Short Answer questions (2 marks)

1. Define controlled drug delivery systems with examples.

Controlled Release : It includes any drug delivery system from which the drug is delivered at a predetermined rate
over a prolong period of time.
 The primary objectives of controlled drug delivery are to ensure safety and to improve efficacy of drugs as
well as patient compliance.
 Examples include transdermal patches, implantable pumps, and intramuscular depot injections.

2. Differentiate between controlled and sustained drug delivery system.

Sustained Release Dosage Form Controlled Release Dosage Form

1. The term sustained release has been constantly used 1. The term has a meaning that goes beyond the scope
to describe a pharmaceutical dosage form formulated to of sustained drug action.
retard the release of a therapeutic agent.
2. Constitutes dosage form that provides medication
2. Constitutes dosage form that maintains constant
over extended period of time. drug levels in blood or tissue.
3. SRDF generally do not attain zero order release
3. Maintains constant drug levels in the blood target
kinetics. tissue usually by releasing the drug in a zero order
pattern.
4. Usually do not contain mechanisms to promote 4. Controlled dosage forms contain methods to
localization of the drug at active site. promote localization of the drug at active site.

3. Give advantages of controlled drug delivery systems.

Advantages of Controlled Drug Delivery
1. Maintenance of drug levels within a desired range.
2. Less dosing and increased patient compliance.
3. Eliminate overdosing or underdosing.
4. Prevention of side effects.
5. Reduction in health care cost.
6. Improved efficiency in treatment.
7. Reduction in adverse side effects and improvement in tolerability.

4. What is rationale behind controlled drug delivery systems?

Rationale of Controlled Drug Delivery : The basic rationale of controlled drug delivery is to alter the
pharmacokinetics and pharmacodynamics of pharmacologically active moieties by using novel drug delivery
systems or by modifying the molecular structure and/or physiological parameters inherent in a selected route of
administration.
The primary objectives of controlled drug delivery are to ensure safety and to improve efficacy of
drugs as well as patient compliance. For conventional dosage forms only the dose and dosing interval can vary and
for each drug, there exists a therapeutic window of plasma concentration below which therapeutic effect is
insufficient and above which undesirable or toxic side effects are elicited. This is often defined as, "the ratio of
median lethal dose (LD50) to median effective dose (ED50)".

5. How will you select drug candidate for controlled drug delivery systems?
1. Most of the active pharmaceutical moiety (API) are weakly acidic or basic in nature that affect the water
solubility of API.
2. Weak water-soluble drugs are difficult to design the controlled release formulations.
3. High aqueous solubility drug show burst release followed by a rapid increment in plasma drug
concentration.
4. These types of drugs are a good candidate for CRDDS.
5. The pH dependent solubility also creates a problem in formulating CRDDS.
6. BCS class-III and IV drugs are not a suitable candidate for this type of formulations.

6. How absorption of drug affects design of controlled drug delivery systems?

Absorption: Uniformity in rate and extent of absorption is an important factor in formulating the CRDDS.
 However, the rate limiting step is drug release from the dosage form.
 The absorption rate should rapid the release rate to prevent the dose dumping.
 The various factors like; aqueous solubility, log P, acid hydrolysis, which affect the absorption of drugs.
 7. What is mean by reservoir and matrix system?
1. Reservoir Devices : Reservoir devices are characterized by a core of drug, the reservoir, surrounded by a
polymeric membrane.
 The nature of the membrane determines the rate of release of drug from the system.
 The advantages of reservoir diffusional systems are, zero-order delivery are possible and release rate will
vary with polymer type.
 The disadvantages of reservoir diffusional systems are, system must be physically plant site, difficult to
deliver high-molecular weight compounds, rupture can result in dangerous dose dumping.
2. Matrix Devices : A matrix device consists of drug dispersed homogeneously throughout a polymer matrix.
 In this model, drug in the outside layer exposed to the bathing solution is dissolved first and then diffuses
out of the matrix.
 This process continues with the interface between the bathing solution and the solid drug moving towards
the interior.
 Obviously, for this system to be diffusion controlled, the rate of dissolution of drug particles within the
matrix must be much faster than the diffusion rate of dissolved drug leaving the matrix.

8. What is mean by erosion and name two polymers used in erosion type controlled drug delivery formulations?
Erosion is defined as the physical dissolution of a polymer as a result of its degradation. Most biodegradable
polymers used for drug delivery are degraded by hydrolysis.
Ex. Poly (lactic acid), poly (lactic-co-glycolic acid), polyanhydrides, poly (ortho esters), poly (phosphoesters).

9. How the half-life and protein binding influence the design of controlled drug delivery systems?
1) Protein Binding : The drug-protein complex act as a reservoir in plasma for the drug.
 Drugs showing high plasma protein binding are not a good candidate for CRDDS because the protein
binding increases the biological half-life. So, there is no need to sustain the drug release.
This complex leads to :
i.Inhibition of therapeutic effect of such amount.
ii.Half-life is increased (compared to in vitro studies).
iii.Toxicity profiles elevated.
 Thus, in most of the cases, protein binding is undesirable.
 Many drugs are highly protein bound (may be 95%), thus the need of formulating a modified drug or drug
delivery system starts.
2) Biological half-life (t1/2) : In general, the drug having short half-life requires frequent dosing and suitable
candidate for controlled release system.
 A drug with long half-life requires dosing after a long-time interval.
 Ideally, the drugs having t1/2 2-3 hours, are a suitable candidate for CRDDS.
 Drugs having t1/2 more than 7-8 hours are not used for controlled release system.

10.Define core and coat materials with respect to microencapsulation.

(a) Core material : The solid core can be mixture of active constituents, stabilizers, diluents, excipients and
release-rate retardants or accelerators.
(b) Coat or wall or shell material : Compatible, non-reactive with core material. Provide desired coating
properties like; strength, flexibility, impermeability, optical properties, non - hygroscopicity, tasteless and stable.

11.Define microencapsulation and give its advantages.

 Microencapsulation may be defined as, "the process of surrounding or enveloping one substance within
another substance on a very small scale, yielding capsules ranging from less than one micron to several hundred
microns in size".
 It is mean of applying thin coating to small particle of solid or droplet of liquid and dispersion.
Advantages
1. Microspheres received much attention for targeting of anticancer drugs to the tumor.
2. They could be injected into the body due to the spherical shape and smaller size.
3. Better drug utilization will improve the bioavailability and reduce the incidence or intensity of adverse effects.
4. Reduces the dosing frequency and thereby improve the patient compliance.
 12.Write applications of microencapsulation.
Application Markets of Micro- Encapsulation
1) Food
2) Feed
3) Medicine
4) Veterinary
5) Household & personal care
6) Biotech
7) Pharmaceutical
8) Chemical industry
9) Agriculture
10) Waste treatment
11) Textile
12) Photography
13) Graphics & Printing
14) Electronics

13.Give classification of methods of microencapsulation.

Microencapsulation Techniques
I.Physical or physico-mechanical
1) Air suspension
2) Centrifugal extrusion
3) Pan coating
4) Spray-drying
a) Co-current
b) Counter-current
c) Mixed-flow
5) Vibrational nozzle
II.Physico-chemical
1) Ionotropic gelation
2) Coacervation
III.Chemical
1) Solvent Evaporation
2) Polymerization
a) Interfacial polymer
b) In-situ polymerization
c) Matrix polymer
3) Multiorifice certifungal

14.What is mean by mucoadhesion and give four examples of mucoadhesive polymers?

Mucoadhesion : The term "mucoadhesion" was coined for the adhesion of the polymers with the surface of the
mucosal layer. Bio adhesions are a phenomenon in which two materials at least one of which is biological and are
held together by means of interfacial forces.
Examples
1. Water
2. Glycoprotein and Lipids
3. Mineral salts
4. Free proteins

15.How membrane coating granules affects transmucosal permeation of drug?

I. Membrane coating granules can have a significant impact on the transmucosal permeation of drugs.
II. Transmucosal drug delivery involves the administration of medications through mucous membranes, such as
those found in the oral, nasal, buccal (cheek), rectal, vaginal, or ocular routes.
III. The goal of using membrane coating granules in transmucosal drug delivery is to enhance drug absorption and
bioavailability, improve patient compliance, and potentially avoid first-pass metabolism by the liver.
IV. It's important to note that the success of using membrane coating granules in transmucosal drug delivery
depends on various factors, including the properties of the drug, the characteristics of the mucosa at the site of
administration, and the specific design of the coating granules.
V. Therefore, the development and optimization of membrane coating granules require careful consideration and
experimentation to achieve the desired therapeutic outcomes.
16.What is mean by implant and give its two examples?
Implant : A substance or object that is put in the body as a prosthesis, or for treatment or diagnosis.
Ex. breast implant, nose prosthesis, ocular prosthesis, and injectable filler.

17.Enlist components of transdermal drug delivery?

Basic Components of TDDS
a) Polymer matrix/drug reservoir
b) Membrane
c) Drug
d) Permeation enhancers
e) Pressure-sensitive adhesives (PSA)
f) Backing laminates
g) Release liner
h) Other excipients like plasticizers and solvents

18.How the drug is permeated through skin?

 In the process of percutaneous permeation, a drug molecule may pass through the epidermis itself or may
get diffuse through shunts, particularly those offered by the relatively widely distributed hair follicles and eccrine
glands.
 In the initial transient diffusion stage, drug molecules may penetrate the skin along the hair follicles or
sweat ducts and then absorbed through the follicular epithelium and the sebaceous glands.
 When a steady state has been reached, the diffusion through the intact Stratum corneum becomes he
primary pathway for transdermal permeation.
 For any molecules applied to the skin, two main routes of skin permeation can defined:
a) Transepidermal route
b) Transfollicular route

19.What is mean by nasal and pulmonary drug delivery system?

Nasal drug delivery : This has been practiced for thousands of years, has been given a new lease of life. It is a
useful delivery method for drugs that are active in low doses and show no minimal oral bioavailability such as;
proteins and peptides. One of the reasons for the low degree of absorption of peptides and proteins via the nasal
route is rapid movement away from the absorption site in the nasal cavity due to the mucociliary clearance
mechanism.
Pulmonary Drug Delivery : The respiratory tract is one of the oldest routes used for the administration of drugs.
Over the past decades, inhalation therapy has established itself a valuable tool in the local therapy of pulmonary
diseases such as; asthma and COPD (Chronic Obstructive Pulmonary Disease). This type of drug application in the
therapy of these disease is a clear form of targeted drug delivery.

20.Differentiate between liposomes and niosomes.

Liposomes Niosomes
A naturally occurring type of vesicles A type of synthetic vesicles
Comparatively large (10- 3000 nm) vesicles Smaller (10-100 nm) vesicles
Consist of a phospholipid bilayer Consist of non-ionic surfactant of the alkyl or dialkyl
polyglycerol ether class
The primary type of phospholipid is Span 20, 40, 60, 80, 85 and Tween 20, 40, 60, 80 can
phosphatidylcholine be found
The phospholipid molecules contain two tails The non-ionic surfactants contain a single tail.
21.How nanoparticles are used as targeted drug delivery systems?
1. Intracellular targeting: They target reticuloendothelial systems for intracellular infections. For e.g. Ampicillin
loaded polyhexylcyanoacrylate (PIHCA) nanoparticles for salmonellosis.
2. Nanoparticles in chemotherapy: It acts as a carrier for anti-tumor agents:
 Chemoembolization: The approach here is, use of biodegradable particles administration to liver tumors
using catheter that passes directly into an artery of the tumor.
 Avoidance of Multidrug Resistance: This is the main failure of the Chemotherapeutic agents.
Nanoparticle loaded drugs has resulted in the effective treatment of a number of chemotherapy refractory cancers in
both animals and clinical models.
 Delivery of Anticancer Drugs: The polyalkyl cyanoacrylate Nanoparticles are possible means for
targeting to specific sites in the body. The small colloidal carriers are biodegradable and drug substances can be
incorporated normally by Surface adsorption. For e.g. Doxorubicinin polyalkylcyanoacrylate Nanoparticles.

22.Write advantages and disadvantages of targeted drug delivery systems.

Advantages of TDDS
1. Toxicity reduced, decrease harmful system effect.
2. Drugs smaller dose gives desired effect.
3. Avoidance of first pass metabolism.
4. Increase absorption of large molecules as peptides and particulates.
Disadvantages of TDDS
1. Requires highly sophisticated technology for formulations.
2. Requires skill for manufacturing.
3. Drug deposition at targeted sites may produce toxic symptoms.
4. High cost of formulation.

23.Enlist different approaches of targeted drug delivery system.

There are mainly two approaches :
(a) Chemical modification of the parent compound to a derivative which is activated only at the target site.
(b) Utilization of carriers such as; liposomes, microspheres, nanoparticles, monoclonal antibodies, cellular carriers
(erythrocytes and lymphocytes), macromolecules, platelets to direct the drug at its site of action.
(i) Prodrug approach
(ii) Chemical delivery approach
(iii) More approaches
 Active targeting (ligand mediated targeting).
 Passive targeting (natural targeting).
 Physical targeting.
 Chemical targeting.

24.Enumerate the different types of ocular dosage forms.

Classification of Inserts
1. Non-Erodible Inserts
(a) Ocusert
(b) Contact Lens
2. Erodible Inserts
(a) Lacriserts
(b) SODI
(c) Mindisc

25.What are an ideal requirements for ocular drug delivery systems?

IDEAL CHARACTERISTICS OF OCULAR DRUG DELIVERY SYSTEM
1. It should be sterile.
2. It should be isotonic to body fluids.
3. Buffer/pH adjustment.
4. Less drainage tendency.
5. Minimum protein binding.
26.Enlist intra ocular barriers.
1. Anatomical Barriers:
2. Physiological Barriers:
3. Blood Ocular Barrier:
4. Drug and Dosage Form Related Factors:
(a) Solubility
(b) Lipophilicity
(c) Molecular size and weight

27.List out various coating materials used for microencapsulations.

Composition of Coating:
1. Inert polymer.
2. Plasticizer.
3. Colouring agent.
4. Resins, waxes and lipids.
5. Release rate enhancers or retardants.

28.How will you differentiate bioadhesion and mucoadhesion?

29.What is composition of mucus layer?
In general, mucus is mainly composed of water (~95% w/w), mucins (~0.2 to 5.0% w/v), globular proteins (~0.5%
w/v), salts (~0.5 to 1.0% w/w), lipids (1–2% w/w), DNA, cells, and cellular debris

30.What is mean by penetration enhancer? Give its examples.

 Majority of drugs will not permeate into skin for therapeutic use.
 Some enhancers are used for synergistic action without showing its properties.
 E.g. dimethyl sulphoxide, acetone, propylene glycol and tetradihydrofuryl alcohol.

31.What is mean by gastric residence time and gastric emptying time?

Gastric Residence Time : The presence or absence of food in the stomach influences the gastric retention time of
the system. The presence of food increases the retention time and increases the absorption of the active agent by
allowing it to stay at the absorption site for a longer time.
Gastric Emptying Time : It is a test that measures the time it takes for food to empty from the stomach and enter
the small intestine. The test often is used to find out why your child is vomiting, having stomach pain or not
gaining weight. The test can be done as an inpatient or outpatient.

32.Enlist various approaches for gastroretention.

Approaches for GRDDS
1. Floating drug delivery systems.
2. Mucoadhesive systems.
3. Swellable systems.
4. High density systems.

33.Give applications of gastroretentive drug delivery system.

APPLICATIONS OF GASTROADHESIVE SYSTEMS
1. Enhanced Bioavailability : The bioavailability of riboflavin GRDF is significantly enhanced in comparison to
the administration of non-GRDF polymeric formulations.
2. Sustained Drug Delivery/Reduced Frequency of Dosing :This feature is associated with improved patient
compliance and thereby improves therapy.
3. Targeted Therapy for Local Ailments in the Upper GIT : The prolonged and sustained administration of the
drug from GRDF to the stomach may be advantageous for local therapy in the stomach and small intestine.
4. Reduced Fluctuations of Drug Concentration : Continuous input of the drug following GRDF administration
produces blood drug concentrations within a narrower range compared to the immediate release dosage forms.
34.What is difference between homopolymer and copolymer?

Homopolymers Copolymers
Homopolymers are formed through addition Copolymers are formed through condensation
polymerization polymerization
Consist of single species of repeating units Consist of two or more type of repeating units
Have a single type of monomer Have two or more types of monomers
Often have a simple structure Have a complex structure
Examples include PVC, polyethylene, polypropylene, Examples include poly (vinyl acetate), poly (ethylene
polystyrene, etc. oxide), etc.

35.What is mean by natural and synthetic polymer? Give its examples.

1. Natural polymers: These are derived from natural sources and can be polysaccharides and protein in chemical
nature.
For example: Albumin, Cellulose, Starch, Rubber, Wool.
2. Synthetic polymers: Synthetic polymers are of artificial origin which consist of fibers. This is the polymer,
which was prepared by Laboratory is known as Synthetic Polymer.
For example: Buna-S, Buna-R, Nylon, Polythene, Polyester.

36.How crystallinity of polymer affects drug release?

37.How will you classify polymers?

Classification of Polymers
A. Based on origin of source
1. Natural polymers
2. Semi-synthetic polymer
3. Synthetic polymers
B. Based on structure
1. Linear polymers
2. Branched chain polymers
3. Cross-linked polymers
C. Based on molecular forces
1. Elastomers
2. Fibers
3. Thermoplastics
4. Thermosetting polymers
D. Based on mode of polymerization
1. Addition polymers
2. Condensation polymers

38.What is method of preliminary study of ocular formulation?

39.Give examples of mediated IUDs?
Medicated IUDs: These are capable of delivering pharmacologically active antifertility agents.
For e.g. Copper bearing IUDs, Progesterone releasing IUD.
There are two types of medicated IUDs:
1. Copper bearing IUDs.
2. Hormone releasing IUDs: There are two types:
(a) Progesterone releasing IUD - Progestasert.
(b) Levonorgesterone IUD - Levonorgestrel releasing device - [MIRENA].
40.What are the types of IUDs?
Types of IUDs : 1. Non-medicated IUDs 2. Medicated IUDS
1. Non-medicated IUDs: These exert their contraceptive action by producing a sterile inflammatory response in
the Endometrium by its mechanical interaction. These do not contain any therapeutic effect. For e.g. Ring-Shaped
IUDs of Stainless Steel, Plastic IUDs, Lippes Loop, Dalkon Shield, Saf-T-Coil.
2. Medicated IUDs: These are capable of delivering pharmacologically active antifertility agents. For e.g. Copper
bearing IUDs, Progesterone releasing IUD.
There are two types of medicated IUDs:
I. Copper bearing IUDs.
II. Hormone releasing IUDS:
There are two types:
(a) Progesterone releasing IUD - Progestasert.
(b) Levonorgesterone IUD - Levonorgestrel releasing device - [MIRENA].

41.Give advantages of IUDs.

Advantages of IUD's
1. It can be used by almost any woman including nulliparous.
2. Its action lasts for ten years if it is not removed inbetween.
3. The onset of action is immediate.
4. It is suitable for lactating women.
5. Fertility returns promptly on discontinuation.
6. It can be used by women who are on any type of medication.
7. It is not associated with cancer of any organ unlike hormonal contraception.
8. It is cost effective.

42.Enlist the methods of liposome preparation.

Method of Preparation
I. Passive Loading Technique:
1. Mechanical Dispersion:
(a) Lipid hydration method:
(b) Micro emulsification:
(c) Sonication:
(d) French pressure cell method:
(e) Membrane extrusion:
(f) Dried reconstituted vesicles:
(g) Freeze-Thaw Method:
2. Solvent Dispersion:
(a) Ethanol Injection Method:
(b) Ether Infusion Method:
(c) Double emulsification:
(d) Reverse-phase evaporation:
3. Detergent Removal:
II. Active Loading Technique:
(a) Proliposome:
(b) Lyophilization:

43.Enlist formulation approaches of TDDS.

There are mainly two approaches :
(a) Chemical modification of the parent compound to a derivative which is activated only at the target site.
(b) Utilization of carriers such as; liposomes, microspheres, nanoparticles, monoclonal antibodies, cellular carriers
(erythrocytes and lymphocytes), macromolecules, platelets to direct the drug at its site of action.
(i) Prodrug approach
(ii) Chemical delivery approach
(iii) More approaches
 Active targeting (ligand mediated targeting).
 Passive targeting (natural targeting).
 Physical targeting.
 Chemical targeting.
44.What are the applications of monoclonal antibodies?
Applications of Monoclonal Antibodies
1. Diagnostic Applications
(a) Biochemical analysis
(b) Diagnostic imaging
2. Therapeutic Applications
(a) Direct use of mAB's as therapeutic agents
(b) mAB's as targeting agents
3. Protein Purification

45.How will you classify liposomes?

Classification of Liposomes
The Liposomes may be classified based on:
1. Structure.
2. Method of preparation.
3. Composition.
4. Conventional liposome.
5. Speciality liposome.

46.Give advantages of nanoparticles.

Advantages of Nanoparticles
1. They are suitable for different routes of administration.
2. Carrying capacity of nanoparticles is high.
3. Shelf-stability of drug increases.
4. Ability to sustain and control drug release patterns.
5. Suitable for combination therapy where two or more drugs can be co-delivered.
6. Both hydrophobic and hydrophilic drug can be incorporated. 7. System increases the bioavailability of drugs.
8. Imaging studies can be done by utilizing them.
9. It is used for targeted drug delivery of drugs.
10. Development of new medicines which are safer.

47.What is size range of colloidal particles?

A colloidal particle is a small particle with dimension scale ranging from nanometers to micrometers, depending on
the specific colloidal behavior under consideration.
Their range of diameters of colloidal particles is between 1 and 1000 nm, i.e. from 10-9 to 10-6 m.

48.What is major problem of nanoparticles?

1. The manufacturing costs of Nanoparticles are high, which result in increase in overall product cost.
2. Solvents are toxic in nature which are used in the preparation process.
3. Can start immune response and allergic reactions in body.
4. Extensive use of poly (vinyl alcohol) as stabilizer may have toxicity issues.
5. Nanoparticles are difficult to handle in physical form because particle-particle aggregation occurs due to their
small size and large surface area.

49.Write disadvantages of CDDS.

DISADVANTAGES OF CONTROLLED DRUG DELIVERY
1. Dumping is a major disadvantage of CRDDS, which refers to the rapid release of a relatively large quantity of
drug from a controlled release formulation. This phenomenon becomes hazardous with potent drugs.
2. Poor in-vivo and in-vitro correlations.
3. Difficult to optimize the accurate dose and dosing interval.
4. Patient variability affects the release rate like GI emptying rate, residential time, fasting or non-fasting condition,
etc.
50.Enlist the factors affecting design of CRDDS.
A. Physiological Properties
(1) Aqueous solubility:
(2) Partition coefficient (P-value):
(3) Drug pKa:
(4) Drug stability:
(5) Molecular size and molecular weight:
(6) Protein binding:
B. Biological Properties
(1) Absorption:
(2) Distribution:
(3) Elimination:
(4) Biological half-life (t1/2):
(5) Dose size:
(6) Therapeutic window:
(7) Absorption window:
(8) Patient physiology:

51.What is mean by microcapsule and microsphere?

Microcapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small
capsules, of many useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other
materials on a micro metric scale.
Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers having a
particle size ranging from 1-1000 μm. The range of Techniques for the preparation of microspheres offers a variety
of opportunities to control aspects of drug administration and enhance the therapeutic efficacy of a given drug.

52.Write inotropic gelation method for preparation of microencapsulation.

Ionotropic Gelation Technique : In the ionotropic gelation method, polysaccharides (alginate, gellan and pectin)
are dissolved in water or in weak acidic medium (chitosan). These solutions are then added drop wise under
constant stirring to the solutions containing other counter ions. Due to the complexation between oppositely
charged species, polysaccharides undergo ionic gelation and precipitate to form spherical particles. The beads are
removed by filtration, washed with distilled water and dried. The method involves an all-aqueous system and
avoids residual solvents in microspheres.

53.Define monoclonal antibodies and enlist methods of preparation.

MONOCLONAL ANTIBODIES : Monoclonal antibodies are identical immunoglobulins, generated from a
single B-Cell clone. These antibodies recognize unique epitopes or binding sites on a single antigen. Derivation
from a single B-Cell clones and subsequent targeting of a single epitome is what differentiates monoclonal
antibodies from polyclonal antibodies.
Polyclonal antibodies are antibodies that are derived from different cell lines. They differ in amino acid sequences.
Methods of Preparation : 1. By Injection into the peritoneal cavity of a suitably prepared mouse (in vivo method).
2. In vitro Tissue Culture.

54.Give the advantages of implantable drug delivery system.

Advantages of IDDS
1. Convenience:
2. Compliance
3. Improved drug delivery
4. Potential for controlled release
5. Potential for intermittent release
6. Flexibility

55.What is difference between nasal and pulmonary drug delivery systems?

56.Enlist the polymers used in the formulation of pharmaceuticals.
1. Poly (lactic acid)
2. Poly (lactic-co-glycolic acid)
3. Polyanhydrides
4. Poly (ortho esters)
5. Poly (phosphoesters).

57.Differentiate between dry powder inhaler and metered dose inhaler.

58.Give applications of nanoparticles.
Applications of Nanoparticles
1. Nanoparticles for transdermal for application for improved absorption and permeation.
2. Nanoparticles for enzyme immunoassays with adsorbed enzymes.
3. Nanoparticles for radioactive or contrast agents for Radio-Imaging.
4. Nanoparticles as functionalized nanoparticles for enzyme immobilization, controlled release polymeric systems,
etc.

59.Write note on ocuserts.

Ocuserts: It is a flat, flexible, elliptical device designed to be placed in the inferior cul- de-sac between the sclera
and eyelid which releases Pilocarpine continuously at a steady state for 7 days.
It comprises of 3 layers:
1. Outer Layer: Ethylene vinyl acetate copolymer layer.
2. Inner Layer: Pilocarpine gelled with alginate main polymer.
3. A retaining ring of EVA impregnated with titanium dioxide. Example: Pilo 20 (20 mg/hr), Pilo 40 (40 mg/hr).

60.Write mechanism of IUDs.

1. Intrauterine devices (IUDs) are small, T-shaped contraceptive devices inserted into the uterus.
2. IUDs primarily work by releasing either copper or hormones, which affect the uterine environment, making it
less favorable for fertilization and implantation of an egg.
3. Copper IUDs create an inhospitable environment for sperm, inhibiting their movement and viability.
4. Hormonal IUDs release progestin, which thickens cervical mucus, preventing sperm from reaching the egg, and
thins the uterine lining, reducing the chances of implantation.
5. IUDs do not affect ovulation in most cases but primarily act by altering the uterine environment to prevent
pregnancy.
6. IUDs are highly effective, long-lasting contraceptives that provide a reversible and convenient method of birth
control.

61.Give problems to design buccal drug delivery system.

1. Ensuring proper drug absorption: Designing a buccal drug delivery system requires overcoming challenges
related to drug absorption through the buccal mucosa, such as limited permeability and enzymatic degradation.
2. Maintaining drug stability: The design should address issues of drug stability, preventing degradation or loss
of potency during storage and administration in the buccal cavity.
3. Achieving controlled release: Developing a system that allows for controlled release of the drug, maintaining
therapeutic levels over a desired duration, presents a significant challenge in buccal drug delivery design.
4. Enhancing patient compliance: Designing a user-friendly and comfortable buccal drug delivery system is
essential to ensure patient acceptance and compliance, considering factors such as ease of administration, taste, and
potential side effects.

62.Give disadvantages of eye drops?

Stinging / redness in the eye,
Widened pupils.
Blurred vision.
Drug - resistant bacterial infection in eyes.
Irritation in eyes.
Burning sensation in eyes.
Watery eyes.

63.Which excipients are used to design floating drug delivery system?

Floating drug delivery systems are designed to float on the gastric fluid and release the drug in a controlled manner.
To achieve this, various excipients can be used in the formulation. Here are some commonly used excipients in the
design of floating drug delivery systems:
1. Polymers
2. Effervescent Agents
3. Fillers
4. Gelling Agents
5. Surfactants
6. Gas - Generating Agents
7. Coating Agents
8. pH Modifiers
64.Enlist different osmotic agents.
Osmotic agents are substances that can increase the osmolarity of a solution and create an osmotic pressure
gradient across a semipermeable membrane. They are used in various medical and pharmaceutical applications.
Here are some examples of osmotic agents:
1. Mannitol
2. Sodium chloride
3. Glycerin
4. Isosorbide
5. Urea
6. Sorbitol

65.Write advantages of natural polymers.

Advantages of Natural polymers
1. Inherently bioactive
2. Possess cell-interactive groups on their backbones
3. Offer better cell attachment, growth, multiplication and differentiation
4. Chemically benign degradation products
5. Elicit low immune response
6. Biocompatible
Long answer questions (5 marks)
1. Explain physicochemical properties of drugs relevant to controlled release formulations.
Physiological Properties
(1) Aqueous solubility: Most of the active pharmaceutical moiety (API) are weakly acidic or basic in nature that
affect the water solubility of API. Weak water-soluble drugs are difficult to design the controlled release
formulations. High aqueous solubility drug show burst release followed by a rapid increment in plasma drug
concentration. These types of drugs are a good candidate for CRDDS. The pH dependent solubility also creates a
problem in formulating CRDDS. BCS class-III and IV drugs are not a suitable candidate for this type of
formulations.
Determination of Solubility:
1. Semi-quantitative method. 2. Accurate-quantitative method. 3. pH change method.
Absorption of poorly soluble drugs is often dissolution rate-limited. Such drugs do not require any further
control over their dissolution rate and thus may not seem to be good candidates for oral controlled release
formulations. Controlled release formulations of such drugs may be aimed at making their dissolution more
uniform rather than reducing it.
(2) Partition coefficient (P-value): P-value denotes the fraction of the drug into oil and aqueous phase that is a
significant factor that affects the passive diffusion of the drug across the biological membrane. The drugs are
having high or low P value not suitable for CR, it should be appropriate to dissolve in both phases.
The partition coefficient is defined as "the concentration ratio of unionized drug distributed between two
phases at equilibrium".
• Given by the Noyes-Whitney's Equation:
P = ([𝐀][𝐀]∞)
• The logarithm (base 10) of the partition coefficient (log 10 P) is often used.
• For ionizable drugs, where the ionized species does not partition into the organic phase, the apparent partition
coefficient, (D), can be calculated as:
Acids: log 10 D = log 10 P - log 10 (1 + 10 (pH - pKa))
Bases: log 10 D = log 10 P - log 10 (1 + 10 (pKa - pH))
• The octanol-water partition coefficient, has been widely used as a measurement for determining the relative
lipophilicity of a drug. Drugs that are very lipid soluble or very water-soluble i.e., extremes in partition coefficient,
will demonstrate:
1. Either low flux into the tissues or
2. Rapid flux followed by accumulation in tissues.
• Both cases are undesirable for controlled release system.
(3) Drug pKa: pKa is the factor that determine the ionization of drug at physiological pH in GIT. Generally, the
high ionized drugs are poor candidates for CRDDS. The absorption of the unionized drug occurs rapidly as
compared to ionized drugs from the biological membranes. The pKa range for an acidic drug that ionization
depends on the pH is 3.0 to 7.5 and for a basic drug it lay between 7 and 11.
(4) Drug stability: Drugs that are stable in acid/base, enzymatic degradation, and other gastric fluids are good
candidates for CRDDS. If drug is degraded in the stomach and small intestine, it is not suitable for controlled
release formulations because it will decrease in bioavailability of concern drug.
(5) Molecular size and molecular weight: The molecular size and molecular weight are wo important factors
which affect the molecular diffusibility across a biological membrane. The molecular size less than 400D is easily
diffused but greater than 400D create a problem n drug diffusion.
(i) In addition to diffusion through a variety of biological membranes, drugs in many CRDDS must diffuse through
a rate controlling membrane or matrix.
(ii) The ability of drug to pass through membranes is called as diffusivity.
(iii) An important influence upon the value of diffusivity-D, in polymers is the molecular size of the diffusing
species.
(iv) The value of D thus, is related to the size and shape of the cavities as well as size and shape of the drugs.
(v) Molecular size of the drug plays a major role when it comes to diffusion of the drug through a biological
membrane.
(6) Protein binding: The drug-protein complex act as a reservoir in plasma for the drug. Drugs showing high
plasma protein binding are not a good candidate for CRDDS because the protein binding increases the biological
half-life. So, there is no need to sustain the drug release.
This complex leads to :
1. Inhibition of therapeutic effect of such amount. 2. Half-life is increased (compared to in vitro studies).
3. Toxicity profiles elevated.
Thus, in most of the cases, protein binding is undesirable. Many drugs are highly protein bound (may be 95%),
thus the need of formulating a modified drug or drug delivery system starts.
2. Describe diffusion controlled drug delivery systems.
3. Explain properties of polymers relevant to design of drug delivery systems.
Polymers : Polymers are compounds with high molecular masses formed by monomers. In Greek, the word poly
means 'many' and meros means 'units or parts'. Polymers play a major role in the development of drug delivery
technology by release of two types of drugs like; hydrophilic and hydrophobic in a synchronized manner and
constant release of formulations over extended periods. There are numerous advantages of polymers acting as an
inert carrier to which a drug can be conjugated, for example the polymer improves the pharmacokinetic and
pharmacodynamic properties of biopharmaceuticals through various ways like; plasma half-life, decreases the
immunogenicity, build ups the stability of biopharmaceuticals, improves the solubility of low molecular weight
drugs, and has a potential of targeted drug delivery. However, they have their own limitations, such as; the natural
polymers are most abundant and biodegradable but are difficult to reproduce and purify. Synthetic polymers have
high immunogenicity, which prevent their long term usage. Non-biodegradable polymers are needed to be sugary
after they release the drug at the targeted The general characteristic features that makes the polymer a potential
candidate for drug delivery include; safety, efficacy, hydrophilicity, absence immunogenicity biological inactivity,
sufficient pharmacokinetics and presence of functional groups for covalent conjugation of drugs, targeting moieties
or formation of copolymer.
Characteristics of Ideal Polymer
1. Low density.
2. Low coefficient of friction.
3. Good corrosion resistance.
4. Good mould ability.
5. Excellent surface finish can be obtained.
6. Can be produced with close dimensional tolerances.
7. Economical.
8. Poor tensile strength.
9. Low mechanical properties.
10. Poor temperature resistance.
11. Can be produced transparent or in different colours.
Advantages of Ideal Polymer
1. Polymers used in colloidal drug carrier systems, consisting of small particles, show great advantage in drug
delivery systems because of optimized drug loading and releasing property.
2. A polymer (natural or synthetic) is aggregated with a drug in controlled drug delivery and hence it gives an
effective and controlled dose of drug, avoiding overdose.
3. The degradable polymers are ruptured into biologically suitable molecules that are assimilated and discarded
from the body through normal route.
4. Reservoir based polymers is advantageous in various ways like it increase the solubility of incompetently soluble
drugs and it lowers the antagonistic side effects of drugs.
5. Magneto-optical polymer coated and targeted nanoparticles are multimodal (optically and MRI detectable) while
Quantum Dots are only optically detectable.
6. Some Quantum dots contain Ca which is known to be toxic to humans.. Magneto/optical nanoparticles whether
polymer coated or targeted are composed of iron oxides/polymers which are known to be safe, therefore have great
future.
7. Dextran is the common polymer used for coating of iron oxide (plasma expander and affinity for iron) and are
used for treatment of iron anaemias since 1960 and is still in operation.
8. In controlled release, some of the polymers like; polyurethanes for elasticity, polysiloxanes for insulating ability
are used for their intended non-biological physical properties.
9. Current polymers like; Poly 2-hydroxy ethyl methacrylate, Polyvinyl alcohol, Polyethylene glycol are used
because of their inert characteristics and also, they are free of leachable impurities.
10. In biodegradable polymers, the system is biocompatible and it will not show dose leaving behind at any time,
and the polymer will keep its properties until after exhaustion of the drug.
Polymer Classification
The polymers are classified in to various types based on different categories. They are:
Classification of polymer
A. Based on origin of Source
1. Natural polymers
2. Semi-synthetic polymer
3. Synthetic polymers
B. Based on structure
1. Linear polymers
2. Branched chain polymers
3. Cross-linked
C. Based on molecular forces
1. Elastomers
2. Fibers
3. Thermoplastics
4. Thermosetting polymers
D. Based on mode of polymerization
1. Addition polymers
2. Condensation polymers

4. Write application of polymers in formulation of controlled release drug delivery systems.

Applications of Polymers in Formulation of Controlled Drug Delivery System
1. Osmotic Pressure-Controlled GI Delivery System
Semi-permeable membrane is made from biocompatible polymers. E.g. cellulose acetate
Example of such type of system include, Acutrim tablet which contains Phenylpropanolamine as a drug.
2. Gel Diffusion Controlled GI Delivery System Diffusion and Dissolution-Controlled Release System :
1. Drug is encased in a partially soluble membrane.
2. Pores are created due to dissolution parts of membrane.
3. It permits entry of aqueous medium into core and drug dissolution.
4. Diffusion of dissolved out of system.
Example: Ethyl cellulose and PVP mixture dissolves in water and create pores of insoluble ethyl cellulose
membrane.
3. Mucoadhesive GI Delivery System: The new generation mucoadhesive polymers for buccal drug delivery with
advantages such as; increase in the residence time of the polymer, penetration enhancement, site specific adhesion
and enzymatic inhibition, site specific mucoadhesive polymers will undoubtedly be utilized for the buccal delivery
of a wide variety of therapeutic compounds. The class of polymers has enormous potential for the delivery of
therapeutic macromolecules.
4. Transdermal Drug Delivery System: TDDS is defined as, self-contained, self-discrete dosage forms, which
when applied to the intact skin, delivers the drug at a controlled rate to the systemic circulation. In this, polymer
matrix plays a major role. It releases the drug from the device to the skin.
Advantages of Transdermal Drug Delivery System:
a) They permit easy removal and termination of drug action in situation of toxicity.
b) Problems encountered with oral administration like; degradation, gastric irritation, etc. are avoided.
5. Ocular Drug Delivery System: It allows prolonged contact of drug with corneal surface of eye. The example
for ODDS is pilocarpine in the treatment of glaucoma. In this, muco-adhesive polymers are used as barriers to
control the drug release. For e.g. Polyacrylic acid, Co polymers of acetate vinyl and ethyl.
6. Other Applications
1. Drug Delivery and the Treatment of Diabetes: Here the polymer will act as a barrier between blood stream
and insulin.
E.g. Polyacrylamide or N,N-Dimethyl amino ethylmetha acrylate.
2. Drug Delivery of Various Contraceptives and Hormones: It consists of drug saturated liquid medium
encapsulated in polymeric layer which controls the concentration and release of drugs into the blood stream.
Eg. Medoxy progesterone acetate, Progestasert, Duromine, etc.
5. Enlist method of mincroencapsulation and discuss any two methods.
Microencapsulation Technique
A. Physical or physico-mechanical
1. Air suspension
2. Centrifugal extrusion
3. Pan coating
4. Spray-drying
4.1 Co-current
4.2 Counter-current
4.3 Mixed-flow
5. Vibrational nozzle
B. Physico-chemical
1. Ionotropic gelation
2. Coacervation
C. Chemical
1. Solvent Evaporation
2. Polymerization
2.1 Interfacial polymer
2.2 In-situ polymerization
2.3 Matrix polymer
1. Air suspension
The Wruster Process
1. This technology is characterized by the location of a spray nozzle at the bottom of a fluidized bed of solid
particles.
2. The particles are suspended in the fluidizing air stream that is designed to induce a cyclic flow of the particles
past the spray nozzle.
3. The nozzle sprays an atomized flow of coating solution, suspension, or other coating vehicle.
4. The technology can be used to encapsulate solid materials with diameters ranging from near 50 μm to several
centimeters.
5. Wruster Process can be used to encapsulate vitamins, minerals, and functional food ingredients.
6. It consists of dispersing the solid particulate core material in supporting air stream and being coated with coating
material (usually polymeric solution).
7. In this, the fine core materials are suspended in a vertical current of air and sprayed with the coating material.
8. After evaporation of solvent, a layer of encapsulating material is deposited on core.
9. Gives improved control and flexibility as compared to pan coating.
10. During each pass through the coating zone, the core material receives an increment of coating material.
11. The cyclic process is repeated, perhaps several hundred times during processing, depending on the purpose of
microencapsulation the coating thickness desired or whether the core material particles are thoroughly
encapsulated.
12. The supporting air stream also serves to dry the product while it is being encapsulated.
13. Drying rates are directly related to the volume temperature of the supporting air stream.
Disadvantage: Agglomeration of the particles to some larger size is normally achieved.
2. Pan Coating
1. Oldest industrial procedures for forming small, coated particles or tablets.
2. The particles are tumbled in a pan or other device while the coating material is applied slowly.
3. Solid particles greater than 600 microns in size are generally considered essential for effective coating.
4. Medicaments are usually coated onto various spherical substrates such as; nonparell sugar seeds, and then coated
with protective layers of various polymers.
5. It is used for preparation of controlled-release beads.
6. Coating is applied as solution by automized spray to desired solid core material in coating pan.
7. Usually warm air is passed over the coated material as the coating are being applied in the coating pan.
8. Solid particles are mixed with a dry coating material.
9. The temperature is raised so that the coating material melts and encloses the core particles, and then is solidified
by cooling.

6. What is mean by mucoadhesion? Enlist theories of mucoadhesion and explain any one.
MUCOADHESION / BIOADHESION : Mucoadhesive drug delivery system are the systems which utilizes the
property of bio adhesion of certain polymers which become adhesive on hydration and can be used for targeting a
drug to a particular region of the body for extended periods of time.
The term "mucoadhesion" was coined for the adhesion of the polymers with the surface of the mucosal layer. Bio
adhesions are a phenomenon in which two materials at least one of which is biological and are held together by
means of interfacial forces.
The phenomena of bioadhesion occur by a complex mechanism. Six theories have been proposed, which will
explain the mechanism of bioadhesion. The theories are as follows:
(a) Electronic theory: Involves the formation of an electric double layer at the mucoadhesive interface by the
transfer of electrons between the mucoadhesive polymer and the mucin glycoprotein network. For example:
Interaction between positively charged polymers chitosan and negatively charged mucosal surface which becomes
adhesive on hydration and provides an intimate contact between a dosage form and absorbing tissue.
(b) Wetting Theory: States that if the contact angle of liquids on the substrate surface is lower, then there is a
greater affinity for the liquid to the substrate surface. If two such substrate surfaces are brought in contact with each
other in the presence of the liquid, the liquid may act as an adhesive amongst the substrate surfaces.
(c) Adsorption Theory: According to this theory, after an initial contact between two surfaces, the material
adheres because of surface force acting between the atoms in two surfaces. Two types of chemical bonds resulting
from these forces can be distinguished as primary chemical bonds of covalent nature and Secondary chemical
bonds having many different forces of attraction likes electrostatic forces, Vander Walls forces, hydrogen and
hydrophobic bonds.
(d) Diffusion Theory: According to this theory, the polymer chains and the mucus mix to a sufficient depth to
create a semi-permanent adhesive bond. The exact depth to which the polymer chain penetrates the mucus depends
on the diffusion coefficient and the time of contact. The diffusion coefficient in terms depends on the value of
molecular weight between cross linking and decreases significantly as the cross linking density increases.
(e) Mechanical Theory: Explains the diffusion of the liquid adhesives into the micro- cracks and irregularities
present on the substrate surface thereby forming an interlocked structure which gives rise to adhesion.
(f) Cohesive Theory: Proposes that the phenomena of bio adhesion are mainly due to the intermolecular
interactions amongst like-molecules. Based on the above theories, the process of bio adhesion can be broadly
classified into two categories.
• Chemical: Electronic and adsorption theories.
• Physical: Wetting, diffusion and cohesive theory.
The process of adhesion may be divided into two stages. During the first stage (also Known as contact stage),
wetting of mucoadhesive polymer and mucous membrane occurs followed by the consolidation stage, where the
physicochemical interactions take place.

7. Give formulation considerations of buccal drug delivery systems.

BUCCAL DELIVERY SYSTEM : Buccal drug delivery systems interact with the mucus layer covering the
mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of
absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract
(GIT) require increased duration of stay in GIT. Thus, buccal dosage forms are advantageous in increasing the drug
plasma concentrations and also therapeutic activity.
Formulation Design : Pharmaceutical considerations: Great care needs to be exercised while developing a safe
and effective buccal adhesive drug delivery device. Factors influencing drug release and penetration through buccal
mucosa are organoleptic factors and effects of additives used to improve drug release pattern and absorption, the
effects of local drug irritation caused at the site of application are to be considered while designing a formulation.
1. Physiological Considerations : Physiological considerations such as; texture of buccal mucosa, thickness of the
mucus layer, its turn over time, effect of saliva and other environmental factors are to be considered in designing
the dosage forms.
For e.g. Saliva contains moderate levels of esterases, carbohydrases, and phosphatases that may degrade certain
drugs. Although saliva secretion facilitates the dissolution of drug, involuntary swallowing of saliva also affects its
bioavailability
2. Pharmacological Considerations : Drug absorption depends on the partition coefficient of the drugs. Generally,
lipophilic drugs absorb through the transcellular route, whereas; hydrophilic drugs absorb through the paracellular
route. Chemical modification may increase drug penetration through buccal mucosa. Residence time and local
concentration of the drug in the mucosa, the amount of drug transported across the mucosa into the blood are the
responsible factors for local or systemic drug delivery. Optimization by a suitable formulation design fastens drug
release from the dosage form taken up by the oral mucosa.
8. Write a note on osmotic pumps.

9. Enlist formulation approaches for transdermal drug delivery systems and explain any one approach.
10.Describe the components of transdermal DDS.
BASIC COMPONENTS OF TDDS
1. Polymer matrix/drug reservoir voirg.
2. Membrane
3. Drug
4. Permeation enhancers
5. Pressure-sensitive adhesives (PSA)
6. Backing laminates
7. Release liner
8. Other excipients like plasticizers and solvents
1. Polymer Matrix/Drug Reservoir : Polymers are the backbone of TDDS, which control the release of the drug
from the device. A polymer matrix can be prepared by dispersion of drug in a liquid or solid state synthetic
polymer base. Polymers used in TDDS should have biocompatibility and chemical compatibility with the drug and
other components of the system, such as penetration enhancers and PSAs.
2. Membrane : A membrane may be sealed to the backing to form a pocket to enclose the drug- containing matrix
or used as a single layer in the patch construction. The diffusion properties of the membrane are used to control
availability of the drug and/or excipients to the skin. For example, ethylene vinyl acetate, silicone rubber,
polyurethane, etc. are used as a rate- controlling membrane.
3. Drug : For successfully developing a TDDS, the drug should be chosen with great care. Transdermal patches
offer many advantages to drugs that undergo extensive first-pass metabolism, drugs with narrow therapeutic
window or drugs with a short half-life, which cause non-compliance due to frequent dosing.
4. Permeation Enhancers : One long-standing approach for improving TDD uses penetration enhancers (also
called sorption promoters or accelerants), which increase the permeability of the SC so as to attain higher
therapeutic levels of the drug candidate.
5. PSAs : Widely used PSA polymers in TDDS are polyisobutylene-based adhesives, acrylics and silicone-based
PSAs, hydrocarbon resin, etc. The PSA can be located around the edge of the TDDS or be laminated as a
continuous adhesive layer on the TDDS surface. The PSA should be compatible with the drug and excipients, as
their presence can modify the mechanical characteristics of the PSA and the drug delivery rate.
6. Backing Laminates : Backings are chosen for appearance, flexibility and need for occlusion; hence, while
designing a backing layer, the consideration of chemical resistance of the material is most important. Excipient
compatibility should also be considered because the prolonged contact between the backing layer and the
excipients may cause the additives to leach out of the backing layer or may lead to diffusion of excipients, drug or
penetration enhancer through the layer.
7. Release Liner : During storage, the patch is covered by a protective liner that is removed and discarded before
the application of the patch to the skin. Because the liner is in intimate contact with the TDDS, the liner should be
chemically inert. Typically, a release liner is composed of a base layer that may be non-occlusive (e.g. paper fabric)
or occlusive (e.g. polyethylene, polyvinyl chloride) and a release coating layer made up of silicon or teflon. Other
materials used for TDDS release liner are polyester foil and metalized laminates.
8. Other Excipients Like Plasticizers and Solvents : Various solvents such as; chloroform, methanol, acetone,
isopropanol and dichloromethane are used to prepare drug reservoir. In addition, plasticizers such as; dibutyl
phthalate, triethyl citrate, polyethylene glycol and propylene glycol are added to provide plasticity to the
transdermal patch.

11.Enlist various factors affecting to transdermal permeation of drug and explain any two.
FACTORS AFFECTING TRANSDERMAL DRUG DELIVERY SYSTEM
A. Physicochemical Properties of Drug
Following are the Physiochemical Properties of the Drug:
1. Partition coefficient
2. Molecular size
3. Solubility/Melting point
4. Ionization
5. Diffusion Coefficient
1. Partition Coefficient : Drug possess both water and lipid solubility. Ideal partition coefficient for intermediate
transdermal delivery is log K1-3. For highly lipophilic drug (log k < 3), intracellular route is favourable, whereas for
hydrophilic drugs (log k < 1), it is permeated via transcellular route.
2. Molecular Size : Molecular size of the drug is inversely proportional to transdermal flux. The ideal molecular
size of drug molecule for transdermal delivery is ≤400.
3. Solubility/Melting Point : Most organic solutes have high melting point and low solubility at normal
temperature and pressure. Lipophilic drug permeates faster than hydrophilic substances, but it should also have
aqueous solubility as needed in most of topical formulations.
4. Ionization : Unionized drug permeates the skin as according to pH-Partition hypothesis.
5. Diffusion Coefficient : Penetration of drug depends on diffusion coefficient of drug. At a constant temperature,
the diffusion coefficient of drug mainly depends on properties of drug, diffusion medium and their interaction.
B. Physicochemical Properties of Drug Delivery System
Following are the Physicochemical Properties of Drug Delivery System:
1. Release characteristics.
2. Composition of drug delivery system.
3. Enhancement of Transdermal permeation.
1. Release Characteristics : Drug release mechanism mainly depends on drug molecules which are dissolved or
suspended in the delivery system and on interfacial partition coefficient or pH of the drug from delivery system to
the skin tissue. If the drug is easily released from the delivery system, the rate of transdermal permeation will be
higher.
2. Composition of Drug Delivery System : Composition may not affect release properties but may affect its
permeability functionality. For example, methyl salicylate is more lipophilic than parent acid, i.e. salicylic acid, and
its percutaneous absorption is high when applied to skin in a lipoidal vehicle.
3. Enhancement of Transdermal Permeation : Majority of drugs will not permeate into skin for therapeutic use.
Some enhancers are used for synergistic action without showing its properties (e.g. dimethyl sulphoxide, acetone,
propylene glycol and tetradihydrofuryl alcohol).
C. Physiological Properties
Following are the Physiological and Pathological Conditions of Skin:
1. Skin permeation barrier in neonate and infants 2. Skin barrier properties in aged skin
3. Race 4. Skin temperature

12.What is mean by gastroretentive drug delivery system? Explain any one approach to design gastroretentive
drug delivery system.
GASTRO-RETENTIVE DRUG DELIVERY SYSTEMS
Gastro-Retentive Drug Delivery System (GRDDS) has gained immense popularity in the field of oral drug
delivery recently. It is a widely employed approach to retain the dosage form in the stomach for an extended period
of time and release the drug slowly that can address many challenges associated with conventional oral delivery,
including poor bioavailability. Different innovative approaches like magnetic field assisted gastro-retention, plug
type swelling system, muco-adhesion technique, floating system with or without effervescence are being applied to
fabricate GRDDS.
Approaches for GRDDS
1. Floating drug delivery systems.
2. Mucoadhesive systems.
3. Swellable systems.
4. High density systems.
Bioadhesive or Mucoadhesive Drug Delivery Systems : Bioadhesive drug delivery systems are used as a delivery
device within the human to enhance drug absorption in a site-specific manner. In this approach, bio-adhesive
polymers are used and they can adhere to the epithelial surface in the stomach.
Thus, they improve the prolongation of gastric retention. The basis of adhesion is that, a dosage form can stick
to the mucosal surface by different mechanisms. These mechanisms are:
1. The wetting theory, which is based on the ability of bioadhesive polymers to spread and develop intimate contact
with the mucous layers.
2. The diffusion theory, which proposes physical entanglement of mucin strands the flexible polymer chains, or an
interpenetration of mucin strands into the porous structure of the polymer substrate.
3. The absorption theory, suggests that bio-adhesion is due to secondary forces such as; vander Waal forces and
hydrogen bonding.
4. The electron theory, which proposes attractive electrostatic forces between the glycoprotein mucin network and
the bio-adhesive material.
Materials commonly used for bioadhesion are poly acrylic acid, chitosan, cholestyramine, sodium alginate,
hydroxypropyl methylcellulose (HPMC), sucralfate, tragacanth, dextrin, polyethylene glycol (PEG) and polylactic
acids, etc. Even though some of these polymers are effective at producing bioadhesive, it is very difficult to
maintain it effectively because of the rapid turnover of mucus in the gastrointestinal tract (GIT).
Advantages of GRDDS
1. Enhanced bio-availability. 2. Reduced frequency of dosing.
3. Targeted therapy for local ailments in the upper GIT. 4. Patient compliance.
5. Improved therapeutic efficacy.
13.Write formulation of dry powder and metered dose inhalers.
 FORMULATION OF DRY POWDER INHALERS (DPI)
• DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix (DPI) that is fluidized when the
patient inhales.
• DPIs are typically formulated as one-phase, solid particles blends. The drug with particle sizes of less than 5 μm
is used
• DPIs are a widely accepted inhaled delivery dosage form, particularly in Europe, where they are currently used by
approximately 40% of asthma patients.
Advantages :
1. Propellant free.
2. Less need for patient co-ordination.
3. Less formulation problems.
4. Dry powders are at a lower energy state, which reduces the rate of chemical degradation.
Disadvantages:
1. Dependency on patient's inspiratory flow rate and profile.
2. Device resistance and other design issues.
3. Greater potential problems in dose uniformity.
4. More expensive than pressurized metered dose inhalers.
 FORMULATION OF METERED DOSE INHALERS (MDI)
• These are used in treatment of respiratory diseases such as, asthma and COPD.
• They can be given in the form of suspension or solution.
• The particle size of less than 5 microns is observed here.
• This is used to minimize the number of administration errors. The main advantage is that, it can deliver measured
amount of medicament accurately.
Advantages:
1. It delivers specified amount of drug.
2. Small size and convenience.
3. Usually inexpensive as compared to dry powder inhalers and nebulizers.
4. Quick to use.
5. Multidose capability more than 100 doses available.
Disadvantages-
1. Difficult to deliver high doses.
2. The remaining amount of doses is not known in MDI.
3. Accurate co-ordination between activation of a dose and inhalation is essential.

14.Write a note on nebulizers.

15.Explain concept, advantages and disadvantages of liposomes.
LIPOSOMES
Liposomes are concentric bi-layered vesicles in which an aqueous volume is entirely -nclosed by a membranous
lipid bilayer mainly composed of natural or synthetic phospholipids.
Liposomes are microscopic spheres made from fatty materials, predominantly phospholipids.
Liposomes are made up of one or more concentric lipid bilayers, and range in size from 50 nanometers to several
micrometers in diameter.
Structural Components of Liposomes
The main components of liposomes are:
1. Phospholipids
2. Cholesterol
Classification of Liposomes
The Liposomes may be classified based on:
1. Structure.
2. Method of preparation.
3. Composition.
4. Conventional liposome.
5. Speciality liposome.
Advantages of Liposomes
1. Provides selective passive targeting to tumor tissues (liposomal doxorubicin).
2. Increases efficacy and therapeutic index.
3. Increased stability via encapsulation.
4. Reduced toxicity of the encapsulated agent.
5. Site avoidance effect.
6. Improved pharmacokinetic effect (reduced elimination, increased circulating life time).
7. Flexibility to couple with site specific ligands to achieve active targeting.
Disadvantages of Liposomes
1. Production cost is high.
2. Leakage and fusion of encapsulated drug/molecules.
3. Sometimes phospholipids undergo oxidation and hydrolysis like reaction.
4. Short half life.
5. Low solubility.

16.What are niosomes? Write its applications in targeted drug delivery system.
NIOSOMES : Niosomes are a novel drug delivery system, which entrapped the hydrophilic drug in the core cavity
and hydrophobic drugs in the non-polar region present within the bilayer hence both hydrophilic and hydrophobic
drugs can be incorporated into niosomes. Niosomes are amphiphilic in nature, in which the medication is
encapsulated in a vesicle which is made by non-ionic surfactant vesicles and hence the name niosomes. Their size
is very small and microscopic. In the presence of proper mixtures of surfactants and charge inducing agents from
the thermodynamically stable vesicles. Niosomes are mostly studied as an alternative to liposomes because they
alleviate the disadvantages associated with liposomes.
Salient Features of Niosomes:
1. Niosomes can entrap solutes.
2. Niosomes are osmotically active and stable.
3. Niosomes can improve the performance of the drug molecules.
4. Better bioavailability at the particular site, just by protecting the drug from biological environment.
5. Niosomes increase the stability of the entrapped drug.
6. Niosomes prolong the circulation of the entrapped drug.
Applications of Niosomes
1. Better patient compliance and therapeutic effect than conventional formulations.
2. Show controlled and sustained release of drugs due to depot formation.
3. Effectively used in targeting of drugs.
4. More stable than liposome.
5. Administration through various routes like; oral, parenteral and topical, etc.
6. Biodegradable, Biocompatible and non-immunogenic to the body.
7. Handling, Storage and transportation is easy.
8. It can protect drug from enzymatic and acid thereby increasing stability of the drug.
9. It can be used in ocular drug delivery with no tissue irritation and damage by penetration enhancers.
10. To improve efficacy of drugs in cancer therapy.
11. In diagnostic imaging with carrier radio pharmaceutics.

17.Explain concept, advantages and disadvantages of nanoparticles.

NANOPARTICLES : Nano derives from the Greek word "Nanos" which means dwarf or extremely small. It can
be used as a prefix for any unit to mean a billionth of that unit. A Nanometer is a billionth of a meter or 10 -9 m.
• Nanoparticles are solid colloidal particles ranging from 1 to 1000 nm in size, they consist of macromolecular
materials in which the active ingredients (drug or biologically active material) is dissolved, entrapped or
encapsulated or adsorbed.
• Nano capsules are the ones in which the drug is confined to an aqueous or oily core surrounded by a shell-like
wall. Alternatively, the drug can be covalently attached to the surface or into the matrix.
Advantages of Nanoparticles
1. They are suitable for different routes of administration. 2. Carrying capacity of nanoparticles is high.
3. Shelf-stability of drug increases. 4. Ability to sustain and control drug release patterns.
5. Suitable for combination therapy where two or more drugs can be co-delivered.
6. Both hydrophobic and hydrophilic drug can be incorporated.
7. System increases the bioavailability of drugs.
8. Imaging studies can be done by utilizing them.
9. It is used for targeted drug delivery of drugs.
10. Development of new medicines which are safer.
Disadvantages of Nanoparticles
1. The manufacturing costs of Nanoparticles are high, which result in increase in overall product cost.
2. Solvents are toxic in nature which are used in the preparation process.
3. Can start immune response and allergic reactions in body.
4. Extensive use of poly (vinyl alcohol) as stabilizer may have toxicity issues.
5. Nanoparticles are difficult to handle in physical form because particle-particle aggregation occurs due to their
small size and large surface area.
18.Enlist various methods to overcome ocular barrier and describe any two methods.
Barriers To Ocular Drug Delivery : The reason why it is difficult to achieve relevant therapeutic doses within the
eye is primarily due to the presence of multiple barriers. When a dosage form is either administered topically or
systemically, it faces multiple obstacles before it reaches its site of action. As a result, ocular bioavailability from
topically administered drug is usually only 1%-7% of the applied dose. These barriers can be broadly classified as
anatomical barriers and physiological barriers.
1. Anatomical Barriers : When a dosage form is topically administered, there two routes of entry: either through
the cornea or via the non-corneal route.
(a) The cornea is a very tight multilayered tissue that is mainly composed of five sections:
(i) Epithelium-Principle barrier (Hydrophilic drug transport through intercellular spaces).
(ii) Bowman's membrane.
(iii) Stroma-multiple layers of collagen fibers containing pores and channels (for lipophilic drug, significant
barrier).
(iv) Descemet's membrane.
(v) Endothelium.
Prevention: Optimum bioavailability, right balance of lipophilic and hydrophilicity.
(b) Non-corneal route bypass the cornea and involves movement across conjunctiva and sclera.
(c) Conjunctiva: It is more permeable than cornea for hydrophilic molecules.
2. Physiological Barrier : The eye's primary line of defense is its tear film. Bioavailability of RAICE drugs is
further reduced by precorneal factors such as; solution drainage, tear dilution, tear turnover, and increased
lacrimation. This in turn lowers the exact time for absorption leading to reduced bioavailability.
Prevention: So, the drugs administered as eye drops need to be isotonic and non- irritating to prevent significant
precorneal loss.
3. Blood Ocular Barrier : This barrier normally keeps most drugs out of the eye, but inflammation breaks down
this barrier allowing drugs and large molecules to penetrate into the eye.
(a) Blood aqueous barrier: The ciliary epithelium and capillaries of the iris.
(b) Blood retinal barrier: Non-fenestrated capillaries of the retinal circulation and tight junctions between retinal
epithelial cells preventing passage of large molecules from chorio-capillaris into retina.
4. Drug and Dosage Form Related Factors:
(a) Solubility: Solubility is dependent on the pK, of the drug and pH of the solution.
(b) Lipophilicity: Lipophilicity and corneal permeability display sigmoidal relationship. This is because of the
differential permeability of the different layers of cornea towards lipophilic drugs. Lipophilic drugs tend to
permeate easily through the epithelial layers of cornea and the hydrophilicity of the inner layer of comea (stroma)
requires hydrophilicity for optimal permeation.
(c) Molecular weight and size: The weight and size of molecules play a critical role in deciding its overall
permeability through paracellular route. Molecules having molecular weight less than 500 Dalton are able to
permeate readily.
(i) The conjunctiva has larger paracellular pore diameter thus allowing permeation of larger molecules such as
small and medium size peptides (5000-10000 Daltons).
(ii) Permeation across sclera occurs through the aqueous pores and molecular size of the solute can be the
determining factor. Sucrose (molecular weight - 342 Daltons) permeates 16 times faster than inulin (molecular
weight - 5000 Daltons). Scleral permeability is approximately half of conjunctiva but much higher than cornea.
Advantages of Ocular Drug Delivery System
1. It can be easily administered.
2. They have quick absorption and effect.
3. Less visual and systemic side effects.
4. Better patient compliance.
Disadvantages of Ocular Drug Delivery System :
1. Residence time of drug at eye surface is less.
2. Poor bioavailability.
3. The instability of the dissolved drug.
4. The low concentration of preservative reduces shelf life after opening the bottle.
Ideal Characteristics of Ocular Drug Delivery System :
1. It should be sterile.
2. It should be isotonic to body fluids.
3. Buffer/pH adjustment.
4. Less drainage tendency.
5. Minimum protein binding.
19.What is mean by microencapsulation? Write reason for microencapsulation in pharmaceuticals.
• Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small
capsules, of many useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other
materials on a micro metric scale.
• Microencapsulation may be defined as, "the process of surrounding or enveloping one substance within another
substance on a very small scale, yielding capsules ranging from less than one micron to several hundred microns in
size". It is mean of applying thin coating to small particle of solid or droplet of liquid and dispersion.
• Microencapsulation is a process by which solids, liquids or even gases may be enclosed in microscopic particles
by formation of thin coatings of wall material around the substances.
REASONS FOR MICROENCAPSULATION
1. To protect reactive substances from the environment.
2. To convert liquid active components into a dry solid system.
3. To separate incompatible components for functional reasons
4. To protect the immediate environment of the microcapsules from the active components.
5. Isolation of core from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen.
6. Retarding evaporation of a volatile core.
7. Improving the handling properties of a sticky material.
8. Isolating a reactive core from chemical attack.
9. For safe handling of the toxic materials.
10. To get targeted release of the drug.
11. To control release of the active components for delayed (timed) release or long - acting (sustained) release.
12. The problem may be as simple as masking the taste or odor of the core.
13. To Increase of bioavailability.
14. To produce a targeted drug delivery.
15. Protects the GIT from irritant effects of the drug.
16. Extension of duration of activity for an equal level of active agent.
DISADVANTAGES OF MICROENCAPSULATION
1. It is an expensive process.
2. Requires skill.
3. Difficult to obtain continuous and uniform film.

20.Explain simple and complex coacervation phase separation method.

21.Write formulation of microencapsulation.
FORMULATION OF MICROENCAPSULATION
Generally Micro particles consist of two components:
(a) Core material: The solid core can be mixture of active constituents, stabilizers, diluents, excipients and
release-rate retardants or accelerators.
(b) Coat or wall or shell material: Compatible, non-reactive with core material. Provide desired coating
properties like; strength, flexibility, impermeability, optical properties, non-hygroscopicity, tasteless and stable.
Classification of Microencapsulation -
1. Core Material -
a) solid
b) liquid
2. Coating material -
a) Polymers
b) Waxes
c) Resins
d) Proteins
e) Polysaccharides
3. Vehicle
a) Aqueous
b) Non-aqueous
• Core Material - The material to be coated. It may be liquid or solid or gas. Liquid core may be dissolved or
dispersed material.
Composition of Core Material:
1. Drug or active constituent.
2. Additive like diluents.
3. Stabilizers
• Coating Material - Inert substance which coats on core with desired thickness.
Composition of Coating:
1. Inert polymer.
2. Plasticizer
3. Colouring agent.
4. Resins, waxes and lipids.
5. Release rate enhancers or retardants.
(a) Role of Polymers:
• Polymers are substances of high molecular weight made up by repeating monomer units. Polymer molecules may
be linear or branched, and separate linear or branched chains may be joined by crosslinks.
• Polymers are used widely in pharmaceutical systems as: adjuvants, coating materials and, a component of
controlled and site-specific drug delivery systems.
(b) Coating Material Properties:
1. Stabilization of core material.
2. Inert toward active ingredients.
3. Controlled release under specific conditions.
4. Film-forming, pliable, tasteless, stable.
5. Non-hygroscopic, no high viscosity, economical.
6. Soluble in an aqueous media or solvent, or melting.
7. The coating can be flexible, brittle, hard, thin, etc.

22.Explain chemical methods of microencapsulation.

23.Explain air suspension and extrusion method of microencapsulation.
Suspension and extrusion method of microencapsulation -
Inventions of Professor Dale E. Wurster :
• Basically, the wurster process consists of the dispersing of solid, particulate core materials in a supporting air
stream and the spray-coating of the air suspended particles. Equipment ranging in capacities from one pound to 990
pounds.
• Micron or submicron particles can be effectively encapsulated by air suspension techniques. Within the coating
chamber, particles are suspended on an upward moving air stream.
• The design of the chamber and its operating parameters effect a recalculating flow of the particles through the
coating zone portion of the chamber, where a coating material, usually a polymer solution, is spray applied to the
moving particles.
• The Wruster Process
1. This technology is characterized by the location of a spray nozzle at the bottom of a
fluidized bed of solid particles.
2. The particles are suspended in the fluidizing air stream that is designed to induce a
cyclic flow of the particles past the spray nozzle.
3. The nozzle sprays an atomized flow of coating solution, suspension, or other coating vehicle.
4. The technology can be used to encapsulate solid materials with diameters ranging from near 50 μm to several
centimeters.
5. Wruster Process can be used to encapsulate vitamins, minerals, and functional food ingredients.
6. It consists of dispersing the solid particulate core material in supporting air stream and being coated with coating
material (usually polymeric solution).
7. In this, the fine core materials are suspended in a vertical current of air and sprayed with the coating material.
8. After evaporation of solvent, a layer of encapsulating material is deposited on core.
9.Gives improved control and flexibility as compared to pan coating.
10. During each pass through the coating zone, the core material receives an increment of coating material.
11. The cyclic process is repeated, perhaps several hundred times during processing, depending on the purpose of
microencapsulation the coating thickness desired or whether the core material particles are thoroughly
encapsulated.
12. The supporting air stream also serves to dry the product while it is being encapsulated.
13. Drying rates are directly related to the volume temperature of the supporting air stream.
Disadvantage: Agglomeration of the particles to some larger size is normally achieved.
Variables for Efficient, Effective Encapsulation by Air Suspension Techniques:
1. Density, surface area, melting point, solubility, friability, volatility, crystallinity and flow-ability of core the core
material.
2. Coating material concentration (or melting point if not a solution).
3. Coating material application rate.
4. Volume of air required to support and fluidizes the core material.
5. Amount of coating material required.
6. Inlet and outlet operating temperatures.
24.Explain theories of mucoadhesion and mechanism of mucoadhesion.
Theories of Mucoadhesion -
The concept of mucoadhesion is one that has the potential to improve the highly variable residence times
experienced by drugs and dosage forms at various sites in the gastrointestinal tract, and consequently, to reduce
variability and improve efficacy.
Intimate contact with the mucosa should enhance absorption.
The mechanisms responsible in the formation of bio adhesive bonds are not fully known.
However, most research has described bioadhesive bond formation as a three-step process:
Step 1: Wetting and swelling of polymer.
Step 2: Interpenetration between the polymer chains and the mucosal membrane.
Step 3: Formation of Chemical bonds between the entangled chains.
1. Step 1: The wetting and swelling step occurs when the polymer spreads over the surface of the biological
substrate or mucosal membrane in order to develop an intimate contact with the substrate. This can be readily
achieved. For example, by placing a bioadhesive formulation such as; a tablet or paste within the oral cavity or
vagina. Bioadhesives are able to adhere to or bond with biological tissues by the help of the surface tension and
forces that exist at the site of adsorption or contact. Swelling of polymers occur because the components within the
polymers have an affinity for water.
2. Step 2 : The surface of mucosal membranes is composed of high molecular weight polymers known as
glycoproteins. In this step, interdiffusion and interpenetration take place between the chains of mucoadhesive
polymers and the mucous gel network creating a great area of contact. The strength of these bond depends on the
degree of penetration between the two polymer groups. In order to form strong adhesive bonds, one polymer group
must be soluble in the other and both polymer types must be of similar chemical structure.
3. Step 3: In this step, entanglement and formation of weak chemical bonds as well as secondary bonds between
the polymer chains mucin molecule. The types of bonding formed between the chains include primary bonds such
as covalent bonds and weaker secondary interactions such as van der Waals Interactions and hydrogen bonds. Both
primary and secondary bonds are exploited in the manufacture of bioadhesive formulations in which strong
adhesions between polymers are formed.

25.Write formulation design for mucoadhesive formulation with examples.

MUCOADHESION / BIOADHESION
Mucoadhesive drug delivery system are the systems which utilizes the property of bio adhesion of certain polymers
which become adhesive on hydration and can be used for targeting a drug to a particular region of the body for
extended periods of time.
The term "mucoadhesion" was coined for the adhesion of the polymers with the surface of the mucosal layer. Bio
adhesions are a phenomenon in which two materials at least one of which is biological and are held together by
means of interfacial forces. In biological systems, bio adhesion can be classified into 3 types:
1. Adhesion between two biological phases, for example, platelet aggregation and wound healing.
2. Adhesion of a biological phase to an artificial substrate, for example, cell adhesion to culture dishes and bio film
formation on prosthetic devices and inserts.
3. Adhesion of an artificial material to a biological substrate, for example, adhesion of synthetic hydrogels to soft
tissues and adhesion of sealants to dental enamel.
For drug delivery purposes, the term bio adhesion implies attachment of a drug carrier system to a specified
biological location. The biological surface can be epithelial tissue or the mucus coat on the surface of a tissue. If
adhesive attachment is to a mucus coat, the phenomenon is referred to as mucoadhesion / mucoadhesion as the
interaction between a mucin surface and a synthetic or natural polymer. In bio adhesion, the polymer is attached to
the biological membrane.
Advantages of Mucoadhesive Systems
Mucoadhesive systems have three distinct advantages when compared to conventional dosage forms:
1. Readily localized in the region applied to improve and enhance the bioavailability of drugs. For eg. testosterone
and its esters, vasopressin, dopamine, insulin and
gentamycin, etc.
2. Facilitate intimate contact of the formulation with underlying absorption surface. This allows modification of
tissue permeability for absorption of macromolecules. For e.g. peptides and proteins.
3. Prolong residence time of the dosage form at the site of application and absorption to permit once or twice a day
dosing.

26.Classify various mucoadhesive polymers with examples.

27.Explain floating drug delivery system with respect to GRDDS.
Floating Drug Delivery System
Floating drug delivery systems (FDDS) have a bulk density lower than gastric fluids and thus remain buoyant in
stomach for a prolonged period of time, without affecting the gastric emptying rate. While the system floats on
gastric contents, the drug is released slowly at a desired rate from the system. After the release of drug, the residual
system is emptied from the stomach. This results in an increase in gastric retention time and a better control of
fluctuations in plasma drug concentrations. Floating systems can be classified into two distinct categories, (i) Non-
effervescent and (ii) Effervescent systems.
1. Effervescent :
(a) Gas generating systems
(b) Volatile liquid containing systems.
(c)Inflatable gastrointestinal delivery systems.
(d) Intragastric osmotically controlled drug delivery system.
2. Non-Effervescent:
(a) Colloidal gel barrier systems
(b) Alginate beads.
(c) Hollow microspheres.
(d) Microporous compartment system.
1. Effervescent -
(a) Gas Generating Systems:
i) Intra Gastric Single Layer Floating Tablets or Hydrodynamically Balanced System (HBS):
• These are formulated by intimately mixing the CO2 generating agents and the drug within the matrix.
• These have a bulk density lower than gastric fluids and therefore remain floating in the stomach unflattering the
gastric emptying rate for a prolonged period.
• The drug is slowly released at a desired rate from the floating system and after the complete release, the residual
system is expelled from the stomach.
• This leads to an increase in the gastric retention time and a better control over fluctuations in plasma drug
concentration.
ii) Intra Gastric Bilayer Floating Tablets:
These are also compressed tablets and containing two layers i.e.
(i) Immediate release layer (ii) Sustained release layer
(b) Volatile Liquid/Vacuum Containing Systems:
Intragastric Floating Gastrointestinal Drug Delivery System :
• These systems can be made to float in the stomach because of floatation chamber, which may be a vacuum or
filled with air or a harmless gas, while drug reservoir is encapsulated inside a microporous compartment.
(c) Inflatable Gastrointestinal Delivery Systems:
• In these systems, an inflatable chamber is incorporated, which contains liquid ether that evaporates at body
temperature to cause the chamber to inflate in the stomach.
• These systems are fabricated by loading the inflatable chamber with a drug reservoir, which can be a drug,
impregnated polymeric matrix, then encapsulated in a gelatin capsule.
• After oral administration, the capsule dissolves to release the drug reservoir together with the inflatable chamber.
(d) Intragastric Osmotically Controlled Drug Delivery System:
• It is comprised of an osmotic pressure-controlled drug delivery device and an inflatable floating support in a
biodegradable capsule. In the stomach, the capsule quickly disintegrates to release the intragastric osmotically
controlled drug delivery device.
• The inflatable support inside forms a deformable hollow polymeric bag that contains a liquid that vaporizes at
body temperature to inflate the bag.
• The osmotic pressure-controlled drug delivery device consists of two components drug reservoir compartment
and an osmotically active compartment.
• The drug reservoir compartment is enclosed by a pressure responsive collapsible bag, which is impermeable to
vapour and liquid and has a drug delivery orifice.
2. Non-Effervescent
(a) Colloidal Gel Barrier Systems:
• Such systems contain drug with gel forming hydrocolloids meant to remain buoyant on stomach contents.
• These systems incorporate a high level of one or more gel forming highly s wellable cellulose type hydrocolloids.
For e.g. HPMC, NaCMC.
• On coming in contact with gastric fluids forms a viscous core.
• Incorporates H2O and entraps air.
• Density of system falls below 1 gm/cm³. Then it starts floating.
(b) Microporous Membrane System:
Based on the encapsulation of drug reservoir inside a Microporous compartment,
• The peripheral walls of the drug reservoir compartment are completely sealed to prevent any direct contact of the
gastric mucosal surface with the undissolved drug.
• In stomach, the floatation chamber containing entrapped air causes the delivery
system to float over the gastric contents.
• Gastric fluid enters through the apertures, dissolves the drug and carries the dissolved drug for absorption.
(c) Alginate Beads :
• Spherical beads of approximately 2.5 mm in diameter can be prepared by dropping a sodium alginate solution into
aqueous solutions of calcium chloride, causing precipitation of calcium alginate.
• Sodium alginate + Calcium chloride, Calcium alginate + NaCl.
• The beads are then separated and frozen in liquid nitrogen, and freeze dried at -40°C for 24 hours, leading to the
formation of porous system.
• Maintain a floating force of over 12 hours.
(d) Hollow Microspheres:
• Microballoons / hollow microspheres loaded with drugs are prepared by simple solvent evaporation method.
• Commonly used polymers to develop these systems are polycarbonate, cellulose acetate, calcium alginate,
Eudragit S, agar and pectin, etc.
• These systems have capacity to float on acidic dissolution media containing surfactant for about 12 hours invitro.

28.Explain criteria for selection of drug candidate for GRDDS.

29.Write in detail swelling system to achieve GRDSDS.
Swellable Systems -
• A dosage form in the stomach will withstand gastric transit if it is bigger than pyloric sphincter. However, the
dosage form must be small enough to be swallowed, and must not cause gastric obstruction either singly or by
accumulation.
• Thus, their configurations are required to develop an expandable system to prolong gastric retention time (GRT):
1. A small configuration for oral intake.
2. An expanded gastro-retentive form.
3. A final small form enabling evacuation following drug release from the device.
• Thus, gastro-retentivity is improved by the combination of substantial dimension with high rigidity of dosage
form to withstand peristalsis and mechanical contractility of the stomach.
• Unfoldable and swellable systems have been investigated and recently tried to develop an effective gastro-
retentive drug delivery.
• Unfoldable systems are made of biodegradable polymers.
• They are available in different geometric forms like; tetrahedron, ring or planner membrane (4 - label disc or 4 -
limbed cross form) of bioerodible polymer compressed within a capsule which extends in the stomach.
• Swellable systems are also retained in the gastro intestinal tract (GIT) due to their mechanical properties.
• The swelling is usually resulting from osmotic absorption of water and the dosage form is small enough to be
swallowed by the gastric fluid. Expandable systems have some drawbacks like problematical storage of much
easily hydrolysable, biodegradable polymers, relatively short-lived mechanical shape memory for the unfolding
system, most difficult to industrialize and not cost effective.
• Again, permanent retention of rigid, large single-unit expandable drug delivery dosage forms may cause brief
obstruction, intestinal adhesion and gastropathy.

30.Explain bioadhesive-mucoadhesive approach for GRDDS.

31.What is IUD delivery system? Write development of IUDs.
Anatomy of the Uterus
• The uterus is a pear shaped; thick walled, muscular organ suspended in the anterior wall of pelvic cavity.
• It measures normally about 3 inches long and 2 inches wide.
• Fallopian tubes enter its upper portion, one on each side and the lower portion of the uterus projects into the
vagina.
• The uterine cavity is normally triangular in shape and flattened anterio-posteriorly.
The wall of the uterus consists of three layers:
1. Endometrium: It is the inner coat of the uterine wall and is a mucous membrane which consists of epithelium
lining and connective tissue. There are two types of arteries.
(a) Straight arteries: Supplies deeper layer.
(b) Coiled arteries: Supplies superficial layer.
2. Myometrium: It is a thick, muscular middle, layer made up of bundles of interlaced, smooth muscle fibers
embedded in connective tissue. It is subdivided into three ill- defined, interwining muscular layers containing large
blood vessels of uterine walls.
3. Peritoneum: It is external surface of the uterus, which is attached to both sides of the pelvic cavity by blood
ligaments through which the uterine arteries cross.
Intrauterine Devices (IUD's)
• It is the small object that is inserted through the cervix and placed in the uterus to prevent pregnancy.
• A small string hangs down from the IUD into the upper part of the vagina.
• IUD's show pharmacological efficacy for about 1-10 years. They work by changing the lining of the uterus and
fallopian tubes affecting the movements of eggs and sperm and so that fertilization does not occur.
Development of IUD's
• These devices cause more endometrial compression and myometrial distention, leading to uterine cramps,
bleeding and expulsion of IUDS.
• Researchers developed IUDs in past 30 years with the aim to add antifertility agents to more tolerated, smaller
devices, such as T-shaped device, to enhance effectiveness; or antifibrinolytic agents, such as e-aminocaproic acid
and tranexamic acid to larger IUDs to minimize the bleeding and pain.
• Tatum developed a T-shaped device that would work better with the shape of the uterus, which forms a T when
contracted. This reduced side effects significantly.
• Zipper 1968 added contraceptive metals (Cu) and Doyle and Clewe developed Progestin releasing IUD
• This development initiated a new era of R and D for long term IU contraception, leading to generation of recent
IUDs-medicated IUDs.
• Copper bearing IUDs such as Cu-7 and Progesterone releasing IUDs such as Progestasert (approved by FDA in
1976) thus evolved.

32. Describe hormone releasing IUDs.

Intrauterine Devices (IUD's)
• It is the small object that is inserted through the cervix and placed in the uterus to prevent pregnancy.
• A small string hangs down from the IUD into the upper part of the vagina.
• IUD's show pharmacological efficacy for about 1-10 years. They work by changing the lining of the uterus and
fallopian tubes affecting the movements of eggs and sperm and so that fertilization does not occur.
Development of IUD's
• These devices cause more endometrial compression and myometrial distention, leading to uterine cramps,
bleeding and expulsion of IUDS.
• Researchers developed IUDs in past 30 years with the aim to add antifertility agents to more tolerated, smaller
devices, such as T-shaped device, to enhance effectiveness; or antifibrinolytic agents, such as e-aminocaproic acid
and tranexamic acid to larger IUDs to minimize the bleeding and pain.
• Tatum developed a T-shaped device that would work better with the shape of the uterus, which forms a T when
contracted. This reduced side effects significantly.
• Zipper 1968 added contraceptive metals (Cu) and Doyle and Clewe developed Progestin releasing IUD
• This development initiated a new era of R and D for long term IU contraception, leading to generation of recent
IUDs-medicated IUDs.
• Copper bearing IUDs such as Cu-7 and Progesterone releasing IUDs such as Progestasert (approved by FDA in
1976) thus evolved.
Types of IUDs :
1. Non-medicated IUDs
2. Medicated IUDS
1. Non-medicated IUDs: These exert their contraceptive action by producing a sterile inflammatory response in
the Endometrium by its mechanical interaction. These do not contain any therapeutic effect.
For eg. Ring-Shaped IUDs of Stainless Steel, Plastic IUDs, Lippes Loop, Dalkon Shield, Saf-T-Coil.
2. Medicated IUDs: These are capable of delivering pharmacologically active antifertility agents.
For e.g. Copper bearing IUDs, Progesterone releasing IUD.
There are two types of medicated IUDs.
1. Copper bearing IUDs.
2. Hormone releasing IUDS: There are two types:
(a) Progesterone releasing IUD - Progestasert.
(b) Levonorgesterone IUD - Levonorgestrel releasing device - [MIRENA].
Advantages of IUD's :
• It is highly effective, with a 98-99% success rate over five years of IUD use.
• It can be used by almost any woman including nulliparous.
• Its action lasts for ten years if it is not removed inbetween.
• The onset of action is immediate.
• It is suitable for lactating women.
• Fertility returns promptly on discontinuation.
• It can be used by women who are on any type of medication.
• It is not associated with cancer of any organ unlike hormonal contraception.
• It is cost effective.
Disadvantages of IUD's :
• Menorrhagia is a frequent complaint, as are dysmenorrhoea and polymenorrhoea. These are the major reasons for
IUD discontinuation.
• It does not offer any protection against sexually transmitted infections (STIs).
• Expulsion of the IUD may occur especially following or during the periods in the first three months.
• Uterine perforation may occur in 0.1% of women during insertion. This may manifest as lower abdominal pain.
Perforation will require surgical removal.
• There is a higher risk of ectopic pregnancy if conception occurs with an IUD in situ, though pregnancies are very
rare with this method.
• Nausea, Vomiting, Headache and Weight gain are some of the side effects.
Applications of IUD's :
• It is used as a contraceptive to prevent pregnancy.
• It can be suitable for use in Hormone Replacement Therapy.
• It can be safely used in women with heavy bleeding to prevent/control the same.
• In the treatment of fibroids.
33. What are the concepts and approaches of targeted drug delivery systems?
CONCEPTS AND COMPONENTS OF TDDS-
• Targeting of drugs to special cells and tissues of body without becoming a part o systemic circulation is a novel
idea. The drug can be administered in a form such that reaches the receptor site in sufficient concentration without
disturbing an extraneous tissue cell
Such products are prepared by considering:
• Specific properties of target cells.
• Nature of markers or transport corners or vehicles which convey drugs to specific receptors.
• Ligands and physically modulated compounds.
1.Target cell : Target cell could be described as a cell or group of cells in minority, identified to be in the need of
treatment.
• Two distinctive cellular elements present on the surface of the target cell are considered in designing the carriers
for targeting via:
• Cell surface antigens exploited in generating cell surface and non-selective antibodies.
• Cell surface and receptors which recognize and internalize the macromolecular ligands associated carriers.
Types of Targets:
• Cells, in vitro for genome grafting or manipulation of DNA.
• Accessible anatomical compartment i.e., peritoneal cavity cerebral vesicles, pleural cavity lungs, lymphatics.
• Macrophages and other phagocytic cells including kuffer cells, tissue macrophages and blood macrophages or
monocytes of MPS.
• Non-phagocytic cells and RES including liver endothelial cells.
• Lymphocytes and antigens present in cells.
2. Carriers: Carrier is one of the important entities essentially required for effective transportation of the loaded
drug(s). They are vectors, which sequester, retain drug and transport or deliver it into the vicinity of target cells.
• Carriers can do so either through an ability inherent or acquired through structural modification to interact
selectively with biological target or otherwise they are engineered to release the drug in the proximity of the target
of cell line that demand optimal pharmacological action.
Types of Carriers:
(a) Physical markers for e.g. Liposomes, microspheres.
(b) Physiological markers. For eg. Monoclonal antibodies, erythrocytes. (c) Chemical markers such as prodrugs.
Characteristics:
• It must be able to cross anatomical barriers.
• The target cells must recognize it specifically and selectively.
• The linkage of the drug and directing unit should be stable in plasma, intestinal and other biological fluids.
• After recognition and internalization, the carrier system should release the drug moiety inside the target organs,
tissues and cells.
• Carrier should be non-toxic, non-immunogenic and biodegradable.
3. Ligands : The ligands confer recognition and speficity upon carrier/vector and lend them to approach the
respective target and deliver the drug. For e.g. Antibodies, polypeptides,endogenous hormones, etc.
APPROACHES
There are mainly two approaches-
(a) Chemical modification of the parent compound to a derivative which is activated only at the target site.
(b) Utilization of carriers such as; liposomes, microspheres, nanoparticles, monoclonal antibodies, cellular carriers
(erythrocytes and lymphocytes), macromolecules, platelets to direct the drug at its site of action.
(i) Prodrug approach
(ii) Chemical delivery approach
(iii) More approaches
• Active targeting (ligand mediated targeting).
• Passive targeting (natural targeting).
• Physical targeting.
• Chemical targeting.
(i) Prodrug Approach: A product is an active chemical derivative of a parent compound
that inactivated predictably into active drug species.
(ii) Chemical Approach: It involves transformation of the active drug by synthetic means into inactive derivatives
which when placed in the body will undergo several predictable enzymatic transformations principally at its site of
action. This approach has proven to be successful in delivery of drugs to the eye, brain and testis.
(iii) More Approaches:
(a) Active Targeting: In active targeting, the natural disposition pattern of a carrier is modified to target specific
organs, tissues or attachment of cells, specific ligand and monoclonal antibodies. It adopts modified drug carrier
molecules capable of recognizing and interacting with a specific cell, tissues or organs in the body. Modification of
the carrier system includes a change in molecular size, alteration of specific antibodies or attachment of cells
receptor specific ligands.
(b) Passive Targeting: This refers to the natural distribution pattern of the carrier in vivo. Their particle size,
shape, surface characteristics and the surface charge and particle numbers largely determine the disposition of the
carrier. Hence it is possible to target the lungs and reticules endothermic system passives. For e.g. Different regions
of GI tract, eye, nose.
(c) Physical Targeting: It refers to drugs delivery system that release a drug only when exposed to specific
microenvironment such as change in pH or temperature or the use of an external magnetic field. For e.g. In the
presence of certain serum protein (lipoprotein), unilamellar liposome can be designed to release their pay loads
efficiently at their liquid crystalline phase temperature.
(d) Chemical Targeting: A prodrug is a pharmacologically inert form of an active drug that must undergo
transformation to parent compound in vivo by either a chemical or enzymatic reaction to exert its therapeutic
effects. Prodrugs are designated to alter the absorption, distribution and metabolism of the parent compound,
thereby increase its beneficial effects and decrease its toxicity. They are also used to avoid an unpleasant taste and
odour of the parent compound. For e.g. Epinephrine to eyes in the treatment of glaucoma. Acyclovir an antiviral
drug in herpes infection.
34. What is mean by monoclonal antibodies? Give its applications.
MONOCLONAL ANTIBODIES
• Monoclonal antibodies are identical immunoglobulins, generated from a single B-Cell clone. These antibodies
recognize unique epitopes or binding sites on a single antigen. Derivation from a single B-Cell clones and
subsequent targeting of a single epitome is what differentiates monoclonal antibodies from polyclonal antibodies.
• Polyclonal antibodies are antibodies that are derived from different cell lines. They differ in amino acid
sequences.
Advantages of Monoclonal Antibodies -
• Though expensive mAB are cheaper to develop than conventional drugs because it is based on tested technology.
• Side effects can be treated and reduced by using mice-human hybrid cells or by using fractions of antibodies.
• They bind to specific diseased or damaged cells needing treatment.
• They treat a wide range of conditions.
Disadvantages of Monoclonal Antibodies-
• Time consuming method as it requires on an average of 6-9 months.
• It is very expensive and needs considerable efforts to produce them.
• Small peptide and fragment antigens may not be good antigens-monoclonal antibody may not recognize the
original antigen.
• Hybridoma culture may be subject to contamination.
• System is only well developed for limited animal and not for other animals.
• More than 99% of the cells do not survive during the fusion process-reducing the range of useful antibodies that
can be produced against an antigen.
• It is every possible that immunogenicity can be generated.
Preparation -
• Monoclonal Antibodies Products or (mAB) is produced by cells lines or clones obtained from the immunized
animals with the substances. Cell lines are produced by fusing B- cells from the immununized animal with
myeloma cells.
• To produce the desired mAB, the cells must be grown in either of two ways:
1. By Injection into the peritoneal cavity of a suitably prepared mouse (in vivo method).
2. In vitro Tissue Culture.
• The vitro tissue culture is the method used when the cells are placed in culture outside the mouse, the mouse's
body in flask.
Applications of Monoclonal Antibodies
1. Diagnostic Applications
(a) Biochemical analysis
(b) Diagnostic imaging
2. Therapeutic Applications
(a) Direct use of mAB's as therapeutic agents
(b) mAB's as targeting agents
3.Protein Purification
1. Diagnostic Applications:
(a) Biochemical Analysis:
1. It is used in the Radioimmuno assays (RIA) and Enzyme linked Immunosorbent
assays (ELISA) in the Laboratory.
2. These assays measure the circulating concentration of Hormones (Insulin, HCG- Human Chorionic
Gonadotropin, Growth Hormone. Progesterone, Thyroxine, Triiodothyronine. Thyroid Stimulating Hormone)
several other tissue and cell oducts (Blood Group antigen, Blood clotting factors, interferon's, interleukins, tumor
markers).
Example:
(i) Pregnancy by detecting the urinary levels of HCG
(ii)Hormonal disorders analysis of thyroxine, triiodothyroxine.
(iii) Cancer estimation of plasma carcinoembryonic antigen in colorectal cancers and prostate specific antigen for
prostate cancer
(b) Diagnostic Imaging:
• Radiolabelled in imaging of diseases and this technique is referred to as
Immunoscintigraphy. Radioisotope commonly used for labelling mAB are Iodine- 131 and technetium-99. The
mAB tagged with radioisotope are injected intravenous into the patients.
• These mABS localize at specific sites (say a tumor) which can be detected by Imaging the Radioactivity.
• Myocardial Infarction, DVT, Atherosclerosis, etc.
2. Direct Use of mAB's as Therapeutic Agents:
• In destroying disease-causing organisms - mAB's promote efficient opsonisation of Pathogenic organisms (by
coating with antibody) and enhance Phagocytosis.
• In Immunosuppression of Organ Transplantation. In the normal medical practice,
immunosuppessive drugs such as cyclosporine and prednisolone are administered to overcome the rejection of
organ transplantation. Now-a-day mAB's specific to T-Lymphocyte surface antigen are being used for this purpose
3. Protein Purification:
• mAB's can be produced for any protein so the produced mAB's purification is required against which it is raised.
• mAB's columns can be prepared by coupling them to cyanogen bromide activated sepharose (chromatographic
matrix). The immobilized mAB's in this manner are very useful for the purification of Proteins by immunoaffinity
method.
• There are certain advantages of using mAB's for protein purification. These include the specificity of the mAB to
bid to the desired protein, very efficient elution from the chromatographic column and high degree of purification.

35. What are intra ocular barriers? Explain any two methods to overcome intra ocular barriers.
36. Explain ocular formulations and ocuserts.
1. Conventional Delivery Systems
(a) Eye drops
(b) Ointments and Gels
(c) Ocuserts and Lacriserts
2. Vesicular Systems
(a) Liposomes
(b) Niosomes and Discomes (Giant Niosomes) 3.
3. Controlled Delivery Systems
(a) Implants
(b) Iontophoresis
(c) Dentrimer
(d) Microemulsion
(e) Nanosuspension
(f) Microneedle
(g) Mucoadhesive Polymers
Classification of Inserts
1. Non-Erodible Inserts
(a) Ocusert
(b) Contact Lens
2. Erodible Inserts
(a) Lacriserts
(b) SODI
(c) Mindisc
Ocuserts: It is a flat, flexible, elliptical device designed to be placed in the inferior cul- de-sac between the sclera
and eyelid which releases Pilocarpine continuously at a steady state for 7 days.
It comprises of 3 layers:
1. Outer Layer: Ethylene vinyl acetate copolymer layer.
2. Inner Layer: Pilocarpine gelled with alginate main polymer.
3. A retaining ring of EVA impregnated with titanium dioxide. Example: Pilo 20 (20 mg/hr), Pilo 40 (40 mg/hr).

37. Give difference between nasal and pulmonary drug delivery system.
38. What is nasopulmonary drug delivery system? Give its advantages and disadvantages.
Applications Of Nasal Drug Delivery System :
1. Delivery of non-peptide pharmaceuticals. For e.g. Adrenal corticosteroids, Hormones like Progesterone,
Vitamin, Cardiovascular drugs, etc.
2. Delivery of peptide-based pharmaceuticals. For e.g. Insulin, Calcitonon, Pituitary hormones.
3. Delivery of diagnostic agents. For e.g. Phenolsulfonphthalein is used to diagnose kidney function.
4. Delivery of vaccines through nasal route. For e.g. Anthrax and Influenza are treated by using the nasal vaccines.
5. Delivery of drugs to brain through nasal cavity. For e.g. Parkinson's disease, Alzheimer's disease.
Advantages Of Nasal Drug Delivery System
1. Drug degradation that is observed in the gastrointestinal tract is absent.
2. Hepatic first pass metabolism is avoided.
3. Rapid drug absorption and quick onset of action can be achieved.
4. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other
approach.
5. The nasal bioavailability for smaller drug molecules is good.
6. Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery.
7. Studies so far carried out indicate that the nasal route is an alternate to parenteral route, especially, for protein
and peptide drugs.
8. Convenient for the patients, especially for those on long term therapy, when compared with parenteral
medication.
9. Drugs possessing poor stability in G.I.T. fluids are given by nasal route.
10. Polar compounds exhibiting poor oral absorption may be particularly suited for this route of delivery.
Disadvantages of Nasal Drug Delivery System
1. The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly
established.
2. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal
irritation.
3. Nasal cavity provides smaller absorption surface area when compared to GIT.
4. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the
substance and from constituents added to the dosage form.
5. Certain surfactants used as chemical enhancers may disrupt and even dissolve membrane in high concentration.
6. There could be a mechanical loss of the dosage form into the other parts of the respiratory tract like lungs
because of the improper technique of administration.
ADVANTAGES OF PULMONARY DRUG DELIVERY SYSTEM
1. It is needle free pulmonary delivery.
2. It requires low and fraction of oral dose.
3. Pulmonary drug delivery having very negligible side effects since rest of body is not exposed to drug.
4. Onset of action is very quick with pulmonary drug delivery.
5. Degradation of drug by liver is avoided in pulmonary drug delivery.
DISADVANTAGES OF PULMONARY DRUG DELIVERY SYSTEM
1. Stability of drug in-vivo.
2. Transport.
3. Targeting specificity.
4. Drug irritation and toxicity.
5. Immunogenicity of proteins.
6. Drug retention and clearance.
The formulation approaches are as follows:
• Pulmonary delivered drugs are rapidly absorbed except large macromolecules drugs, which may yield low
bioavailability due to enzymatic degradation and/or low mucosal permeability.
• Pulmonary bioavailability of drugs could be improved by including various permeation enhancers such as;
surfactants, fatty acids and saccharides, chelating agents and enzyme inhibitors such as protease inhibitors.
• The most important issue is the protein stability in the formulation: the dry powder formulation may need buffers
to maintain the pH, and surfactants such as; Tween to reduce any chance of protein aggregation. The stabilizers
such as; sucrose are also added in the formulation to prevent denaturation during prolonged storage.
• Pulmonary bioavailability largely depends on the physical properties of the delivered protein and it is not the
same for all peptide and protein drugs.
• Insulin lisomes are one of the recent approaches in the controlled release aerosol The preparations. Intratracheal
delivery of insulin liposomes (dipalmitoyl phosphatidylcholine: cholesterol, 7: 2) have significantly enhanced the
desired hypoglycaemic effect.

39. Write note on Copper T.

40. Enlist and explain nasal formulations.
The Components of the Nasal Formulations:
• Drug Terbutaline sulphate. -
• Viscosifying Agents - Hydroxypropyl cellulose
• Solubilizers - Glycol, Alcohol, Cyclodextrins.
• Surfactants SLS, Polyacrylic acid.
• Bio-adhesive Polymers - Methylcellulose, Carboxymethylcellulose
• Preservatives - Parabens, Benzalkonium chloride.
• Antioxidants - Sodium metabisulphite.
Nasal Formulations :
1. Nasal Gels: These are highly viscous, thickened solutions or suspensions. Theses have
following advantages:
• Reduction of post nasal drip due to high viscosity.
• Reduction of taste impact due to reduced swallowing.
• Reduction of anterior leakage of the formulation.
These are useful as there is reduction of irritation by using emollient excipients.
2. Nasal Drops: These are one of the simple and convenient systems developed for nasal delivery. The main
disadvantage of this system is the lack of the dose precision and therefore nasal drops may not be suitable for
prescription products. It has been reported that nasal drops deposit Human Serum albumin in the nostrils more
efficiently than nasal sprays.
3. Nasal Ointments: These are translucent, homogenous, viscous, semi-solid preparations intended to be instilled
in the nose. Due to their viscosity they will not ooze out of the nose.
4. Nasal Sprays: Solution and Suspension formulations can be formulated into nasal sprays, Due to the availability
of metered dose pumps and actuators, a nasal spray can deliver an exact dose from 25-200 µm. The particle size
and morphology (for suspensions) of the drug and viscosity of the formulation determine the choice of pump and
actuator assembly.
5. Nasal Powder: This dosage form may be developed if solution and suspension dosage forms cannot be
developed. For e.g. due to lack of drug stability.
The advantages of the nasal powder dosage form are the absence of preservative and superior stability
of the formulation. However, the suitability of powder formulation is dependent on the solubility, particle size,
aerodynamic properties and nasal irritancy of the active drug and/or excipients. Local application of drug is another
advantage of this system.
6. Liposomes: Liposomal nasal solutions can be formulated as drug alone or in combination with pharmaceutically
acceptable excipients. They are administered to the respiratory tract as an aerosol or solution for a nebulizer, or as a
microfine powder for insufflations, above or in combination with an inert carrier such as; lactose, the particles of
the formulation have diameters of less than 50 microns.
7. Microspheres: The main usefulness of specialized system in designed nasal products is that, it prolongs the
contact with the nasal mucosa. The microspheres in their powder form swell in contact with nasal mucosa to form a
gel and controls the rate of clearance from the nasal cavity. Thus, increases the absorption and bioavailability by
adhering to the nasal mucosa and increases the nasal residence time of drug. The ideal microsphere particle size
requirement for nasal delivery should range from 10-50 μm as smaller particles.
Applications Of Nasal Drug Delivery System :
1. Delivery of non-peptide pharmaceuticals. For e.g. Adrenal corticosteroids, Hormones like Progesterone,
Vitamin, Cardiovascular drugs, etc.
2. Delivery of peptide-based pharmaceuticals. For e.g. Insulin, Calcitonon, Pituitary hormones.
3. Delivery of diagnostic agents. For e.g. Phenolsulfonphthalein is used to diagnose kidney function.
4. Delivery of vaccines through nasal route. For e.g. Anthrax and Influenza are treated by using the nasal vaccines.
5. Delivery of drugs to brain through nasal cavity. For e.g. Parkinson's disease, Alzheimer's disease.
Advantages Of Nasal Drug Delivery System
1. Drug degradation that is observed in the gastrointestinal tract is absent.
2. Hepatic first pass metabolism is avoided.
3. Rapid drug absorption and quick onset of action can be achieved.
4. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other
approach.
5. The nasal bioavailability for smaller drug molecules is good.
6. Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery.
7. Studies so far carried out indicate that the nasal route is an alternate to parenteral route, especially, for protein
and peptide drugs.
8. Convenient for the patients, especially for those on long term therapy, when compared with parenteral
medication.
9. Drugs possessing poor stability in G.I.T. fluids are given by nasal route.
10. Polar compounds exhibiting poor oral absorption may be particularly suited for this route of delivery.
Disadvantages of Nasal Drug Delivery System
1. The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly
established.
2. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal
irritation.
3. Nasal cavity provides smaller absorption surface area when compared to GIT.
4. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the
substance and from constituents added to the dosage form.
5. Certain surfactants used as chemical enhancers may disrupt and even dissolve membrane in high concentration.
6. There could be a mechanical loss of the dosage form into the other parts of the respiratory tract like lungs
because of the improper technique of administration.
The different approaches:
1. Prodrug Approach: The absorption of peptides like angiotensin II, Bradykinin, Vasopressin and Calcitonin are
improved when prepared into enamine derivatives.
2. Structural Modification: Chemical modification of Salmon Calcitonin to ecatonin (C-N bond replaces the S-S
bond) showed better bioavailability.
3. Particulate drug Delivery:
(i) Microspheres, Nanoparticles and Liposomes.
(ii) Nasal Enzyme Inhibitors.
• Peptides and Proteases.
• Triptin Aprotinin, Borovaline, Amastatin, Betaststin and Boroleucin inhibitors.
41. What is inflatable and gastroadhesive systems in GRDDS. Give its applications.
A. Inflatable Gastrointestinal Delivery Systems : In these systems, an inflatable chamber is incorporated, which
contains liquid ether that evaporates at body temperature to cause the chamber to inflate in the stomach.
• These systems are fabricated by loading the inflatable chamber with a drug reservoir, which can be a drug,
impregnated polymeric matrix, then encapsulated in a gelatin capsule.
• After oral administration, the capsule dissolves to release the drug reservoir together with the inflatable chamber.
• The inflatable chamber automatically inflates and retains the drug reservoir compartment in the stomach.
• The drug continuously released from the reservoir into the gastric fluid.
B. Gastroadhesive System : The gastroadhesive system focuses on using the adhesive properties of certain
polymers to achieve gastroretention. These polymers possess adhesive properties that enable them to adhere to the
gastric mucosa (the lining of the stomach). By adhering to the stomach wall, the drug delivery system can remain in
the stomach for an extended period of time, ensuring controlled release and improved drug absorption.
• There are several mechanisms through which gastroadhesive systems work:
1. Mucoadhesion: The polymers in the drug delivery system interact with the mucus layer of the stomach, forming
adhesive bonds. This interaction allows the system to adhere to the gastric mucosa and resist forces that would
normally push it towards the intestine.
2. Swelling: Some polymers used in gastroadhesive systems have the ability to swell upon contact with gastric
fluids. The swelling enhances the adhesion of the system to the stomach wall, preventing its passage through the
pyloric sphincter (the opening between the stomach and the small intestine).
3. Expansion: Certain drug delivery systems are designed to expand upon contact with gastric fluids. This
expansion creates a larger physical size, making it difficult for the system to pass through the pyloric sphincter and
promoting gastroretention.
• The gastroadhesive system can be formulated in various dosage forms such as tablets, capsules, or floating
systems. The choice of polymer and formulation technique depends on factors like drug characteristics, desired
drug release profile, and patient requirements.
• Overall, the gastroadhesive system in gastroretentive drug delivery aims to improve drug bioavailability, reduce
dosing frequency, and enhance therapeutic efficacy by prolonging the residence time of drugs in the stomach
through adhesive interactions with the gastric mucosa.
• Applications of Gastroadhesive Systems
1. Enhanced Bioavailability : The bioavailability of riboflavin GRDF is significantly enhanced in comparison to
the administration of non-GRDF polymeric formulations.
• There are several different processes, related to absorption and transit of the drug in the gastrointestinal tract, that
act concomitantly to influence the magnitude of drug absorption.
2. Sustained Drug Delivery/Reduced Frequency of Dosing : For drugs with relatively short biological half-life,
sustained and slow input from GRDF may result in improved pharmacokinetics and reduced dosing frequency.
• This feature is associated with improved patient compliance and thereby improves therapy.
3. Targeted Therapy for Local Ailments in the Upper GIT : The prolonged and sustained administration of the
drug from GRDF to the stomach may be advantageous for local therapy in the stomach and small intestine.
• By this mode of administration, therapeutic drug concentrations may be attained locally while systemic
concentrations, following drug absorption and distribution, are minimal.
4. Reduced Fluctuations of Drug Concentration : Continuous input of the drug following GRDF administration
produces blood drug concentrations within a narrower range compared to the immediate release dosage forms.
• Thus, fluctuations in drug effects are minimized and concentration dependent adverse effects that are associated
with peak concentrations can be prevented.
• This feature is of special importance for drugs with a narrow therapeutic index.

42.What is transmucosal permeability? Give formulation considerations of buccal drug delivery systems.
Transmucosal permeability refers to the ability of a substance to pass through a mucous membrane. Mucous
membranes are found in various parts of the body, such as the respiratory tract, gastrointestinal tract, and
genitourinary tract. These membranes are composed of epithelial cells that are specialized for absorption and
secretion.
When a substance is administered transmucosally, it bypasses the gastrointestinal tract and is absorbed directly into
the bloodstream through the mucous membrane. This route of administration can provide several advantages, such
as faster onset of action, avoidance of first-pass metabolism, and improved patient compliance.
• Buccal Delivery System : Buccal drug delivery systems interact with the mucus layer covering the mucosal
epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption.
The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require
increased duration of stay in GIT. Thus, buccal dosage forms are advantageous in increasing the drug plasma
concentrations and also therapeutic activity.
Formulation Design : Pharmaceutical considerations: Great care needs to be exercised while developing a safe
and effective buccal adhesive drug delivery device. Factors influencing drug release and penetration through buccal
mucosa are organoleptic factors and effects of additives used to improve drug release pattern and absorption, the
effects of local drug irritation caused at the site of application are to be considered while designing a formulation.
1. Physiological Considerations : Physiological considerations such as; texture of buccal mucosa, thickness of the
mucus layer, its turn over time, effect of saliva and other environmental factors are to be considered in designing
the dosage forms.
For e.g. Saliva contains moderate levels of esterases, carbohydrases, and phosphatases that may degrade certain
drugs. Although saliva secretion facilitates the dissolution of drug, involuntary swallowing of saliva also affects its
bioavailability
2. Pharmacological Considerations : Drug absorption depends on the partition coefficient of the drugs. Generally,
lipophilic drugs absorb through the transcellular route, whereas; hydrophilic drugs absorb through the paracellular
route. Chemical modification may increase drug penetration through buccal mucosa. Residence time and local
concentration of the drug in the mucosa, the amount of drug transported across the mucosa into the blood are the
responsible factors for local or systemic drug delivery. Optimization by a suitable formulation design fastens drug
release from the dosage form taken up by the oral mucosa.
43.Explain the concept of implants and osmotic pump.
1. Implant : an implant refers to a small device or formulation that is designed to be placed inside the body to
deliver therapeutic substances, such as drugs or hormones, over an extended period of time. The implant serves as a
reservoir or depot for the drug, gradually releasing it into the surrounding tissues or bloodstream at a controlled
rate.
• The concept behind an implant in a novel drug delivery system is to provide a sustained and controlled release of
medication, eliminating the need for frequent dosing or injections. This offers several advantages over conventional
drug delivery methods, such as oral tablets or injections, which often result in fluctuating drug levels in the body.
• Implants can be made from a variety of materials, including biocompatible polymers, metals, or even biological
tissues. These materials are carefully selected based on their compatibility with the body, stability of the drug
within the implant, and ability to release the drug in a controlled manner.
• The drug is typically loaded into the implant either as a solid or in a dissolved or dispersed form within a polymer
matrix. The choice of drug formulation depends on factors such as drug stability, solubility, and desired release
kinetics. The implant may also contain additional components, such as permeation enhancers or rate-controlling
membranes, to further modulate the drug release profile.
• Once the implant is placed in the body, the drug is released through various mechanisms. These mechanisms can
include diffusion of the drug through the implant matrix, erosion or degradation of the implant material, or a
combination of both. The release rate can be tailored by adjusting the properties of the implant, such as the polymer
composition, drug loading, or implant size and shape.
• The benefits of implantable drug delivery systems include improved patient compliance, reduced side effects, and
enhanced therapeutic efficacy. By maintaining a consistent drug concentration within the desired target area,
implants can provide a more sustained and prolonged therapeutic effect compared to traditional dosing regimens.
Additionally, implants can be designed to be easily removable or replaceable, allowing for flexibility in treatment.
• Implantable drug delivery systems have found applications in various medical fields, including contraception,
hormone replacement therapy, pain management, and treatment of chronic conditions such as diabetes or cancer.
Ongoing research and development in this area continue to advance the design and functionality of implantable
devices, leading to improved patient outcomes and quality of life.
2. Osmotic Pump : An osmotic pump is a type of drug delivery system that is designed to deliver a drug at a
controlled and predetermined rate over an extended period of time. It utilizes the principle of osmosis to release the
drug from the system.
• The osmotic pump consists of a drug reservoir, a semi-permeable membrane, and an osmotic core. The drug
reservoir contains the drug formulation, which can be in the form of a solid, liquid, or suspension. The semi-
permeable membrane separates the drug reservoir from the osmotic core. The osmotic core contains an osmotic
agent, typically a water-soluble salt or sugar, that generates an osmotic pressure gradient when exposed to water.
• When the osmotic pump is placed in an aqueous environment, such as the gastrointestinal tract, water permeates
through the semi-permeable membrane into the osmotic core. This creates a pressure inside the osmotic core, which
then pushes the drug solution or suspension out of the system through a delivery orifice.
• The rate of drug delivery from the osmotic pump is primarily controlled by the permeability of the semi-
permeable membrane and the osmotic pressure generated by the osmotic core. The semi-permeable membrane is
designed to allow water to pass through but prevents the passage of drug molecules or large particles. As water
enters the osmotic core, it dissolves the osmotic agent, creating a concentrated solution and generating an osmotic
pressure. This pressure pushes the drug solution or suspension out of the system at a controlled rate.
• The advantage of using an osmotic pump in drug delivery is that it provides a constant and predictable release of
the drug over an extended period. This helps maintain therapeutic drug levels in the body, reducing the frequency
of drug administration and improving patient compliance. Additionally, the system is independent of physiological
factors, such as pH or enzyme activity, which can affect drug release from other drug delivery systems.
• Osmotic pumps have been used in various applications, including oral, transdermal, and implantable drug
delivery systems. They have been particularly useful for drugs that require a sustained release profile or those with
narrow therapeutic windows. The design of osmotic pumps can be tailored to meet the specific requirements of
different drugs, allowing for personalized and optimized drug delivery.

44.Write a note on liposomes.

Liposomes
• Liposomes are concentric bi-layered vesicles in which an aqueous volume is entirely enclosed by a membranous
lipid bilayer mainly composed of natural or synthetic phospholipids.
• Liposomes are microscopic spheres made from fatty materials, predominantly phospholipids.
• Liposomes are made up of one or more concentric lipid bilayers, and range in size from 50 nanometers to several
micrometers in diameter.
Structural Components of Liposomes
The main components of liposomes are:
1. Phospholipids
2. Cholesterol
1. Phospholipids : Phospholipids are the major structural components of biological membranes. The most common
phospholipid used in liposomal preparation is phosphatidylcholine (PC). Phosphatidylcholine is an amphipatic
molecule containing:
• A hydrophilic polar head group, phosphocholine.
• A pair of hydrophobic acyl hydrocarbon chains.
• A glycerol bridge.
Molecules of phosphatidylcholine are not soluble in water. In aqueous media, they align themselves
closely in planar bilayer sheets in order to minimize the unfavourable action between the bulk aqueous phase and
the long hydrocarbon fatty chain. Then the sheets fold on themselves to form closed sealed vesicles. There are
several phospholipids that can be used for the liposome preparation such as Dilaurylphosphotidylcholine (DLPC).
Dimyristoylphosphotidyl choline (DMPC), Dipalmitoyl phosphotidyl choline (DPPC), Distearoylphosphotidyl
choline (DSPC), Dioleolylphosphotidylcholine (DOPC). Dilaurylphosphotidyl ethanolamine (DLPE),
Dimyristoylphosphotidyl ethanolamine (DMPE), Distearoylphosphotidyl ethanolamine (DSPE), Dioleoyl
phosphotidyl ethanolamine (DOPE), Dilaurylphosphotidyl glycerol (DLPG), Distearoylphosphotidyl serine
(DSPS).
2. Cholesterol : The role of cholesterol in formulation of liposomes was given below:
1. Incorporation of sterols in liposome bilayer produces major changes in the preparation of these membranes.
2. Cholesterol itself does not form a bilayer structure.
3. However, cholesterol acts as a fluidity buffer. Cholesterol itself does not form a bilayer structure.
4. However, Cholesterol acts as a fluidity buffer. It makes the membrane less ordered and slightly more permeable
below the phase transition and makes the membrane more ordered and stable above the transition. It can be
incorporated into phospholipid membranes in very high concentration up to 1:1 or even 2:1 molar ratios of
cholesterol to phospholipids.
• Advantages of Liposomes :
1. Provides selective passive targeting to tumor tissues (liposomal doxorubicin).
2. Increases efficacy and therapeutic index.
3. Increased stability via encapsulation.
4. Reduced toxicity of the encapsulated agent.
5. Site avoidance effect.
6. Improved pharmacokinetic effect (reduced elimination, increased circulating life time).
7. Flexibility to couple with site specific ligands to achieve active targeting.
• Disadvantages of Liposomes :
1. Production cost is high.
2. Leakage and fusion of encapsulated drug/molecules.
3. Sometimes phospholipids undergo oxidation and hydrolysis like reaction.
4. Short half life.
5. Low solubility.
45.Write a note on monoclonal antibodies.
Monoclonal Antibodies
• Monoclonal antibodies are identical immunoglobulins, generated from a single B-Cell clone. These antibodies
recognize unique epitopes or binding sites on a single antigen. Derivation from a single B-Cell clones and
subsequent targeting of a single epitome is what differentiates monoclonal antibodies from polyclonal antibodies.
• Polyclonal antibodies are antibodies that are derived from different cell lines. They differ in amino acid
sequences.
Characters of Monoclonal Antibodies
Monoclonal Antibodies (mAB) are single type of antibodies that are identical and directed against a specific
epitope (antigen, antigenic determinant) and are produced by B-Cell clones of a single parent or a single hybridoma
cell line.
A hybridoma cell line is formed by the fusion of one B-cell lymphocyte with a myeloma cell.
Some myeloma cell synthesizes single mAB antibodies naturally.
Advantages of Monoclonal Antibodies
• Though expensive mAB are cheaper to develop than conventional drugs because it is based on tested technology.
• Side effects can be treated and reduced by using mice-human hybrid cells or by using fractions of antibodies.
• They bind to specific diseased or damaged cells needing treatment. They treat a wide range of conditions.
Disadvantages of Monoclonal Antibodies
• Time consuming method as it requires on an average of 6-9 months.
• It is very expensive and needs considerable efforts to produce them.
• Small peptide and fragment antigens may not be good antigens-monoclonal antibody may not recognize the
original antigen.
• Hybridoma culture may be subject to contamination.
• System is only well developed for limited animal and not for other animals.
• More than 99% of the cells do not survive during the fusion process-reducing the range of useful antibodies that
can be produced against an antigen.
• It is every possible that immunogenicity can be generated.
Preparation
• Monoclonal Antibodies Products or (mAB) is produced by cells lines or clones obtained from the immunized
animals with the substances. Cell lines are produced by fusing B- cells from the immununized animal with
myeloma cells.
• To produce the desired mAB, the cells must be grown in either of two ways:
1. By Injection into the peritoneal cavity of a suitably prepared mouse (in vivo method).
2. In vitro Tissue Culture.
• The vitro tissue culture is the method used when the cells are placed in culture outside the mouse, the mouse's
body in flask.
Practical Steps for Production
• Immunize animal.
• Isolate spleen cells (containing antibody - produced B-cell).
• Fuse spleen cells with myeloma cells (using PEG). Allow infused B-cells to die.
• Add aminopterin to culture and kill unfused myeloma cells.
• Clone remaining cells (place 1 cell/wall and allow each cell to grow into a clones of cell).
• Screen supernatant of each clone for presence of desired antibody.
• Grow chosen clone of cells in tissue culture indefinitely.
• Harvest antibody from the culture.
Applications of Monoclonal Antibodies
1 Diagnostic Applications
(a) Biochemical analysis
(b) Diagnostic imaging
2. Therapeutic Applications
(a) Direct use of mAB's as therapeutic agents
(b) mAB's as targeting agents
3. Protein Purification
1. Diagnostic Applications:
(a) Biochemical Analysis:
1. It is used in the Radioimmuno assays (RIA) and Enzyme linked Immunosorbent assays (ELISA) in the
Laboratory.
2. These assays measure the circulating concentration of Hormones (Insulin, HCG- Human Chorionic
Gonadotropin, Growth Hormone, Progesterone, Thyroxine, Triiodothyronine, Thyroid Stimulating Hormone)
several other tissue and cell products (Blood Group antigen, Blood clotting factors, interferon's, interleukins, tumor
markers).
Example:
(i) Pregnancy by detecting the urinary levels of HCG.
(ii) Hormonal disorders analysis of thyroxine, triiodothyroxine.
(iii) Cancer estimation of plasma carcinoembryonic antigen in colorectal cancers and prostate specific antigen for
prostate cancer.
(b) Diagnostic Imaging:
• Radiolabelled in imaging of diseases and this technique is referred to as Immunoscintigraphy. Radioisotope
commonly used for labelling mAB are Iodine- 131 and technetium-99. The mAB tagged with radioisotope are
injected intravenous into the patients.
• These mABs localize at specific sites (say a tumor) which can be detected by imaging the Radioactivity.
• Myocardial Infarction, DVT, Atherosclerosis, etc.
2. Direct Use of mAB's as Therapeutic Agents:
• In destroying disease-causing organisms - mAB's promote efficient opsonisation of Pathogenic organisms (by
coating with antibody) and enhance Phagocytosis.
• In Immunosuppression of Organ Transplantation: In the normal medical practice, immunosuppessive drugs such
as cyclosporine and prednisolone are administered to overcome the rejection of organ transplantation. Now-a-days
mAB's specific to T-Lymphocyte surface antigen are being used for this purpose.
3. Protein Purification:
• mAB's can be produced for any protein so the produced mAB's purification is required against which it is raised.
• mAB's columns can be prepared by coupling them to cyanogen bromide activated sepharose (chromatographic
matrix). The immobilized mAB's in this manner are very useful for the purification of Proteins by immunoaffinity
method.
• There are certain advantages of using mAB's for protein purification. These include the specificity of the mAB to
bid to the desired protein, very efficient elution from the chromatographic column and high degree of purification.
Long answer questions (10marks)
1. Explain the approaches involved in the design of controlled drug delivery systems.
2. Describe various physicochemical and biological factors to be considered in selection of a drug candidate for
controlled delivery formulations.
3. Write the concept of controlled drug delivery systems. Explain the approaches for the controlled release
formulations based on diffusion.
4. Write the concept of controlled drug delivery systems. Explain the approaches for the controlled release
formulations based on dissolution.
5. Write the concept of controlled drug delivery systems. Explain the approaches for the controlled release
formulations based on ion exchange technique.
6. Define microencapsulation. Write the applications of microencapsulation. Explain Coacervation phase
separation technique.
Microencapsulation is a process that involves enclosing tiny particles or droplets of one substance within a
protective shell made of another material.
• Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers having a
particle size ranging from 1-1000 μm. The range of Techniques for the preparation of microspheres offers a variety
of opportunities to control aspects of drug administration and enhance the therapeutic efficacy of a given drug.
• It is the reliable means to deliver the drug to the target site with specificity, if modified, and to maintain the
desired concentration at the site of interest. It also has advantage over liposomes as it is physico-chemically more
stable.
• Microspheres received much attention not only for prolonged release, but also for targeting of anticancer drugs to
the tumor.
• There are two phases:
(a) Core material
(b) Coating material
• The product obtained by this process is called as micro particles, microcapsules, microsphere, coated granules,
and pellets. Particles having diameter between 3-800 µm are known as microparticles or microcapsules or
microspheres. Particles larger than 1000 µm are known as macroparticles.
Applications of microencapsulation:
1. Pharmaceuticals: In the pharmaceutical industry, microencapsulation is used to protect sensitive drugs from
degradation, improve their stability, and control their release. It allows for controlled drug delivery, which can
enhance drug efficacy, reduce side effects, and improve patient compliance.
2. Food and Beverages: Microencapsulation is widely used in the food industry to protect sensitive ingredients
(e.g., flavors, nutrients, vitamins, or oils) from exposure to oxygen, moisture, or light. It helps to prolong shelf life,
prevent ingredient interactions, and maintain product quality.
3. Personal Care Products: In cosmetics and personal care products, microencapsulation is employed to
encapsulate fragrances, essential oils, and active ingredients. This enables the controlled release of these substances
over time, providing longer-lasting effects and improving the product's overall performance.
4. Agrochemicals: In agriculture, microencapsulation is used for the controlled release of pesticides, herbicides,
and fertilizers. This results in reduced environmental impact, increased efficacy, and extended protection against
pests and diseases.
5. Textiles: Microencapsulation can be applied to textiles to impart various properties such as fragrance,
antimicrobial effects, or temperature regulation. For example, fabrics with microencapsulated fragrances can
provide long-lasting freshness.
6. Self-Healing Materials: Microencapsulation is used in the development of self-healing materials, where
microcapsules containing healing agents are embedded within the material. When the material is damaged, the
capsules rupture, releasing the healing agent, and repairing the damage.
7. Printing Industry: Microencapsulation is employed in carbonless copy paper, where microcapsules containing
color-forming chemicals are ruptured during writing or printing to create duplicate copies.
8. Cosmeceuticals: Cosmeceutical products, which combine cosmetic and pharmaceutical properties, often use
microencapsulation to deliver active ingredients effectively into the skin, providing various skincare benefits.
9. Fragrance and Air Fresheners: Microencapsulated fragrances are used in air fresheners and other products to
release scents gradually, extending their longevity.
10. Biotechnology: In the biotech industry, microencapsulation is utilized for controlled delivery of enzymes,
proteins, and other bioactive compounds.
• Overall, microencapsulation technology offers a wide range of benefits, including enhanced stability, controlled
release, protection from external factors, and improved performance of the encapsulated substances, making it a
valuable tool in multiple industries.
ADVANTAGES OF MICROENCAPSULATION
1. Reliable means to deliver the drug to the target site and to maintain the desired concentration at the site of
interest without untoward effects.
2. Solid biodegradable microspheres have the potential throughout the particle matrix for the controlled release of
drug.
3. Microspheres received much attention for targeting of anticancer drugs to the tumor. 4. Reduces the dosing
frequency and thereby improve the patient compliance.
5. They could be injected into the body due to the spherical shape and smaller size.
6. Better drug utilization will improve the bioavailability and reduce the incidence or intensity of adverse effects.
7. Microsphere morphology allows a controllable variability in degradation and drug release.
Coacervation
• Coacervation microencapsulation is the phase separation of one or many hydrocolloids from the initial solution
and the subsequent deposition of the newly formed coacervate phase around the active ingredient suspended or
emulsified in the same reaction media.
• Coacervation is a unique microencapsulation technology because of the very high payloads achievable up to 99%
and the controlled release possibilities based on mechanical stress, temperature or sustained release.
• Coacervation is typically used to encapsulate flavor oil and can also be adapted for the encapsulation of fish oils,
nutrients, vitamins, preservatives and enzymes.
• There are two methods for coacervation are available, namely simple and complex processes. The mechanism of
microcapsule formation for both processes is identical, except for the way in which the phase separation is carried
out.
1. Simple Coacervation
• A desolvation agent is added for phase separation. Whereas complex coacervation involves complexation
between two oppositely charged polymers.
• The general process consists of three steps under continuous agitation:
1. Formation of three immiscible chemical phases.
2. Deposition of coating.
3. Rigidization of coating.
Step 1:
• Three immiscible phases are as:
(a) Liquid manufacturing vehicle phase.
(b) Core material phase.
(c) Coating material phase.
• Coating material phase formed by utilizing following methods:
(a) Temperature change.
(b) By addition of incompatible polymer.
(c) By non-solvent addition.
(d) By salt addition.
(e) Polymer-polymer interaction.
Step 2:
• In step 2, the deposition of the liquid polymer around the interface formed between the core material and the
liquid vehicle phase. In many cases physical or chemical changes in the coating polymer solution can be induced so
that phase separation of the polymer will occur.
• Finally the prepared microcapsules are stabilized by crosslinking, desolvation or thermal treatment. Equipment
required for microencapsulation; this method is relatively simple; it consists mainly of jacketed tank with variable
speed agitator.
7. What are buccal DDS? Explain the formulation of buccal drug delivery system.
Buccal Drug Delivery Systems : Buccal drug delivery systems interact with the mucus layer covering the mucosal
epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption.
The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require
increased duration of stay in GIT. Thus, buccal dosage forms are advantageous in increasing the drug plasma
concentrations and also therapeutic activity.
Oral Epithelium: • The epithelium of the mouth consists of stratified, squamous epithelium, which can be
keratinized, or nonkeratinized. It contains following layers: Stratum distendum Stratum filamentosum Stratum
suprabasale, Stratum basale.
Lamina Propria: Constitutes of a continuous sheet of connective tissue containing collagen, elastic fibers and
cellular components in a hydrated ground substance. It also carries blood capillaries and nerve fibers that serve the
mucosa. It is through the blood vessels in the lamina propria that drug moieties can gain entry to the systemic
circulation.
• Submucosa: This is a layer of loose connective tissue that supports the epithelium and also contains blood
vessels, lymphatics and nerves.
Formulation
• Pharmaceutical considerations: Great care needs to be exercised while developing a safe and effective buccal
adhesive drug delivery device. Factors influencing drug release and penetration through buccal mucosa are
organoleptic factors and effects of additives used to improve drug release pattern and absorption, the effects of
local drug irritation caused at the site of application are to be considered while designing a formulation.
1. Physiological Considerations
• Physiological considerations such as; texture of buccal mucosa, thickness of the mucus layer, its turn over time,
effect of saliva and other environmental factors are to be considered in designing the dosage forms.
• For e.g. Saliva contains moderate levels of esterases, carbohydrases, and phosphatases that may degrade certain
drugs. Although saliva secretion facilitates the dissolution of drug, involuntary swallowing of saliva also affects its
bioavailability
2. Pharmacological Considerations
• Drug absorption depends on the partition coefficient of the drugs. Generally, lipophilic drugs absorb through the
transcellular route, whereas; hydrophilic drugs absorb through the paracellular route. Chemical modification may
increase drug penetration through buccal mucosa. Residence time and local concentration of the drug in the
mucosa, the amount of drug transported across the mucosa into the blood are the responsible factors for local or
systemic drug delivery. Optimization by a suitable formulation design fastens drug release from the dosage form
and taken up by the oral mucosa.
• Basic Components for BDDS
• Buccal adhesive drug delivery systems with the size 1-3 sq.cm and a daily dose of 25 mg or less are preferable.
The maximal duration of buccal delivery is approximately 4-6 hrs. To make such dosage form following
components are required:
1. Bioadhesive Polymers
• Bioadhesive formulations use polymers as the adhesive component. These formulations are often water soluble
and when in a dry form attract water from the biological surface and this water transfer leads to a strong interaction.
It also forms viscous liquids when hydrated with water that increases their retention time over mucosal surfaces and
may lead to adhesive interactions. They should possess certain physicochemical features including hydrophilicity,
numerous hydrogen bond-forming groups, and flexibility for interpenetration with mucus and epithelial tissue, and
visco-elastic properties.
2. Polymers in Buccal Drug Delivery
• Polymers remain the most versatile class of biomaterials, being extensively applied in medicine and
biotechnology as well as in the food and cosmetic industries. Applications include surgical devices, implants and
supporting materials (for e.g. artificial organs, prostheses and sutures), drug-delivery systems with different routes
of administration and design, carriers of immobilized enzymes and cells, biosensors, components of diagnostic
assays, bioadhesives, ocular devices, and materials for orthopedic applications.
• Classifying the properties of polymers for their selection as biomaterials is challenging, because a wide variety of
materials are available for a particular application (e.g. surgery, drug delivery) and no single, simple set of methods
can be used to characterize polymers.
Characteristics of an Ideal Polymer for Mucoadhesive Drug Delivery System
• The polymer and its degradation products should be non-toxic and non-absorbable from the GI tract.
• It should be non-irritant to the mucous membrane.
• It should preferably form a strong non-covalent bond with mucin-epithelial cell surfaces.
• It should preferably adhere quickly to moist tissue and should possess some site specificity.
• It should allow easy incorporation of the drug and offer no hindrance to its release. The polymer must not
decompose on or during the shelf life of the dosage form.
• The cost of the polymer should not be high so that the prepared dosage form remains competitive.
 8. What is an implant? Explain the formulation of implants with a suitable example.
Implant : An implant refers to a small device or formulation that is designed to be placed inside the body to deliver
therapeutic substances, such as drugs or hormones, over an extended period of time. The implant serves as a
reservoir or depot for the drug, gradually releasing it into the surrounding tissues or bloodstream at a controlled
rate.
• The concept behind an implant in a novel drug delivery system is to provide a sustained and controlled release of
medication, eliminating the need for frequent dosing or injections. This offers several advantages over conventional
drug delivery methods, such as oral tablets or injections, which often result in fluctuating drug levels in the body.
• Implants can be made from a variety of materials, including biocompatible polymers, metals, or even biological
tissues. These materials are carefully selected based on their compatibility with the body, stability of the drug
within the implant, and ability to release the drug in a controlled manner.
• The drug is typically loaded into the implant either as a solid or in a dissolved or dispersed form within a polymer
matrix. The choice of drug formulation depends on factors such as drug stability, solubility, and desired release
kinetics. The implant may also contain additional components, such as permeation enhancers or rate-controlling
membranes, to further modulate the drug release profile.
• Once the implant is placed in the body, the drug is released through various mechanisms. These mechanisms can
include diffusion of the drug through the implant matrix, erosion or degradation of the implant material, or a
combination of both. The release rate can be tailored by adjusting the properties of the implant, such as the polymer
composition, drug loading, or implant size and shape.
• The benefits of implantable drug delivery systems include improved patient compliance, reduced side effects, and
enhanced therapeutic efficacy. By maintaining a consistent drug concentration within the desired target area,
implants can provide a more sustained and prolonged therapeutic effect compared to traditional dosing regimens.
Additionally, implants can be designed to be easily removable or replaceable, allowing for flexibility in treatment.
• Implantable drug delivery systems have found applications in various medical fields, including contraception,
hormone replacement therapy, pain management, and treatment of chronic conditions such as diabetes or cancer.
Ongoing research and development in this area continue to advance the design and functionality of implantable
devices, leading to improved patient outcomes and quality of life.
• Implantable drug delivery systems are designed to deliver drugs directly to the target site within the body over an
extended period of time. These systems typically consist of an implantable device that contains the drug
formulation and a mechanism for controlled release.
Formulations used in implantable drug delivery systems :
1. Solid Implants: Solid implants are composed of a drug-incorporated polymer matrix. The drug is dispersed or
dissolved within the polymer, which provides controlled release as it degrades or erodes over time. Examples of
solid implant formulations include drug-loaded rods, pellets, or microparticles.
2. Microcapsules: Microcapsules are small, spherical particles that encapsulate the drug within a biocompatible
polymer shell. The drug can be either dissolved or dispersed within the core of the microcapsule. The polymer shell
controls the release of the drug over time. Microcapsules can be implanted directly or incorporated into other
implantable devices.
3. Hydrogels: Hydrogels are three-dimensional networks of hydrophilic polymers that can absorb and retain large
amounts of water or biological fluids. They can be loaded with drugs and implanted at the target site. The drug
release from hydrogels is generally controlled by diffusion through the hydrogel matrix or by the degradation of the
hydrogel itself.
4. Lipid-Based Formulations: Lipid-based formulations utilize liposomes or lipid nanoparticles to encapsulate the
drug. Liposomes are vesicles composed of lipid bilayers that can entrap hydrophilic or hydrophobic drugs within
their aqueous or lipid cores. Lipid nanoparticles, such as solid lipid nanoparticles (SLNs) or nanostructured lipid
carriers (NLCs), consist of drug-loaded lipid matrices. These lipid-based formulations can provide sustained drug
release upon implantation.
5. Biodegradable Polymers: Biodegradable polymers are commonly used in implantable drug delivery systems.
These polymers degrade over time, releasing the drug payload. Examples of biodegradable polymers include
poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), and poly(caprolactone) (PCL). The drug can be
incorporated within the polymer matrix or encapsulated in microspheres or nanoparticles made from these
polymers.
• It's important to note that the specific formulation used in an implantable drug delivery system depends on factors
such as the drug's physicochemical properties, desired release profile, target site, and the duration of therapy
required. Researchers and pharmaceutical companies may employ different formulation strategies to optimize drug
release kinetics and therapeutic efficacy for a given application.
Ideal Properties of an Implantable Drug Delivery System
1. Environmentally stable. 2. Biocompatible. 3. Easy to sterilize. 4. Rate controlled release of drug.
5. Improve patient compliance by reducing the frequency of the drug administration over the entire period of
treatment.
6. Easy to manufacture and relatively inexpensive. 7. Good mechanical strength. 8. Free from surgical procedure.
9. What is transdermal DDS? Explain the different formulation approaches for transdermal DDS.
10.Explain factors affecting transdermal permeation of drugs.
Factors Affecting Transdermal Drug Delivery System
A. Physicochemical Properties of Drug
Following are the Physiochemical Properties of the Drug:
1. Partition coefficient
2. Molecular size
3. Solubility/Melting point
4. Ionization
5. Diffusion Coefficient
1. Partition Coefficient : Drug possess both water and lipid solubility. Ideal partition coefficient for intermediate -
ansdermal delivery is log K1-3. For highly lipophilic drug (log k < 3), intracellular route is avourable, whereas for
hydrophilic drugs (log k < 1), it is permeated via transcellular route.
2. Molecular Size : Molecular size of the drug is inversely proportional to transdermal flux. The ideal molecular
size of drug molecule for transdermal delivery is <400.
3. Solubility/Melting Point : Most organic solutes have high melting point and low solubility at normal
temperature nd pressure. Lipophilic drug permeates faster than hydrophilic substances, but it should also ave
aqueous solubility as needed in most of topical formulations.
4. Ionization : Unionized drug permeates the skin as according to pH-Partition hypothesis.
5. Diffusion Coefficient : Penetration of drug depends on diffusion coefficient of drug. At a constant temperature,
the diffusion coefficient of drug mainly depends on properties of drug, diffusion medium and their interaction.
B. Physicochemical Properties of Drug Delivery System
Following are the Physicochemical Properties of Drug Delivery System:
1. Release characteristics.
2. Composition of drug delivery system.
3. Enhancement of Transdermal permeation.
1. Release Characteristics : Drug release mechanism mainly depends on drug molecules which are dissolved or
suspended in the delivery system and on interfacial partition coefficient or pH of the drug from delivery system to
the skin tissue. If the drug is easily released from the delivery system, the rate of transdermal permeation will be
higher.
2. Composition of Drug Delivery System : Composition may not affect release properties but may affect its
permeability functionality. For example, methyl salicylate is more lipophilic than parent acid, i.e. salicylic acid, and
its percutaneous absorption is high when applied to skin in a lipoidal vehicle. 3023
3. Enhancement of Transdermal Permeation : Majority of drugs will not permeate into skin for therapeutic use.
Some enhancers are used for synergistic action without showing its properties (e.g. dimethyl sulphoxide, acetone,
propylene glycol and tetradihydrofuryl alcohol).
C. Physiological Properties
Following are the Physiological and Pathological Conditions of Skin:
1. Skin permeation barrier in neonate and infants
2. Skin barrier properties in aged skin
3. Race
4. Skin temperature
1. Skin Barrier Properties in the Neonate and Young Infant : The skin surface of the newborn is slightly
hydrophobic, relatively dry and rough when compared to that of older infants. Stratum corneum hydration
stabilizes by the age of 3 months.
2. Skin Barrier Properties in Aged Skin : There are some changes in the physiology of aged skin (465 years).
The moisture content of human skin decreases with age. There is a destruction of the epidermal junction and
Consequently, the area available for transmission into the dermis is diminished.
3. Race : Racial differences between black and white skins have shown some anatomical and physiological
functions of the skin. In black skin, there is increased intracellular permeation due to higher lipid content and
higher electrical skin resistance levels when compared to whites, but this difference is not detected in stripped skin.
4. Skin Temperature : The human body maintains a temperature of 32°C-37°C across the skin. Hence, increase in
temperature leads to increase in diffusion through the tissue.
Advantages of Transdermal Drug Delivery System
1. Suitable for drug candidates with short half-life and low therapeutic index.
2. No first pass effect.
3. Reduction in dosing frequency.
4. Minimization of daily intake of drug.
5. Reduction of fluctuations in plasma drug concentration.
6. Improves patient compliance.
7. Minimization of side effects.
8. Simple and non-invasive.
9. Alternate route for patients who are unable to take oral medications.
10. Dose delivery unaffected by vomiting or diarrohoea.
11. Drug administration stops with patch removal.
Disadvantages of Transdermal Drug Delivery System
1. The transdermal route of administration is unsuitable for drugs that irritate or sensitize the skin.
2. Only relatively potent drugs are suitable for transdermal delivery due to the natural limits of drug entry by the
skin's impermeability.
3. Technical difficulties with the adhesion of the systems to different skin types and under various environmental
conditions.
4. A constant concentration gradient is difficult to maintain.
Basic Components of TDDS
• Polymer matrix/drug reservoir.
• Membrane
• Drug
• Permeation enhancers
• Pressure-sensitive adhesives (PSA)
• Backing laminates
• Release liner
• Other excipients like plasticizers and solvents
11.Give an account on formulation of nasopulmonary drug delivery system.
The Components of the Nasal Formulations:
• Drug Terbutaline sulphate. -
• Viscosifying Agents - Hydroxypropyl cellulose
• Solubilizers - Glycol, Alcohol, Cyclodextrins.
• Surfactants SLS, Polyacrylic acid.
• Bio-adhesive Polymers - Methylcellulose, Carboxymethylcellulose
• Preservatives - Parabens, Benzalkonium chloride.
• Antioxidants - Sodium metabisulphite.
Nasal Formulations :
1. Nasal Gels: These are highly viscous, thickened solutions or suspensions. Theses have
following advantages:
• Reduction of post nasal drip due to high viscosity.
• Reduction of taste impact due to reduced swallowing.
• Reduction of anterior leakage of the formulation.
These are useful as there is reduction of irritation by using emollient excipients.
2. Nasal Drops: These are one of the simple and convenient systems developed for nasal delivery. The main
disadvantage of this system is the lack of the dose precision and therefore nasal drops may not be suitable for
prescription products. It has been reported that nasal drops deposit Human Serum albumin in the nostrils more
efficiently than nasal sprays.
3. Nasal Ointments: These are translucent, homogenous, viscous, semi-solid preparations intended to be instilled
in the nose. Due to their viscosity they will not ooze out of the nose.
4. Nasal Sprays: Solution and Suspension formulations can be formulated into nasal sprays, Due to the availability
of metered dose pumps and actuators, a nasal spray can deliver an exact dose from 25-200 µm. The particle size
and morphology (for suspensions) of the drug and viscosity of the formulation determine the choice of pump and
actuator assembly.
5. Nasal Powder: This dosage form may be developed if solution and suspension dosage forms cannot be
developed. For e.g. due to lack of drug stability.
The advantages of the nasal powder dosage form are the absence of preservative and superior stability
of the formulation. However, the suitability of powder formulation is dependent on the solubility, particle size,
aerodynamic properties and nasal irritancy of the active drug and/or excipients. Local application of drug is another
advantage of this system.
6. Liposomes: Liposomal nasal solutions can be formulated as drug alone or in combination with pharmaceutically
acceptable excipients. They are administered to the respiratory tract as an aerosol or solution for a nebulizer, or as a
microfine powder for insufflations, above or in combination with an inert carrier such as; lactose, the particles of
the formulation have diameters of less than 50 microns.
7. Microspheres: The main usefulness of specialized system in designed nasal products is that, it prolongs the
contact with the nasal mucosa. The microspheres in their powder form swell in contact with nasal mucosa to form a
gel and controls the rate of clearance from the nasal cavity. Thus, increases the absorption and bioavailability by
adhering to the nasal mucosa and increases the nasal residence time of drug. The ideal microsphere particle size
requirement for nasal delivery should range from 10-50 μm as smaller particles.
Applications Of Nasal Drug Delivery System :
1. Delivery of non-peptide pharmaceuticals. For e.g. Adrenal corticosteroids, Hormones like Progesterone,
Vitamin, Cardiovascular drugs, etc.
2. Delivery of peptide-based pharmaceuticals. For e.g. Insulin, Calcitonon, Pituitary hormones.
3. Delivery of diagnostic agents. For e.g. Phenolsulfonphthalein is used to diagnose kidney function.
4. Delivery of vaccines through nasal route. For e.g. Anthrax and Influenza are treated by using the nasal vaccines.
5. Delivery of drugs to brain through nasal cavity. For e.g. Parkinson's disease, Alzheimer's disease.
Advantages Of Nasal Drug Delivery System
1. Drug degradation that is observed in the gastrointestinal tract is absent.
2. Hepatic first pass metabolism is avoided.
3. Rapid drug absorption and quick onset of action can be achieved.
4. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other
approach.
5. The nasal bioavailability for smaller drug molecules is good.
6. Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery.
7. Studies so far carried out indicate that the nasal route is an alternate to parenteral route, especially, for protein
and peptide drugs.
8. Convenient for the patients, especially for those on long term therapy, when compared with parenteral
medication.
9. Drugs possessing poor stability in G.I.T. fluids are given by nasal route.
10. Polar compounds exhibiting poor oral absorption may be particularly suited for this route of delivery.
Disadvantages of Nasal Drug Delivery System
1. The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly
established.
2. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal
irritation.
3. Nasal cavity provides smaller absorption surface area when compared to GIT.
4. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the
substance and from constituents added to the dosage form.
5. Certain surfactants used as chemical enhancers may disrupt and even dissolve membrane in high concentration.
6. There could be a mechanical loss of the dosage form into the other parts of the respiratory tract like lungs
because of the improper technique of administration.
The different approaches:
1. Prodrug Approach: The absorption of peptides like angiotensin II, Bradykinin, Vasopressin and Calcitonin are
improved when prepared into enamine derivatives.
2. Structural Modification: Chemical modification of Salmon Calcitonin to ecatonin (C-N bond replaces the S-S
bond) showed better bioavailability.
3. Particulate drug Delivery:
(i) Microspheres, Nanoparticles and Liposomes.
(ii) Nasal Enzyme Inhibitors.
• Peptides and Proteases.
• Triptin Aprotinin, Borovaline, Amastatin, Betaststin and Boroleucin inhibitors.
12. Define ocular drug delivery system. Explain different types of ocular DDS.
Ocular Drug Delivery System : The eye is a complex organ with an unique anatomy and physiology. The
structure of eye Can be divided into two main parts: anterior segment and posterior segment. Anterior segment of
the eye occupies approximately one-third while the remaining portion is occupied by the posterior segment. Tissues
such as cornea, conjunctiva, aqueous humor, iris, ciliary body and lens make up the anterior portion. Back of the
eye or posterior segment of the eye include; sclera, choroid, retinal pigment epithelium, neural retina, optic nerve
and vitreous humor. The anterior and posterior segment of eye is affected by various vision threatening diseases.
Diseases affecting anterior segment include, but not limited to glaucoma, allergic conjunctivitis, anterior uveitis
and cataract. The age-related macular degeneration (AMD) and diabetic retinopathy are the most prevalent diseases
affecting posterior segment of the eye.
Ocular administration of drug is primarily associated with the need to treat Ophthalmic diseases. The eye is the site
for topical administration of a medication. The main objective for the ophthalmic drug delivery is that, it should
sustain the drug release and to remain in the vicinity of front of the eye for prolonged period of time.
There are specialized dosage forms designed to be instilled onto the external surface of the eye (topical),
administered inside (intraocular) or adjacent (periocular) to the eye or used in conjunction with an ophthalmic
device.
The novel approach of drug delivery in which the drug is instilled on the cul de sac cavity of the eye (space
between eye lids and eye balls) is known as Ocular Drug Delivery System.
The most commonly used employed dosage forms are the Solutions, Suspensions and Ointments. The newest
dosage forms are the Gels, Gel forming Solutions, Ocular inserts, intravitreal injections and implants.
Methods To Overcome Barriers To Ocular Drug Delivery : Drug delivery through topical or systemic route
faces a number of challenges limiting their success. Advancements in drug design, drug formulation and devices
have led to successful products. But the scientists have experimented with alternate routes of drug delivery that can
overcome barriers presented by the more conventional routes. Injections through visible portions of the sclera
targeting various sections of ocular structures are routinely carried out by a trained specialist.
1. Intravitreal Injections : Intravitreal injection (IVI) involves delivering of the drug formulation directly into the
vitreous humor through pars plana. This method provides direct access to the vitreous and avoids both the cornea
and also the scleral blood vessels. Formulations such as; solution, suspension or a depot formulation can be
administered through this route. Drug elimination occurs either through the retina or the anterior chamber through
the aqueous humor following a first order rate of decline. This rate of elimination has a linear correlation with the
molecular weight of the drug. Larger molecules tend to have longer half-lives as high as several weeks as compared
to less than 3 days for low molecular weight compounds. IVI administration is associated with adverse effects such
as; retinal detachment, cataract, hyperemia and endophthalmitis. Sustained release drug delivery systems can help
by lowering frequency of administration and thus allow for better patient compliance.
2. Subconjunctival Injections : This injection delivers the drug beneath the conjunctival membrane that lines the
inner surface of eyelid. It allows for circumvention of both cornea and conjunctiva allowing the drug direct access
to the sclera. It is much less invasive with lesser side effects when compared to intravitreal injections. The method
is an excellent route for delivering hydrophilic drugs as it bypasses their rate-limiting barriers allowing more drugs
to enter into vitreous. It is an excellent route for delivering both depot forming formulations as well as for the
delivery of macromolecular drugs such as Avastin (bevacizumab: a recombinant monoclonal antibody against
VEGF) and insulin.
3. Retrobulbar and Peribulbar Route : Retrobulbar injection is given through eyelid and orbital fascia and it
places the drug into retrobulbar space. This mode administers the drug to the back of the eye ball and is used to
deliver drugs such as; antibiotics and corticosteroids. This route is especially applicable for the delivery of
anesthetic agents as it causes minor or no change in IOP though in certain orbital diseases the reverse is also
possible. Yet, it is a very delicate procedure as it may damage the optic nerve and thus requires proper expertise
and equipment. Peribulbar route for drug delivery involves injections above and/or below the globe. It is also a
viable route for the delivery of anesthesia especially in cases of cataract surgery. It is a safer route compared to the
retrobulbar route with reduced risk of injury. Though it is a safer method, unlike retrobulbar injection multiple
cases of elevated intraocular pressure after peribulbar injections have been reported.
4. Sub-Tenon Injections : Sub-tenon injections are administered into a cavity between tenon's capsule and sclera
using a blunt cannula. Pre-operative deep sedation is also not a requirement for this procedure. Sub-tenon route
appears to be a better and safer route for delivering anesthesia relative to retrobulbar and peribulbar administration
since it does not require sharp needles. Steroids injected through this route have also been shown to be effective in
the treatment of uveitis, cystoid macular edema, complicating uveitis and non-necrotizing scleritis.
5. Intracameral Injections : Intracameral route is similar to intravitreal injections, but this injection delivers drug
to the anterior chamber. Drugs administered through this route are limited to anterior chamber with very limited
access to the posterior segment. It is generally employed for anterior segment procedures such as cataract surgery.
Clinical studies have reported that intracamerally delivered dexamethasone is effective in reducing post-operative
inflammation in glaucomatous and non-glaucomatous patients. It is an efficient and often a more cost- effective
method of delivering antibiotics relative to topical antibiotics and antifungal agents.
13.Give an account on intra ocular barriers.
Barriers To Ocular Drug Delivery : The reason why it is difficult to achieve relevant therapeutic doses within the
eye is primarily due to the presence of multiple barriers. When a dosage form is either administered topically or
systemically, it faces multiple obstacles before it reaches its site of action. As a result, ocular bioavailability from
topically administered drug is usually only 1%-7% of the applied dose. These barriers can be broadly classified as
anatomical barriers and physiological barriers.
1. Anatomical Barriers : When a dosage form is topically administered, there two routes of entry: either through
the cornea or via the non-corneal route.
(a) The cornea is a very tight multilayered tissue that is mainly composed of five sections:
(i) Epithelium-Principle barrier (Hydrophilic drug transport through intercellular spaces).
(ii) Bowman's membrane.
(iii) Stroma-multiple layers of collagen fibers containing pores and channels (for lipophilic drug, significant
barrier).
(iv) Descemet's membrane.
(v) Endothelium.
Prevention: Optimum bioavailability, right balance of lipophilic and hydrophilicity.
(b) Non-corneal route bypass the cornea and involves movement across conjunctiva and sclera.
(c) Conjunctiva: It is more permeable than cornea for hydrophilic molecules.
2. Physiological Barrier : The eye's primary line of defense is its tear film. Bioavailability of RAICE drugs is
further reduced by precorneal factors such as; solution drainage, tear dilution, tear turnover, and increased
lacrimation. This in turn lowers the exact time for absorption leading to reduced bioavailability.
Prevention: So, the drugs administered as eye drops need to be isotonic and non- irritating to prevent significant
precorneal loss.
3. Blood Ocular Barrier : This barrier normally keeps most drugs out of the eye, but inflammation breaks down
this barrier allowing drugs and large molecules to penetrate into the eye.
(a) Blood aqueous barrier: The ciliary epithelium and capillaries of the iris.
(b) Blood retinal barrier: Non-fenestrated capillaries of the retinal circulation and tight junctions between retinal
epithelial cells preventing passage of large molecules from chorio-capillaris into retina.
4. Drug and Dosage Form Related Factors:
(a) Solubility: Solubility is dependent on the pK, of the drug and pH of the solution.
(b) Lipophilicity: Lipophilicity and corneal permeability display sigmoidal relationship. This is because of the
differential permeability of the different layers of cornea towards lipophilic drugs. Lipophilic drugs tend to
permeate easily through the epithelial layers of cornea and the hydrophilicity of the inner layer of comea (stroma)
requires hydrophilicity for optimal permeation.
(c) Molecular weight and size: The weight and size of molecules play a critical role in deciding its overall
permeability through paracellular route. Molecules having molecular weight less than 500 Dalton are able to
permeate readily.
(i) The conjunctiva has larger paracellular pore diameter thus allowing permeation of larger molecules such as
small and medium size peptides (5000-10000 Daltons).
(ii) Permeation across sclera occurs through the aqueous pores and molecular size of the solute can be the
determining factor. Sucrose (molecular weight - 342 Daltons) permeates 16 times faster than inulin (molecular
weight - 5000 Daltons). Scleral permeability is approximately half of conjunctiva but much higher than cornea.
Advantages of Ocular Drug Delivery System
1. It can be easily administered.
2. They have quick absorption and effect.
3. Less visual and systemic side effects.
4. Better patient compliance.
Disadvantages of Ocular Drug Delivery System :
1. Residence time of drug at eye surface is less.
2. Poor bioavailability.
3. The instability of the dissolved drug.
4. The low concentration of preservative reduces shelf life after opening the bottle.
Ideal Characteristics of Ocular Drug Delivery System :
1. It should be sterile.
2. It should be isotonic to body fluids.
3. Buffer/pH adjustment.
4. Less drainage tendency.
5. Minimum protein binding.
14.Explain formulation approaches for GRDDS.
Approaches for GRDDS
1. Floating drug delivery systems.
2. Mucoadhesive systems.
3. Swellable systems.
4. High density systems.
1. Floating Drug Delivery System : Floating drug delivery systems (FDDS) have a bulk density lower than gastric
fluids and thus remain buoyant in stomach for a prolonged period of time, without affecting the gastric emptying
rate. While the system floats on gastric contents, the drug is released slowly at a desired rate from the system. After
the release of drug, the residual system is emptied from the stomach. This results in an increase in gastric retention
time and a better control of fluctuations in plasma drug concentrations. Floating systems can be classified into two
distinct categories, (i) Non-effervescent and (ii) Effervescent systems.
A. Effervescent:
(a) Gas generating systems.
(b) Volatile liquid containing systems.
(c) Inflatable gastrointestinal delivery systems.
(d) Intragastric osmotically controlled drug delivery system.
B. Non-Effervescent:
(a) Colloidal gel barrier systems.
(b) Alginate beads.
(c) Hollow microspheres.
(d) Microporous compartment system.
A. Effervescent
(a) Gas Generating Systems : Intra Gastric Single Layer Floating Tablets or Hydrodynamically Balanced
System (HBS) : These are as shown in Fig. 3.16 and formulated by intimately mixing the CO2 generating and the
drug within the matrix. These have a bulk density lower than gastric fluids and therefore remain floating in the
stomach unflattering the gastric emptying rate for a prolonged period. The drug is slowly released at a desired rate
from the floating system and after the complete release, the residual system is expelled from the stomach. This
leads to an increase in the gastric retention time and a better control over fluctuations in plasma drug concentration.
Intra Gastric Bilayer Floating Tablets : These are also compressed tablets and containing two layers i.e.
(i) Immediate release layer
(ii) Sustained release layer
(b) Volatile Liquid/Vacuum Containing Systems: Intragastric Floating Gastrointestinal Drug Delivery
System: These systems can be made to float in the stomach because of floatation chamber, which may be a vacuum
or filled with air or a harmless gas, while drug reservoir is encapsulated inside a microporous compartment.
(c) Inflatable Gastrointestinal Delivery Systems : In these systems, an inflatable chamber is incorporated, which
contains liquid ether that evaporates at body temperature to cause the chamber to inflate in the stomach. These
systems are fabricated by loading the inflatable chamber with a drug reservoir, which can be a drug, impregnated
polymeric matrix, then encapsulated in a gelatin capsule. After oral administration, the capsule dissolves to release
the drug reservoir together with the inflatable chamber. The inflatable chamber automatically inflates and retains
the drug reservoir compartment in the stomach. The drug continuously released from the reservoir into the gastric
fluid.
(d) Intragastric Osmotically Controlled Drug Delivery System: It is comprised of an osmotic pressure-
controlled drug delivery device and an inflatable floating support in a biodegradable capsule. In the stomach, the
capsule quickly disintegrates to release the intragastric osmotically controlled drug delivery device. The inflatable
support inside forms a deformable hollow polymeric bag that contains a liquid that vaporizes at body temperature
to inflate the bag. The osmotic pressure-controlled drug delivery device consists of two components drug reservoir
compartment and an osmotically active compartment. The drug reservoir compartment is enclosed by a pressure
responsive collapsible bag, which is impermeable to vapour and liquid and has a drug delivery orifice. The
osmotically active compartment contains an osmotically active salt and is enclosed within a semi-permeable
housing. In the stomach, the water in the gastro-intestinal fluid is continuously absorbed through the semi-
permeable membrane into osmotically active compartment to dissolve the osmotically active salt. An osmotic
pressure is thus created which acts on the collapsible bag which forces the drug reservoir compartment to reduce its
volume and which in turn activate the drug release from the drug solution compartment through delivery orifice.
The floating support is also made to contain a bio-erodible plug that erodes after a predetermined time to deflate the
support. The deflated drug delivery system is then emptied from the stomach.
B. Non-Effervescent
(a) Colloidal Gel Barrier Systems : • Such systems contain drug with gel forming hydrocolloids meant to remain
buoyant on stomach contents.
• These systems incorporate a high level of one or more gel forming highly s wellable cellulose type hydrocolloids.
For e.g. HPMC, NaCMC.
• On coming in contact with gastric fluids forms a viscous core.
• Incorporates H2O and entraps air.
• Density of system falls below 1 gm/cm³. Then it starts floating.
(b) Microporous Membrane System: Based on the encapsulation of drug reservoir inside a Microporous
compartment,
• The peripheral walls of the drug reservoir compartment are completely sealed to prevent any direct contact of the
gastric mucosal surface with the undissolved drug.
• In stomach, the floatation chamber containing entrapped air causes the delivery system to float over the gastric
contents.
• Gastric fluid enters through the apertures, dissolves the drug and carries the dissolved drug for absorption.
(c) Alginate Beads: • Spherical beads of approximately 2.5 mm in diameter can be prepared by dropping a sodium
alginate solution into aqueous solutions calcium chloride, causing precipitation of calcium alginate.
• Sodium alginate + Calcium chloride, Calcium alginate + NaCl.
• The beads are then separated and frozen in liquid nitrogen, and freeze dried at -40°C for 24 hours, leading to the
formation of porous system.
• Maintain a floating force of over 12 hours.
(d) Hollow Microspheres : • Microballoons / hollow microspheres loaded with drugs are prepared by simple
solvent evaporation method.
• Commonly used polymers to develop these systems are polycarbonate, cellulose acetate, calcium alginate,
Eudragit S, agar and pectin, etc.
• These systems have capacity to float on acidic dissolution media containing surfactant for about 12 hours invitro.
2. Bioadhesive or Mucoadhesive Drug Delivery Systems : • Bioadhesive drug delivery systems are used as a
delivery device within the human to enhance drug absorption in a site-specific manner. In this approach, bio-
adhesive polymers are used and they can adhere to the epithelial surface in the stomach.
• Thus, they improve the prolongation of gastric retention. The basis of adhesion is that, a dosage form can stick to
the mucosal surface by different mechanisms. These mechanisms are:
1. The wetting theory, which is based on the ability of bioadhesive polymers to spread and develop intimate contact
with the mucous layers.
2. The diffusion theory, which proposes physical entanglement of mucin strands the flexible polymer chains, or an
interpenetration of mucin strands into the porous structure of the polymer substrate.
3. The absorption theory, suggests that bio-adhesion is due to secondary forces such as; vander Waal forces and
hydrogen bonding.
4. The electron theory, which proposes attractive electrostatic forces between the glycoprotein mucin network and
the bio-adhesive material.
• Materials commonly used for bioadhesion are poly acrylic acid, chitosan, cholestyramine, sodium alginate,
hydroxypropyl methylcellulose (HPMC), sucralfate, tragacanth, dextrin, polyethylene glycol (PEG) and polylactic
acids, etc. Even though some of these polymers are effective at producing bioadhesive, it is very difficult to
maintain it effectively because of the rapid turnover of mucus in the gastrointestinal tract (GIT).
3. Expandable, Unfoldable and Swellable Systems : A dosage form in the stomach will withstand gastric transit
if it is bigger than pyloric sphincter. However, the dosage form must be small enough to be swallowed, and must
not cause gastric obstruction either singly or by accumulation. Thus, their configurations are required to develop an
expandable system to prolong gastric retention time (GRT):
1. A small configuration for oral intake.
2. An expanded gastro-retentive form.
3. A final small form enabling evacuation following drug release from the device.
• Thus, gastro-retentivity is improved by the combination of substantial dimension with high rigidity of dosage
form to withstand peristalsis and mechanical contractility of the stomach. Unfoldable and swellable systems have
been investigated and recently tried to develop an effective gastro-retentive drug delivery.
15.What is mean by polymer? Give its classification and discuss various properties of polymers.
Polymers : Polymers are compounds with high molecular masses formed by monomers. In Greek, the word poly
means 'many' and meros means 'units or parts'. Polymers play a major role in the development of drug delivery
technology by release of two types of drugs like; hydrophilic and hydrophobic in a synchronized manner and
constant release of formulations over extended periods.
Polymer Classification
The polymers are classified in to various types based on different categories. They are:
Classification of polymer
A. Based on origin of Source
1. Natural polymers
2. Semi-synthetic polymer
3. Synthetic polymers
B. Based on structure
1. Linear polymers
2. Branched chain polymers
3. Cross-linked
C. Based on molecular forces
1. Elastomers
2. Fibers
3. Thermoplastics
4. Thermosetting polymers
D. Based on mode of polymerization
1. Addition polymers
2. Condensation polymers
A.Classification Based on Source
1. Natural polymers: These are derived from natural sources and can be polysaccharides and protein in chemical
nature. For example: Albumin, Cellulose, Starch, Rubber, Wool.
2. Semi-synthetic polymers: These types of polymers are derived from naturally occurring polymers by means of
chemical modifications. For e.g. Vulcanized rubber, Gun cotton, Cellulose diacetate, HPMC, etc.
(i) Vulcanized rubber is used in making tyres as the process of vulcanization increases the mechanical strength of
natural rubber.
(ii) Gun cotton which is a cellulose nitrate is used in making explosives. Cellulose on acetylation with acetic
anhydride in the presence sulfuric acid forms cellulose diacetate which is used in production of treads and materials
like films, glasses, etc.
3. Synthetic polymers: Synthetic polymers are of artificial origin which consist of fibers. This is the polymer,
which was prepared by Laboratory is known as Synthetic Polymer. For example: Buna-S, Buna-R, Nylon,
Polythene, Polyester.
B. Classification Based on Structure
1. Linear polymers: The smallest repeating unit arranged in straight line path is known as Linear polymer. For
example: PVC.
2. Branched chain polymers: Contain linear chains having some branches. For example: low density polymer,
Polyethylene, HPLD polyethylene.
3. Cross linked chain polymers: In this type, all molecules are chemically bonded together, forming a three-
dimensional network. The bonding is usually covalent but other types such as; ionic bond is also possible. Cross-
linked polymers are produced from linear and branched polymers or directly from chemical precursor. For e.g.
Natural rubber, polyacrylamide gels, epoxies, alkyd resins, etc.
C. Classification Based on Polymerization
1. Additional polymers: Additional polymers are formed by the repeated addition of monomer possessing double
or triple bonds.
n(CH2 CH2) (CH2 CH2)-
• Ethylene polyethylene, one form of polymer is converted into another form of polymer by loss of atoms and ions
from molecule.
2. Condensation polymers : Condensation polymers formed by repeated condensation reaction between two
different bi-functional or tri- functional monomeric units. For e.g. terylene (dacron), nylon 6, 6, One polymer can
be converted into anther form of polymer without loss of atoms and ions from molecule.
D. Classification Based on Molecular Force
1. Nylon : Nylon is used as general name for all synthetic fiber forming polyamides, having a protein like structure.
These are the condensation polymers of diamine and dibasic acids. A number is usually suffixed with the Nylon
which refers to the number of carbon atoms present in the diamine and the dibasic acids respectively.
• For example: Nylon 6, 6. Nylon-6, 6 is obtained by the polymerization of adipic acid with hex methylene
diamine.
2. Thermoplastic polymers : These are linear or slightly branched long chain polymers, which can be softened on
heating and reversibly hardened on cooling repeatedly. Their hardness is a temporary property and varies with
temperature.
• The polymer under heating can convert from one state to another state and after cooling, it can again convert to its
original state.
For example: polyvinyl chloride.
Characteristics of Ideal Polymer
1. Low density.
2. Low coefficient of friction. 3. Good corrosion resistance.
4. Good mould ability.
5. Excellent surface finish can be obtained.
6. Can be produced with close dimensional tolerances.
7. Economical.
8. Poor tensile strength.
9. Low mechanical properties.
10. Poor temperature resistance.
11. Can be produced transparent or in different colours.