.e. neither suspended not floated) is taken. So the true
density of the powder are equal. So the true density of the powder is the density of that
solvent. The density of that solvent is determined accurately with a pycnometer.
Source of variation of bulk density
Method of crystallization, milling, formulation.
Methods of correction
By milling, slugging or formulation.
Significance
(i) Bulk density
Bulk density is required during the selection of capsule size for a high dose drug.
In case of low dose drug mixing with excipients is a problem if the bulk densities of
the drug and excipients have large difference.

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(ii) Tapped density

Fig. 12
Knowing the dose and tapped 000 1.4

density of the formulation, the 00 1.2

capsule size can be determined. 0 1.0

Capsule 8
Capsule
1
size volume
2 6 (ml)
(iii) True density 3 4

From bulk density and true 4

5 2

density of powder, the void 0.4 0.5 0.6 0.7 0.8 0.9
Packed density (g/ml)
volume or porosity can be
measured.

 m m   1 1 
Void volume      m   
  bulk  ture    bulk  true 
 1 1 
m   
  true   1   bulk
  bulk
Void volume
Porosity 
Bulk volume m  true
 bulk

Powder flow properties

Powder flow properties depends on
(i) particle size
(ii) density
(iii)shape
(iv) electrostatic charge and adsorbed moisture

That may arise from processing or formulation.

A free-flowing powder may become cohesive during development. This problem may be
solved by any of the following ways.
(i) by granulation
(ii) by densification via slugging
(iii)by filling special auger feed equipment (in case of powder)
(iv) by changing the formulation.

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Procedure Fig. 13
For free flowing powder
g/sec
A simple flow rate apparatus consisting of a
grounded metal tube from which drug flows through an time

orifice onto an electronic balance, which is connected to a Nozzle Plotter

Powder
strip chart recorder. Several flow rate (g/sec) determinations
at various orifice sizes (1/8 to ½ inch) should be carried out.
The grater the standard deviation between multiple
flow rate measurements, the greater will be the weight Digital Balance
variation of the product (tablets or capsules).
Compressibility :-
t  0
% compressib ility  x 100
t
t = tapped bulk density
0 = Initial bulk density

Solubility Analysis

Determination of equilibrium solubility of a drug

Equilibrium
solubility conc.
The drug is dispersed in a solvent. The
Plateau Fig. 14
suspension is agitated at a constant temperature. Conc.
Samples of the suspension are withdrawn as a
function of time, clarified by centrifugation, and Time

assayed to establish a plateau concentration.

Solvents taken
(i) 0.9% NaCl at room temperature
(ii) 0.01 M HCl at RT
(iii) 0.1 M HCl at RT
(iv) 0.1 M NaOH at RT
(v) At pH 7.4 buffer at 370C

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Drug concentration is determined by the following analytical methods

(i) HPLC
(ii) UV –Spectroscopy
(iii)Fluorescence Spectroscopy
(iv) Gas Chromatography

Solubility depends on
(i) pH
(ii) Temperature
(iii)Ionic strength
(iv) Buffer concentration

Significance
(i) A drug for oral administrative should be examined for solubility in an isotonic saline
solution and acidic pH. This solubility data may provide the dissolution profile invivo.
(ii) Solubility in various mediums is useful in developing suspension or solution
toxicologic and pharmacologic studies.
(iii) Solubility studies identify those drugs with a potential for bioavailability problems.
E.g. Drug having limited solubility (7 %) in the fluids of GIT often exhibit poor or
erratic absorption unless dosage forms are tailored for the drug.

pKa Determination

When a weakly acidic or basic drug partially ionizes in GI fluid, generally, the unionized
molecules are absorbed quickly.
Handerson-Hasselbalch equation provides an estimate of the ionized and unionized drug
concentration at a particular - pH.
HA + H 2O H3O+ + A
For acidic Drug:
Weak Strong
e.g. acid base

[ionized ] [ A ] [base]
pH  pKa  log  pKa  log  pKa  log
[unionized ] [ HA] [acid ]

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For basic compounds e.g.

B + H 3O+ BH + + H2O
Weak Strong
base acid

[unionized] [ B] [base]
pH  pKb  log  pKa  log  pKa  log
[ionized] [ BH  ] [acid]

Drug Stomach Plasma Duodenum

PH 1.5 PH = 7.4 PH = 5.0

[HA] = 100 [HA] = 100 [HA] = 100

Weak acid
e.g. Ibuprofen
[A --] = 0.13 [A--] = 100,000 [A--] = 398.1
pKa = 4.4
[Total] = 100.13 [Total] = 100,100 [Total] = 498.1

[B] = 100 [B] = 100 [B] = 100

[BH +] = 5012 [BH +] = 0.006 [BH +] = 1.6

[Total] = 5112 [Total] = 100.006 [Total] = 101.6

Weak base
e.g. Nitrazepam
pKa = 3.2

Method of determination of pKa of a drug

(i) Detection of spectral shifts by UV or visible spectroscopy at various pH.

Advantage: Dilute aqueous solutions can be analyzed by this method.
(ii) Potentiometric titration
Advantage: Maximum sensitivity for compounds with pKa in the range of 3 to 10.

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Disadvantage: This method is unsuccessful for candidates where precipitation

of the unionized forms occurs during titration. To prevent precipitation
a co-solvent e.g. methanol or dimethylsulfoxide (DMSO) can be
incorporated.
(iii) Variation of solubility at various pH.

Effect of temperature on stability

Heat of solution, HS represents the heat released or absorbed when a mole of solute is
dissolved in a large quantity of solvent.

Significance
 Most commonly, the solubility process is endothermic, e.g. non-electrolytes, unionized
forms of weak acids and bases  H is positive  Solubility increases if temperature
increases.
 Solutes that are ionized when dissolved releases heat
 the process is exothermic  HS is negative  Solubility increases at lower
temperature.

Determination of HS.
H S  1 
The working equation ln S      C where, S = molar solubility of the
R T 
drug at T0K
and R = gas constant
S is detemined at 50C, 250C, 370C and 500C.
HS = – Slope x R s
Slope =
R
lnS

Solubilization 1

For drug candidates with poor water solubility, T

preformulation studies should include limited experiments to identify the possible
mechanisms for solubilization.

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Means of increasing the solubility are:

(i) Addition of a cosolvent to the aqueous system e.g. ethanol, propylene glycol and glycerin.
MOA: These co-solvents disrupt the hydrophobic interactions of water at the non-
polar solute / water interfaces.
(ii) Solubilization in micellar solutions such as 0.01 M Tween 20 solution.
(iii) Solubilization by forming molecular complexes e.g. benzoic acid forms complex with caffeine.

Partition coefficient
Partition coefficient is defined, as the ratio of un-ionized drug concentrations between the
organic and aqueous phases, at equilibrium.
 C 
K O / W   oil  at equilibrium
 C water 
Generally, Octanol and chloroform are taken as the oil phase. IMP
Significance: Drug molecules having higher KO/W will cross the lipid cell membrane.

Dissolution
The dissolution rate of a drug substance in which surface area is constant during
disintegration is described by the modified Noyes-Whitney equation.
dc DA
 ( CS  C )
dt hV
Where, D = diffusion coefficient of the drug in the dissolution medium
h = thickness of the diffusion layer at the solid/liquid interface
A = surface area of drug exposed to dissolution medium.
V = volume of the medium
CS = Concentration of saturated solution of the solute in the dissolution medium at the
experimental temperature.
C = Concentration of drug in solution at time t.
When A = constant and CS >> C the equation can be rearranged to
dC DA V dC DA D
 CS or ,  CS or , W  k A t Where, k 
dt hV dt h h
where, W = weight (mg) of drug dissolved at time t
 mg  Slope = kA
k = intrinsic dissolution rate constant  2  W
 min cm 

time (t)

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Determination of k
 Pure drug powder is punched in a die and punch apparatus to give a uniform cylindrical
shape. The tablet is covered with wax in all sides. One circular face is exposed to the
dissolution medium. Thus, as dissolution proceeds, the area, A, remains constant.
 Time to time dissolution medium is taken out and fresh
medium added to the chamber.
 With two types of assembly, the experiments can be
carried out.
. ... ...
Stability analysis .. ... ....
Preformulation stability studies are the first quantitative Static disc Rotating disc
assessment of chemical stability of a new drug. This may dissolution dissolution
aparatus apparatus
involve
1. Stability study in toxicology formulation
2. Stability study in solution state
3. Stability study in solid state.

Stability study in toxicology formulation

A new drug is administered to animals through oral route either by
(i) mixing the drug in the feed
(ii) in the form of solution
(iii)in the form of suspension in aqueous vehicle
 Feed may contain water, vitamin, minerals (metal ions), enzymes and different functional
groups that may severely reduce the stability of the new drug. So stability study is should
be carried out in the feed and at laboratory temperature.
 For solution and suspension, the chemical stability at different temperature and pH should
be checked.
 For suspension-state the drug suspension is occasionally shaken to check dispersibility.
Solution stability
Objective: Identification of conditions necessary to form a stable solution.
Stability of a new drug may depend on:
(i) pH (ii) ionic strength (iii) co-solvent
(iv) light (v) temperature (vi) oxygen.

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pH stability study
(i) Experiiments to confirm decay at the extremes of pH and temperature. Three stability
studies are carried out at the following conditions
(a) 0.1N HCl solution at 900C
(b) Solution in water at 900C
(c) 0.1 N NaOH solution at 900C
These experiments are intentionally done to confirm the assay specificity and for maximum
rates of degradation.
(ii) Now aqueous buffers are used to produce solutions with wide range of pH values but with
constant levels of drug concentration, co-solvent and ionic strength.
All the rate constants (k) at a single temperature are then plotted as a function of pH.

(ii) Ionic strength

Since most pharmaceutical solutions are intended for parenteral routes of administration,
the pH-stability studies should be carried out at a constant ionic strength that is
compatible with body fluids. The ionic strength () of an isotonic 0.9%w/v sodium
chloride solution is 0.15.
Ionic strength for any buffer solution can be calculated by
1

2
 mi Z i
2
where, mi = molar concentration of the ion
Zi = valency of that ion
For computing,  all the ionic species of the buffer solution and drugs are also taken into
calculation.

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(iii) Co-solvents
Some drugs are not sufficiently soluble to give concentrations of analytical sensitivity. In
those cases co-solvents may be used. However, presence of co-solvents will influence the rate
constant. Hence, k values at different co-solvent concentrations are determined and plotted
against % of co-solvent. Finally, the line is extrapolated to 0% co-solvent to produce the
actual k value (i.e. in pure solvent).

(iv) Light
Drug solutions are kept in
(a) clear glass ampoules
(b) amber color glass container
(c) yellow-green color glass container
(d) container stored in card-board package or wrapped in aluminium foil – this one
acts as the control.
Now the stability studies are carried out in the above containers.

(v) Temperature
The rate constant (k) of degradation reaction of a drug varies with temperature according to
Arrhenius equation.
Ea
 Ea 1
k  Ae RT
or , ln  ln A   
R T 
where, k = rate constant Ea
Slope =
A = frequency factor ln k R
Ea = energy of activation
R = gas constant 1/ T
T = absolute temperature

Procedure
Buffer solutions were prepared and kept at different temperatures. Rate constants are
determined at each temperature and the ln k value is plotted against (1/T)).
Inference
 The relationship is linear  a constant decay mechanism over the temperature range
has occurred.

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 A broken or non-linear relationship  a change in the rate-limiting step of the

reaction or change in decay mechanism.

Uses
Shelf life of the drug may be calculated.
e.g. Time Concentration of drug remaining
0 100 %
t10% 90%
Therefore, ln C = ln C0 – k1t
Ln C/C0 = – k1t
90 ln 0.90 0.105
or, ln   k1t10% or, t10%  
100  k1 k1
where, t10% = time for 10% decay to occur if the reaction follows 1st order kinetics

Conclusion
If the drug is sufficiently stable, liquid formulation development may be started at once.
If the drug is unstable, further investigations may be necessary.

Solid state stability

Objectives
Identification of stable storage conditions for drug in the solid state and identification of
compatible excipients for a formulation.
Characteristics
Solid state reactions are much slower, so the rate of appearance of decay product is measured
(not the amount of drug remaining unchanged).
 To determine the mechanism of degradation thin layer chromatography (TLC),
fluorescence or UV / Visible spectroscopy may be required.
 To study polymorphic changes DSC or IR-spectroscopy is required.
 In case of surface discoloration due to oxidation or reaction with excipients, surface
reflectance equipment may be used.

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A sample scheme for determining the bulk stability profile of a new drug:

Storage condition 4 weeks 8 weeks 12 weeks

50C – Refrigerator
220C – Room Temperature
370C – Ambient humidity
370C / 75% RH (Relative Humidity)

Light box
Clear box
Amber glass
Yellow-Green glass
No exposure (Control:- Card-board box or wrapped with aluminium foil)
500C – Ambient Humidity
– O2 Head Space
– N2 Head Space
700C – Ambient Humidity
900C – Ambient Humidity

Procedure
1. Weighed samples are placed in open screw-capped vials are exposed to a variety of
temperatures, humidities and light intnesities. After the desired time samples are taken out
and measured by HPLC (5 – 10 mg), DSC (10 to 50mg), IR (2 to 20mg).
2. To test for surface oxidation samples are stored in large (25ml) vials for injection capped
with Teflon-lined rubber stopper. The stoppers are penetrated with needles and the
headspace is flooded with the desired gas. The resulting needle holes are sealed with wax
to prevent degassing.
3. After fixed time those samples are removed and analyzed.

Drug-excipient stability profile

Hypothetical dosage forms are prepared with various excipients and are exposed to various
conditions to study the interactions of drug and excipients.

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PHARM AROCKS GPAT SUCCESS TEST SERIES-2016 EM ULSION

EMULSION
Syllabus:
Definitions, general formulation of an emulsion and the components used in the formulation of emulsions with
examples: Emulsifying agents, oil phase ingredients, aqueous phase ingredients, preservatives, stabilizers,
coloring and flavouring agents and such other components processing and equipments on industrial scale. An
account of lotions, creams, collodions with the processing and equipment.

Questions:
Q.1 What are emulsions and emulsifying agents? Give examples. [8]
Q.2. Give any one method of formulation of emulsion and production on large scale with different additives. (98)
[8]
Q.3. Explain the different mechanical equipments those are at present available for emulsification. (96) [8]
Q.4. Discuss problems that may arise in production of emulsions. (96) [8]
Q.5. Write notes on auxiliary emulsifiers.

DEFINITION
An emulsion is a thermodynamically unstable dispersed system consisting of at least two immiscible liquid
phase, one of which is dispersed as globules in the other liquid phase.
The system is stabilized by the presence of an emulsifying agent.
Emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are
semisolid in nature.
The particle diameter of the dispersed phase generally extends from about 0.1 to 10 m and as 100 m are
not uncommon in some preparations.

TYPES OF EMULSIONS
(I) Ordinary emulsion systems / Primary emulsion systems / Simple emulsion systems
(i) o/w type  oil dispersed in water
oil  dispersed phase
water  continuous phase
(ii) w/o type  water dispersed in oil
water  dispersed phase
oil  continuous phase
(II) Special emulsion systems
(i) Multiple emulsions  w/o/w  type
o/w/o  type
(ii) Micro emulsion

Simple emulsion type:

o/w- type of emulsion is a system in which the oil is dispersed as droplet throughout the aqueous phase.
Most pharmaceutical emulsions designed for oral administration are of the o/w type; emulsified lotions and
creams either of o/w or w/o type depending on their use.
Certain foods such as butter and some salad creams are w/o type emulsions.
Multiple emulsion type
These multiple emulsions have been developed with a view to delay the release of an active ingredient. In
this type of emulsions three phases are present, i.e. the emulsion has the
form w/o/w or o/w/o. In these “emulsions within emulsions”, any drug
present in the innermost phase now has to cross two phase-boundaries to
reach the external continuous phase.
I : Continuous phase (External aqueous phase)
II: Middle oil phase
III: Inner aqueous phase

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Advantages of multiple emulsions

(i) Prolongation of drug action
(ii) Location of drug in the body.

Micro emulsions
Microemulsions are liquid dispersion of water and oil that are made homogeneous, transparent and stable by the
addition of relatively large amount of a surfactant and a co-surfactant. They appear to represent a state
intermediate between thermodynamically unstable emulsions and solubilized systems.
Unlike emulsions, they appear as clear transparent solution, but unlike solubilized systems micro-
emulsions may not be thermodynamically stable.
Microemulsions containing droplets (w/o or o/w types) with the globule size 10 to 200nm and the volume
fraction of the dispersed phase varies from 0.2 to 0.8.

DETERMINATION OF EMULSION TYPE

Several methods are commonly used to determine the type of emulsion. The types of emulsion determined
by one method should always be confirmed by means of second method.
(1) Dye solubility test
A small amount of a water soluble dye (e.g. methylene blue or brilliant blue) may be dusted on the surface of the
emulsion.
If water is the external phase (i.e. o/w type) then the dye will be dissolved uniformly throughout the
media.
If the emulsion is of the w/o -type then particles of dye will lie in clumps on the surface.
(2) Dilution test
This method involves dilution of the emulsion with water. If the emulsion mixes freely with the water, it
is of o/w -type. Generally, addition of disperse phase will crack an emulsion.
(3) Conductivity test
This test employs a pair of electrodes connected to an external electric source and immersed in the
emulsion. If the external phase is water, a current will pass through the emulsion and can be made to deflect a
volt-meter needle or cause a light in the circuit to glow. if the oil is the continuous phase then the emulsion will
fail to carry the current.
Methods for determination of emulsion type:
Test Observation Comments
1. Dilution test Emulsion can be diluted only with Useful for liquid emulsions only.
external phase.
2. Dye test Water-soluble solid dye tints only o/w May fail if ionic emulsifiers are
emulsion and reverse. Microscopic present.
observation usually is helpful.
3. Conductivity test Electric current is conducted by o/w Fails in nonionic o/w emulsions.
emulsions, owing to the presence of
ionic species in water.
4. Fluorescence test Since oils fluoresce under UV-light, Not always applicable
o/w emulsions exhibit dot pattern, w/o
emulsions fluoresce throughout.
5. CoCl2 / filter paper test Filter paper impregnated with CoCl2 May fail if emulsion is unstable or
and dried (blue) changes to pink when breaks in presence of electrolyte.
(o/w) emulsion is added.

FORMULATION OF EMULSION
In developing the formula of an emulsion the crucial decisions are related to the choice of the aqueous
and oil phases and of the emulgents and their relative proportions. There can be no general guideline in this
respect and the choice of phases and emulgents should be related to the qualities desired for the final product.
Usually, ingredient selection is made on the basis of the experience and personal tastes of the formulator and by
trial and error.

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CHEMICAL PARAMETERS
Chemical stability
All the ingredients of an emulsion should be chemically compatible.
e.g. a soap cannot be used as an emulsifier in a system having a final pH of less than 5.
e.g. some lipids are subjected to chemical changes due to oxidation (rancidity); so in general it is simpler
to avoid their use than to depend on antioxidants
Safety
All the ingredients should pass the toxicological tests. It is essential, therefore, for the formulator to
depend heavily on toxicologic information from suppliers or in the scientific literature, and on regulatory
activities by governmental agencies.
Choice of lipid phase
The choice of lipid phase depends on the ultimate use of the product.
(i) If the oily phase is the active-ingredient itself (e.g. liquid paraffin emulsion) the formulator has nothing to
choose from.
(ii) The drug in a pharmaceutical preparation should not be too soluble in lipid phase then it will reduce the rate
of transfer of the drug molecule to other phases.
(iii) Emulsions prepared for topical purpose (e.g. cosmetics and pharmaceutical emulsions) should possess a good
“feel”. Emulsions normally leave a residue of the oily components on the skin after the water has evaporated.
Therefore, the tactile characteristics of the combined oil phase are of great importance in determining
consumer acceptance of an emulsion
Phase - volume ratio
The ratio of the internal phase to the external phase is frequently determined by the solubility of the
active ingredients, which must provide the required dose.
If this is not the primary criteria, the phase ratio is normally determined by the desired consistency of the
product. For liquid emulsions the limits of internal phase vary from 40 to 60%, since with such amounts a stable
and acceptable emulsion can be prepared. Lower amounts of internal phase (i.e. disperse phase) gives a product
of low viscosity with pronounced degree of creaming while higher percentage may produce highly viscous
emulsions with tendency of phase inversion.

TABLE 1: Ingredients for oil-phase of emulsions

Class Identity Consistency
Hydrocarbon Mineral oils Fluids of varying viscosity
Hydrocarbon Petrolatum Semisolid
Hydrocarbon Polyethylene waxes Solids
Hydrocarbon Microcrystalline waxes Solids
Ester Vegetable oils Fluids of varying viscosity
Ester Animal fats Fluids or solids
Ester Lanolin Semisolid
Ester Synthetic (e.g. isopropyl myristate) Fluids
Alcohols Long chain (natural & synthetic) Fluids or solids
Fatty acids Long chain (natural & synthetic) Fluids or solids
Ethers Polyoxypropylene Fluids of varying viscosity
Silicones Substituted silicones Fluids of varying viscosity
Mixed Plant waxes (e.g. Candellia) Solid
Mixed Animal waxes (e.g. Beeswax) Solid
Choice of emulsifying agents / Emulsifiers / Emulgents
Emulsifying agents are broadly classified into three classes:
(i) Synthetic emulsifying agent / Surface active agents (SAA) / Surfactants
(ii) Hydrophilic colloid
(iii) Finely divided solids
When an emulsifier is used alone to stabilize an emulsion  it is called primary emulsifier. Some times a second
emulsifier is used to help the primary emulsifier in stabilizing the system  the second emulsifier is known as
auxiliary emulsifier. Generally emulsifiers from (ii) and (iii) category are used both as primary and auxiliary
emulsifier.

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A successful emulsifier must possess some or all of the following characteristics:

(a) The surface tension should be reduced to a value less than 10 dynes/cm2.
(b) A complete and coherent film should be formed around the dispersed globules so as to prevent their
coalescence.
(c) Should assist in building up the zeta potential and viscosity since both of these phenomena contribute to the
stability.
Choice of synthetic surface active agents / Surfactants:
Molecules and ions that are absorbed at interfaces are termed surface-active-agents
or surfactants. An alternative expression is amphiphile, which suggests that the molecule or
ion has a certain affinity for both polar and nonpolar solvents. Due to the amphiphilic nature
of surfactants they absorb at the oil-water interface.
Griffin devised an arbitrary scale of values to serve as a measure of the hydrophilic-
lipophilic balance (HLB) of surface-active -agents.

w/o emulsifiers o/w emulsifiers

0 3 6 9 12 15 18

Griffin’s HLB Scale

Mode of action of synthetic surfactants
This group of emulsifiers form a flexible film on the oil-water interface. They lower interfacial tension
markedly and this contribute to the stability of emulsion. In case of ionic surfactants surface charge is developed,
increasing the zeta-potential, which will cause repulsion between two adjacent globules.
e.g. Sodium lauryl sulphate
Polyoxyethylene sorbitan mono oleate (Polysorbate 80).
Classification of synthetic Surface Active Agents
Chemical formula (in aqs. soln.)
Lipophilic Surface
Class Surface Active Agent group Hydrophilic group inactive
ion
1. Anionic
(a) Alkali soap Potassium stearate C17H35 COO K+
(b) Organic Sodium lauryl sulphate C12H25 OSO3 Na+
sulphates (Sod. dodecyl sulphate)
(c) Organic Sodium cetyl sulphonate C16H33 SO3 Na+
sulphonates (Sod. hexadecane
sulfonate)

2. Cationic
(a) Quaternary Cetyl trimethyl C16H33 N+(CH3) 3 Br
ammonium ammonium bromide (or
compounds cetrimide)
(b) Pyridinium Dodecyl pyridinium C12H25 N+C5H5 Cl
compounds chloride

3. Ampholytic In alkaline soln. anionic

Amino acids N-dodecyl alanine C12H25 NH  CH2 CH2 COO Na+
In acid solution  cationic
C12H25 N+H2  CH2 CH2 COOH Cl
At isoelectric point  zwitterion
C12H25 N+H2  CH2 CH2 COO none

Chemical formula (in aqs. soln.)

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Lipophilic Surface
Class Surface Active Agent group Hydrophilic group inactive ion

4. Non-ionic
(a) Alcohol- Polyethylene glycol 1000 CH2(CH2)n (OCH2CH2)mCOO none
polyethylene monocetyl ether (n= 15 to 17) (m = 20 to 24)
glycol ethers (cetomacrogol 1000)
(b) Fatty acid- Polyethylene glycol 40 C17H33 CO(OCH2CH2)40OH none
polyethylene monostearate
glycol ethers
(c) Fatty acid- Sorbitan mono-oleate C17H33 COO CH2
O none
polyhydric (TWEEN)
HO OH
alcohol esters OH

O
Polyoxyethylene sorbitan C17H33 COO CH2 none
mono-oleate H(O CH2 CH2)nO O(CH2 CH2 O)nH
O(CH2 CH2 O)nH

The HLB number of surfactants may vary from 40 (sodium lauryl sulfate) to 1 (oleic acid). Emulsifying
agents, sometimes used singly, are preferably a combination of two emulsifying agents, which will give a
weighted HLB of 8 to 16 which is satisfactory for o/w emulsions and an HLB 3 to 8 for w/o emulsions.
NOTE: The HLB required for emulsifying a particular oil in water can be determined by trial and error method;
i.e. by preparing appropriate emulsions with emulsifiers having a range of HLB values and then determining that
HLB values that yields the “best emulsion”. That HLB value is named as Required HLB or RHLB”.
TABLE : REQUIRED HLB VALUE FOR SOME OIL PHASE INGREDIENTS
Oil RHLB for o/w RHLB for w/o
Cottonseed oil 6-7 
Petrolatum 8 
Beeswax 9-11 5
Paraffin wax 10 4
Mineral oil 10-12 5-6
Methyl silicone 11 
Lanolin, anhydrous 12-14 8
Carnauba wax 12-14 
Lauryl alcohol 14 
Castor oil 14 
Kerosene 12-14 
Cetyl alcohol 13-16 
Stearyl alcohol 15-16 
Carbon tetrachloride 16 
Lauric acid 16

Oleic acid 17

Stearic acid 17
Example: Formula of an emulsion is as follows:
Ingredient Amount RHLB (o/w)
1. Beeswax 15g 9
2. Lanolin 10g 12
3. Hard paraffin wax 20g 10
4. Cetyl alcohol 5g 15
5. Emulsifier 2g
6. Preservative 0.2g
7. Color q.s.
8. Water, purified q.s. 100g

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To calculate the overall RHLB of the emulsion the following calculation is carried out:
Oil Phase Amount (Amount/Total)xRHLB
1. Beeswax 15g (15/50)x9 = 2.7
2. Lanolin 10g (10/50)x12 = 2.4
3. Paraffin 20g (20/50)x10 = 4.0
4. Cetyl alcohol 5g (5/50)x15 = 1.5
Total 50g 10.6
Next, a blend of two emulsifiers is chosen, one with an HLB above 10.6 and the other below 10.6. Let these two
surfactants be Tween80 (HLB = 15) and Span 80 (HLB = 4.3). These two surfactants should be mixed in such a
ratio that the mixture will have a HLB of 10.6. By aligation method:
HLB of Tween80 Parts of Tween80 15 6.3
RHLB 10.6
HLB of Span80 Parts of Span80 4.3 5.6
Required amount of Tween80 = {6.3/(6.3+5.6)}x Total amount of emulsifier
= 0.53x2 g
= 1.06 g
Required amount of Span80 = {5.6/(6.3+5.6)}x Total amount of emulsifier
= 0.47x2 g
= 0.94 g
Therefore, using 1.06 g Tween80 and 0.94 g of Span 80 we can stabilize the above formula of an
emulsion.

Choice of hydrophilic colloids

The naturally occurring gums and synthetic hydrophilic polymers are used as either primarily or (mainly)
auxiliary emulsifiers.
Mode of action
(i) They do not reduce the surface tension but forms a rigid film on the oil droplets and form
a stable o/w emulsion  thus inhibits coalescence of droplets.
(ii) As an auxiliary emulsifier they increase the viscosity of the continuous phase so that
movement of dispersed phase is reduced.
Examples:
(i) Plant origin: Acacia, tragacanth, alginates, chondrus and pectin.
(ii) Animal source: Gelatin, egg yolk, casein, woolfat, cholesterol and lecithin.
(iii) Synthetic: Methyl cellulose, Hydroxyethyl cellulose, Polyoxyethylene polymer and Carboxyvinyl
polymer.
The natural gums exhibit some type of incompatibility or instability depending on the presence of various cations,
on pH, or on a second hydrophilic polymer.

Choice of finely divided solid particles

The compounds most frequently used in pharmacy are the colloidal clays: bentonite (aluminium silicate)
and veegum (magnesium aluminium silicate). They act as good emulsifiers, especially in combination with
surfactants or viscosity building agents.
Mode of action
(i) They tend to absorb at the oil-water-interface and form thick impenetrable
films.
(ii) Sometimes increases the viscosity of water (as continuous phase).
Generally finely divided solids are used in conjunction with a surfactant to prepare
o/w emulsions but both o/w and w/o preparations can be prepared by adding the
clay to the external phase first.
They are used frequently for external purposes such as lotion or cream.

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Specific formulation consideration: Consistency

Once the desired emulsion and emulsifiers have been chosen, a consistency that provides the desired
stability and yet has the appropriate flow characteristics must be attained.
The sedimentation or creaming rate of suspended spherical particles is inversely proportional to the
viscosity in accordance with Stoke’s law.
Since emulsions should flow or spread easily and since higher viscosity favors stability  so Thixotropy
in an emulsion is desirable (Thixotropy = phenomenon in which the viscosity of a preparation is reduced by
agitation but increases after agitation has been stopped.
Viscosity of emulsions responds to the following changes:
1. When the viscosity of the continuous phase is increased the viscosity of emulsion is also increased.
o/w emulsion: Viscosity of water is increased by using gums, clays and viscosity building agents.
w/o emulsion: Viscosity of oil is increased by addition of polyvalent metal soaps or the use of high
melting waxes and resins.
2. The greater the volume of internal phase, (i.e. greater phase volume ratio) the greater is the apparent
viscosity.
3. The viscosity and stability of an emulsion is increased by reducing the size of droplets and by formation of
floccules or clumps.
4. It is routinely observed that viscosity of emulsions increases upon aging. Hence, it is recommended that a
newly formulated emulsion be allowed to rest undisturbed for 24 hours before checking its viscosity.

Choice of an antimicrobial preservative

Sources of contamination:
(i) Contaminated raw materials
(ii) Poor sanitation during preparation
(iii) Contamination by the end users
Substrates of contamination:
(i) Mainly the water phase is a good medium for microbial growth.
(ii) Some ingredients, such as carbohydrates, pectin, proteins, sterols, and phosphates readily supports the
growth of a variety of microorganisms.
Remedies:
(i) Use of uncontaminated raw materials
(ii) Careful and through cleaning of equipment with steam.
(iii) Addition of preservatives
Preservatives commonly used:
Chlorocresol, chlorobutanol, mercurials [e.g. phenyl mercuric nitrate (PMN), phenyl mercuric acetate
(PMA), esters of parahydroxy benzoate (methyl, propyl, butyl, benzyl paraben), sodium benzoate, sorbic acid
etc.
[For more details see Lieberman & Lachman, Industrial Pharmacy, 3rd Edn. pp 521.]
Since microorganisms can reside in the water or the lipid phase or both, the preservative should be
available at an effective level in both phases. So it is advisable to add an oil soluble and an water soluble
preservative simultaneously.
A good example is methyl and propyl paraben. In this case methyl paraben is soluble in water while propyl and
higher esters are almost water-insoluble.
Preservatives sometimes interact with some ingredients. e.g. phenolic preservatives are especially
susceptible to interaction with compounds containing polyoxyethylene groups. Sometimes preservatives are
solubilized by the surfactants. The bound or complexed or solubilized preservative can not act as preservative.

Choice of antioxidants
The inclusion of an antioxidant in an emulsion formulation may be necessary to protect, not only an
active ingredient but also formulation components (e.g. unsaturated lipids) which are oxygen labile.
Oxidation occurs spontaneously under mild conditions generally involved some free radical reactions.
Kinetic measurements of fat oxidation in o/w emulsions indicate that the rate of oxidation is dependent on
(i) the rate of oxygen diffusion in the system,
(ii) oxygen pressure (i.e. oxygen content)

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(iii) trace element of metal such as Cu, Mn, or Fe or their ions may catalyze the oxidative reactions. Thus the use
of chelating agents, in a formulation may markedly improve product stability.
(iv) Some oxidative degradation is pH dependent. So the pH stability profile of the drug and of protective
formulation should be established during product development.

List of selected antioxidants for emulsion system:

1. Chelating agents e.g. Citric acid
EDTA (Ethylene diamine tetraacetic acid)
Phenyl alanine
Phosphoric acid (H3PO4)
Tartaric acid
2. Preferentially oxidized compounds (Reducing agents)
e.g. Ascorbic acid
Sodium sulphite (Na2SO3)
Sodium bisulfite (NaHSO3)
Sodium metabisulfite (Na2S2O5)
3. Chain terminators
Water soluble compounds e.g. Cystine hydrochloride
Thioglycerol
Thioglycollic acid
Thiosorbitol
Lipid soluble compounds e.g. Alkyl gallates (octyl, propyl, dodecyl)
Butylated hydroxy toluene (BHT)
Butylated hydroxy anisole (BHA)
-tocopherol (Vit-E)
Hydroquinone
Deaeration
The formulator may wish to deaerate the system by :
(i) bubbling N2 gas through the liquids to remove dissolved O2.
(ii) boiled before use
(iii) exposure to vacuum during ultrasonic agitation
(iv) the end space above the container can be flushed with N2 just before sealing.

Reducing agents: e.g. Ascorbic acid (Vit-C)

Sulphites etc.
They preferentially get oxidized before the oxidation of oil takes place.

Uses:
(i) BHA, BHT, Vit-E and the alkyl gallates are particularly popular in pharmaceuticals and cosmetics.
(ii) BHA and BHT have a pronounced odour and should be added at low concentration.
(iii) Alkyl gallates have a better taste.
(iv) L-tocopherol (Vit-E) is well suited for edible or oral preparations, such as those containing Vitamin A.
(v) Some trace metals like copper, iron, manganese ions catalyze the auto-oxidation reaction; therefore, a small
amount of sequestering agents like citric acid, EDTA, tartaric or phosphoric acid reduce the reaction rate.

PREPARATION

 After the purpose of the emulsions has been determined, i.e oral or topical use,
 and the type of emulsions, o/w or w/o,
 and appropriate ingredients selected
 and the theory of emulsification considered
Experimental formulations may be prepared by a method suggested by Griffin.

Experimental method
1. Group the ingredients on the basis of their solubilities in the aqueous and nonaqueous phase.
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2. Determine the type of emulsion required and calculate an approximate HLB value
3. Blend a low HLB emulsifier and a high HLB emulsifier to the calculated value
[N.B. For experimental formulations, use a higher concentration of emulsifier (e.g. 10 to 30% of the oil
phase) than that required to produce a satisfactory product.
4. Dissolve the oil-soluble ingredients and the emulsifiers in the oil. Heat, if necessary, to approximately 5 to
100C over the melting point of the highest melting ingredient of to a maximum temperature of 70 to 800C.
5. Dissolve the water-soluble ingredients (except acids and salts) in a sufficient quantity of water. Heat the
aqueous phase to a temperature which is 3 to 50C higher than that of the oil phase.
6. Add the aqueous phase to the oily phase with suitable agitation.
7. If acids or salts are employed, dissolve them in water and add the solution to the cold emulsion.
8. Examine the emulsion and make adjustments in the formulation if the product is unstable.

Large scale industrial method

The preparation of an emulsion requires work to reduce the internal phase into small droplets and
disperse them throughout the external phase. This can be accomplished by a mortar and pestle or a high speed
emulsifier. The addition of emulsifying agents not only reduces this work but also stabilizes the final emulsion.
Emulsions may be prepared by four principle methods:
1. Addition of internal phase to external phase
Let us take a model of o/w emulsion.
(i) The water soluble substances are dissolved in water and the oil soluble substances are dissolved in oil.
(ii) The oil mixture is added in portions to the aqueous preparation with agitation (in a colloid mill or
homogenizer).
N.B. Sometimes, in order to give a better shearing action during the preparation, all of the water is not mixed
with the emulsifying agent until the primary emulsion with oil is formed; subsequently, the remainder of the
water is added.
e.g. Emulsion using Gelatin-type A as the emulsifier.
Gelatin (Type A) 8g
Tartaric acid 0.6g
Flavour as desired
Alcohol 60ml
Oil 500ml
Purified water, to make 1000ml
Procedure
(i) The gelatin & tartaric acid are added to approximately 300ml water, allowed to stand for few minutes, heated
until gelatin is dissolve, then temperature is raised to 980C and this temperature is maintained for about 20
minutes. Cooled to 500C, flavor and alcohol are added and more water was added to make 500 ml.
(ii) The oil is added to the aqueous phase (i.e. external phase), and the mixture is agitated thoroughly and passed
it through a homogenizer or colloid mill.
2. Addition of the external phase to the internal phase
Let us take a model of o/w emulsion.
In this method water (external phase) is first added slowly to the oil (internal phase) to promote the formation of a
more w/o emulsion due to the presence of more oil than water. After further addition of water phase inversion to
an o/w emulsion should take place.
This method is especially successful when hydrophilic agents such as acacia, tragacanth or methyl
cellulose are first mixed with oil, effecting dispersion without wetting. Water is added and, eventually, an o/w
emulsion is formed.
e.g. Mineral oil emulsion
Mineral oil 500ml
Acacia, in very fine water 125g
Syrup 100ml
Vanillin 40mg
Alcohol 60ml
Purified water, upto 1000ml
(i) The mineral oil and acacia are mixed in a dry mortar. Purified water, 250 ml (Phase volume ratio o/w = 2: 1)
is added and the mixture triturated vigorously until an emulsion is formed.
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(ii) A mixture of the syrup, 50 ml of purified water and the vanillin dissolved in alcohol are added in divided
portions with trituration
(iii) Sufficient purified water is then added to the proper volume, the mixture well and homogenized.

3. Mixing both phases after warming each

This method is use when waxes or other substances which require melting are used. The oil-soluble
emulsifying agents, oils and waxes are melted and mixed thoroughly. The water-soluble ingredients dissolved in
the water and warmed to a temperature slightly higher than the oil phase.
The oil phases are then mixed and stirred until cold. For convenience, but not necessity, the aqueous
solution is added to the oil mixture.
This method frequently is used in the preparation of ointments and creams.
e.g. An oral emulsion (o/w) containing an insoluble drug
1. Cotton seed oil 460g
2. Sulphadiazine 200g
3. Sorbitan monostearate 84g
4. Polyoxyethylene 20 sorbitan mono stearate 36g
5. Sodium benzoate 2g
6. Sweetener q.s.
7. Purified water 1000g
8. Flavor oil q.s.
Procedure
(i) Heat the first three ingredients to 500C and pass through colloid mill.
(ii) Add the next four ingredients at 500C to the first three ingredients at 650C and stirred while cooling to 450C.
(iii) Add the flavor oil and continue stirring until room temperature is reached.

4. Alternate addition of the two phases to the emulsifying agent

Model: Let us prepare an o/w type of emulsion.
(i) A portion of the oil is added to all of the oil-soluble emulsifying agents with mixing.
(ii) Equal quantity of water is added to all of the water-soluble emulsifying agents with mixing.
(iii) Aqueous solution is mixed with oil phase stirred until the emulsion is formed.
(iv) Further portions of water and oil are added alternately until the final product is formed.
N.B. The high concentration of the emulsifying agent in the original emulsions makes the initial emulsification
more likely and the high viscosity provides effective shearing actin leading to small droplets in the emulsion.
This method is often used successfully with soaps.

EQUIPMENTS
 The preparation of emulsion requires certain amount of energy to form the interface between the two phases,
and additional work must be done to stir the system to overcome the resistance to flow.
 In addition, heat often is supplied to the system to melt waxy solids and /or reduce the viscosity of the oil
phase.
Because of the variety of oils used, emulsifying agents, phase-volume ratio and the desired physical properties of
the product, a wide selection of equipment is available for preparing emulsions.

1. Mortar and pestle

It consists of a glass or porcelain mortar and a pestle.
Advantages:
(i) Small quantity emulsions can be prepared in the laboratory.
(ii) Low cost
(iii) Simplest operation among all other instruments.
Disadvantages
(i) Generally, the final particle size is considerable larger then in other equipments.
(ii) It is necessary for the ingredients to have a certain viscosity prior to trituration in order to achieve a
satisfactory shear.

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2. Agitators / Mechanical stirrers

An emulsion may be stirred by means of various impellers (propellers:
produce axial movements; turbines produce radial and tangential movements)
mounted on shafts, which are placed directly into the system to be emulsified.
For low viscosity emulsions propeller type can be used but for higher viscosity
turbine type is used.
The degree of agitation is controlled by the rotational speed of impeller,
by the patterns of the liquid flow and the resultant efficiency of mixing are
controlled by the type of impeller, its position in the container, the presence of baffles, and the general shape of
the container.
Advantages:
(i) Agitators are used particularly for the emulsification of easily dispersed, low-viscosity oils.
(ii) Can be used for small-scale production and laboratory purpose.
Disadvantages:
Continuous shaking tends to break up not only the phase to be dispersed but also the dispersion medium, in this
way, impairs the ease of emulsification.

3. Colloid mill GRINDING

The principle of operation of the colloid mill is SURFACES
the passage of the mixed phases of an emulsion
formula between a stator and a high speed rotor FEED
revolving at speeds of 2000 to 18,000 rpm. ROTOR
The clearance between the rotor and the stator is
adjustable, usually from 0.001 inch upward. The
emulsion mixture, while passing between the
rotor and the stator, is subjected to a STATOR
tremendous shearing action which effects a fine
dispersion of uniform size. COOLANT
The shearing forces applied in the colloid mill OUTLET
usually raises the temperature within the COOLANT
COOLANT
emulsion. Hence, a coolant is used to absorb the INLET
excess heat.
Advantage
(i) Very high shearing force can be generated.
(ii) Very fine particles can be prepared. OUTLET
(iii) Particularly useful in preparing suspensions containing poorly wetted solids.
(iv) Useful for the preparation of relatively viscous emulsions.

4. Homogenizers
Impeller type of equipment frequently produce a satisfactory emulsion; however, for further reduction in particle
size, homogenizers may be employed.
Homogenizers may be used in one of two ways:
(i) The ingredients in the emulsion are mixed and then passed HOMOGENIZED
through the homogenizer to produce the final product. PRODUCT
(ii) A coarse emulsion is prepared in some other way and then
passed through a homogenizer for the purpose of decreasing
the particle size and obtaining a greater degree of VALVE
uniformity and stability. SEAT
The coarse emulsion (basic product) enters the valve seat at BASIC