Prof.Dr. Md.
Harun Ar
Rashid
Head
Department of
Pharmacy
Tablets
■ Tablets are solid single unit
pharmaceutical dosage form
containing one or more active
ingredients with or without auxiliary
substances and prepared either by
molding or by compression.
■ -
■ Reference Books.
1.The theory and practice of Industrial
Pharmacy By Leon Lachman and Herbert A.
Liberman
2. Pharmaceutics
The Science of dosage form
design By Michael E. Aulton
3.Cooper and Gunn Tutorial
Pharmacy By S. J. Carter B
4.Dispensing for Pharmaceutical
Students By S. J. Carter B. Pharm
5. Modern Pharmaceutics
By Gilbert and Christopher T. Rhodes
6.Pharmaceutical dosage form and drug
delivery system
By Howard. Ansel
7. Remington, The science and
practice of Pharmacy.
8.American
Pharmacy By
Sprowls
9. Bently,Pharmaceutical
Science
10. Introduction to
Pharmaceutics By A. K. Gupta
11. Physical Pharmacy, By
Martin
12. Dispensing of medication by
Martin
■ Intended mainly for oral administration
■ - Most commonly are disk shaped with
convex surfaces
■ - Available in special shape like round,
oval, oblong, cylindrical, square,
triangular
■ - Widely used solid dosage form
because they offer a number of
advantages to the patient, prescriber,
manufacturer and manufacturing
pharmacist
Advantages of Tablets
■ - Offer the greatest capabilities of all the oral
dosage forms for the greatest dose
■ precision and the least content variability
■ - easy to be swallowed or administered
■ - easy to handle and carry by the patient
■ - economical, manufacturing cost are
comparatively low while the manufacturing
speed is quite high
■ - are the most stable with respect to physical,
chemical and microbiological attributes, among
the different dosage forms
■ - Bitter, unpleasant taste and nauseous
odour of medicaments can be easily masked by
administering in the form of coated tablet
■
- attractive and elegant in appearance
- product identification is probably the easiest
variety of shapes and colours of tablets that are
possibleof the
because
■ - are the lightest and the more compact of all
dosage forms
■ - are generally the easiest and the cheapest
to pack and transport
■ - the release rate of the drug from the
tablets can be easily tailored to meet specific
pharmacological requirement
■ - don’t require any measurement of dose
■ - are divided into halves, quarters by
drawing lines during manufacture to facilitate
breakage whenever a fractional dose is
required
■ - lend themselves to certain special release
profile such as enteric or delayed release
Disadvantages
■ 1. Some drugs are difficult to compress into tablet
due to their amorphous nature or low density
character
■ 2. Drugs with high doses are difficult to
formulate as tablet dosage form
■ 3. Bitter tasting drug with objectionable odour
require special treatment like coating or
encapsulation which may increase the cost of
the dosage form
■ 4. Drugs that are sensitive to oxygen or
atmospheric moisture may also require special
coating as well as costly packaging which may
increase the overall cost of finished product
■ 5.Drugs with poor wetting and slow dissolution
properties are difficult to convert into tablets
which will not provide full drug
bioavailability.
■ 6. Drugs that are absorbed from the upper part
of GIT may also pose bioavailability problems if
administered in tablet dosage form
■ 7. Drugs that are liquid at room temperature can
not be formulated in tablet dosage form
■ 8. A major disadvantage with respect to
convenience of patients is the difficulty of
swallowing specially by children and ill patients
■
Essential qualities of a good
tablets
■ 1. They should be accurate and uniform in
weight
■ 2. The drugs should be uniformly distributed
throughout the tablets
■ 3. The size and shape should be reasonable
for easy administration
■ 4. The tablets should not be too hard that it
may not disintegrate in the stomach
■ 5. There should not be any incompatibilities
■ 6. They should be chemically and physically
stable during storage
■ 7. They should not break during
transportation or crumble in the hands of
the patient
■ 8. They should be attractive in appearance
■ 9. There should not be any manufacturing
defects like cracking, chipping or discolouration
■ 10. After disintegration it should be
dissoluted and release the drug readily
■ 11. They should be easy and economical in
production.
■
Types and classes of tablets
■ Oral Tablets for ingestion
■ 1. Compressed tablets or
standard compressed tablets
(C.T)
■ 2. Multiple compressed
tablets (M.C.T)
■ a. Layered tablets
■ b. Compressed coated tablets
■ 3. Enteric coated tablets
(E.C.T)
■ 5. Delayed action
tablets(D.A.T)
■ 6. Sugar coated tablets
(S.C.T)
■ 7. Film Coated Tablets(F.C.T)
■ 8. Chocolate coated tablet (C.
C.T)
■ 9. Effervescent tablet(E. V. T)
■ 10.Chewable tablets
Tablets used in the Oral
cavity
■ 1. Buccal tablets
■ 2. Sublingual tablets
■ 3. Lozenges or troches
■ 4. Dental Cones
■ Tablets administered by other
routes
■ 1. Implantation tablets
■ 2.Vaginal tablets
Tablets used to prepare
solutions
■ 1. Effervescent tablets
■ 2. Hypodermic tablets
(H.T.)
■ 3. Dispensing tablets
(D.T)
■ 4. Tablet triturates (T.T.)
Granulation
■ Granulation is the process in which
primary powder particles are made to
adhere to form larger, multiparticulate
entities called granules.
■ Pharmaceutical granules typically have
a size range between 0.2 and
4.0mm depending on their
subsequent use.
■ However, in the majority of the cases,
this will be for the production of tablets
and capsules., when granules will be
made as an intermediate product and
have a typical size range between
Reasons for granulation.
■ 1. To prevent segregation of the constituents
of the powder mix
■ Segregation means demixing and are mainly
due to particles size, density and shape
differences.
■ 2. To improve the flow properties of the mix
■ 3. To improve the compaction properties of
the mix
■ 4. Other reasons:
■ a. To reduce the hazard associated with the
generation of toxic dust that may arise during
handling.
■ b. To reduce the possibility of caking when
stored at least for hygroscopic products
■ c. More convenient for storage or shipment. Since
granules being more denser than the parent
solvents used in granulation include ,
Water, ethanol, Isopropanol, ether alone or in combination.
Water is commonly used because,
■ a. Economical and ecological reason
i. Cheaper ii. easily available iii. non
inflammable so expensive safety
precaution such as the use of flameproof
equipment need not be taken
■ Disadvantage of water:
a. Adversely affect drug stability, causing
hydrolysis of susceptible products
b. Possibilty for microbial growth
c. Need a larger drying time than do organic
solvents. Thus increases the
length of the process and again may affect
stability because of the extended exposure to
heat
d. most drugs are water sensitive, so organic
solvent must select in that case.
Granules are characterise by;
■ a. Size and size distribution b.
Shape c. Surface area d.Density
e.Strength and Friability f. Flow
propeties and Angle of repose g.
Compaction properties
■ Method of Tablet preparation
a. Wet granulation
b. Dry granulation or
precompression
c. Direct compression
Processing steps commonly required on the various
Tablet Granulation Preparation Techniques
Processing Wet Dry Direc
steps t
Rawmaterials X X X
Weigh X X X
Screen X X X
Mix X X X
Compress(Slug) X
Wet mass X
Mill or wet X
sieve
Dry X
Mill or dry X X
sieve
Mix X X
Compress X X
Direct compression
■ A few crystalline drugs such as sodium chloride,
sodium bromide, potassium chloride and aspirin
may be compressed directly.
■ A number of materials are available which are
directly compressible and which can serve as
tablet diluents for direct compression.]
■ Examples, Directly compressible
microcrystalline cellulose (Avicel),
Dicalcium Phosphate (emcopress),
anhydrous and spray dried lactose,
modified starch (starch 1500) directly
compressible grades of sucrose, sorbitol,
mannitol and dextrose
Advantages
■ “Direct compression is the most
economical of the three methods in term
of time , labour, and equipment.
■ The bioavailability of the drug is usually
better due to absence of adhesive
binding agents.
■ The elimination of moistening and drying
stages prevents many of the stability
problems(such as. Hydrolysis of the drug,
microbial growth in the product etc)
associated with moist granulation process
1. High cost of the directly compressible
materials
2. Differences in particle size and bulk density
between the drug and diluent may lead to
stratification within the granulation. The stratification
may then result in poor content uniformity of the drug
in the compressed tablet.
The stratification and resultant content uniformity
problem are of special problem with low dose drugs
3. A large dose may present problems with
direct compression if it is not easily
compressible. To facilitate compression, non-
compressible large-dose drugs which are
usually restricted to about 30% of a direct
compression formula, could require an
amount of diluent so large that the resultant
■ 3. In some instance the direct
compression diluent may interact with
the drug. A good example of such a
reaction is that which occurs between
amine compounds and spray dried
lactose, a yellow colour produced.
■ 4. Because of the dry nature of direct
compression, static charge buildup can
occur on the drug during routine
screening and mixing, which may prevent
a uniform distribution of the drug in the
granulation.
WET GRANULATION METHOD
■ It is the most widely used method for
making tablet. The problems in this
methods:
■ -multiple step processes, need long
time, expensive
■ -Stability problems for water sensitive
and heat sensitive drugs
■ - Possibility for microbial growth
■ The steps used for making tablets in this
process are shown in the table 2.
Granulators used to prepare wet granules
are;
■ A. Shear(Low)granulator
■ It is the traditional method of making
granules. Three to four equipments are
used in this method;
■ 1. Mixer machine to mix the ingredients,
however when the formulation containing
two to three components with equal
amounts can be avoided this equipment
and can be done in the planetary mixer
(2)
■ 2. Planetary mixer to make the wet
mass or paste
■ 3. Oscillating granulator to make
the wet granules
■ 4.Dryer to dry the wet granules
(Tray dryer or fluidized dryer)
■ Advantages
■ -the process is not very sensitive to
changes in the characteristics of the
granules ingredients
■ -the end point of the massing process can
often be determined by inspection
■ Disadvantages
■ -Multiple steps
■ -Long duration
■ -the need for several pieces of
equipments
■ -the high material loss that can be
incurred because of transfer stages
■ This type of granulator(Diosna
Fielder) are used extensively in
pharmaceuticals.
■ It consists of a stainless steel mixing
bowl
(1) mounted in the vertical position.
■ A high speed mixer blade ( a three
bladed main impeller) (2), revolves
around the bottom of the bowl. The
blade fits over a pin bar at the
bottom of the mixing bowl, which
powers the blade. The blade is
specially constructed to discharge
material from getting under it.
■ The mixer also contain high
■ A pneumatic discharge port (4)
provides the unit with automatic
discharge
■ The unit is provided with a lid (5) with
three openings: one to accommodate a
spray nozzle, a second larger opening for
an air exhaust sleeve (6), and a third
opening for a viewing point.
■ The units are also equipped with an
ammeter on the control panel(7), which
may be employed to determine the end
point of the granulation operation.
■ The mixer also contain high speed chopper
blade (3) which functions as a lump and
agglomerate breaker.
■ A pneumatic discharge port (4) provides the
unit with automatic discharge
■ The unit is provided with a lid (5) with three
openings: one to accommodate a spray nozzle,
a second larger opening for an air exhaust
sleeve (6), and a third opening for a viewing
point.
■ The units are also equipped with an ammeter
on the control panel(7), which may be
employed to determine the end point of the
granulation operation.
Principle
■ The unmixed dry powders are placed in
the bowl and mixed by rotating impeller
for a few minutes.
■ Granulating liquid is then added via a port
in the lid of the granulator while the
impeller is turning. The granulating fluid is
mixed into the powders by the impeller.
■ The chopper is usually switched on when
the moist mass is formed, as its function
to break up the wet mass to produce a
bed of granular material.
■
■ When a satisfactory granule has been
produced, the granular product is
discharged, passing through a wire mesh
which breaks up any large aggregates,
into a bowl of a fluidized bed dryer. Or is
shifted into a tray dryer.
■ Typical time sequences for the use of a
Diosna mixer are as follows:
■ a. Mixing 2 minutes or less b.
granulating 8 mins. Or less c,
Discharge 1 minutes.
■ A variation of the Diosna type of
design is the Collette-Gral mixer.
This is based on the bowl and
overhead drive of the planetary
mixer but the single paddle is
replaced by two mixing shafts.
■ One of these carries three blades,
which rotate in the horizontal plane
at the base of the bowl and the
second carries smaller blades which
acts as the chopper and rotate in the
horizontal plane in the upper regions
of the granulating mass. Thus the
operation principle is similar.
■ Advantage and disadvantage
Mixing, massing and granulation are all
performed within a few minutes in the
same piece of equipment.
■ The process needs to be controlled
with care as the granulation
progresses so rapidly that a usable
granule can be transformed very
quickly into an unusable over massed
system. Thus it is often necessary to
use a suitable monitoring system to
indicate the end of the granulation
process
C.Fluidized Bed Granulators
In his case, Heated and fluidized air is blown or
sucked through the bed of unmixed powders
to fluidize the particles and mix the powder in
the granulating chamber.
Granulating fluid is pumped from a reservoir
through a spray nozzle positioned over the
bed of particles and sprayed on to the bed of
powders.
The fluid causes the primary particles to adhere
when the droplets and powders collide.
Escape of material from the
granulation chamber is prevented
by exhaust filters, which are
periodically agitated to reintroduce
the collected material into the
fluidized bed.
Sufficient liquid is sprayed to
produce granules of the required
size , at which point the spray is
turned off but the fluidizing air
continued.
■ -Single unit system. ( all the granulation processes
which require seperate equipment in the conventional
method are performed in one unit thus saving labour,
costs, transfer losses and time.
■ -The process can be automated once the conditions
affecting the granulation have been optimized.
■ Disadvantages
■ -Initially expensive and optimization of
process (and product) parameter
affecting granulation needs extensive
development work, not only during initial
formulation work but also during scale
up from development to production. This
long and very product specific
development process has proved to be a
problem with fluidized-bed granulation in
the pharmaceutical industry.
■ -Fluidized bed systems may not provide
adequate mixing of powder components.
In fact there is a tendency for demixing to
occur when there are disparities in
particle size or density in the materials
being processed.
■ -Particles with granulating agent on their
surface tend to stick to the equipment
filters, reducing the effective filter surface
area, causing product loss, and increasing
clean up difficulties.
Table 1. Apparatus, Process and product
variables
■ Apparatus parameters:
■ Air distribution plateShape of granulator
body, Nozzle heigh, tPositive and
negative pressure operation, Scale up
■ Process parameters
■ Bed load, Fluidizing air flow rate, Fluidizing
air temperature, Fluidizing air humidity,
Automation Nozzle type, spray angles,
Spraying regime,liquid flow rate,
Automizing air flow rate, Automizing air
pressure, Droplet size
■ - Special attention is also needed
for safety in any fluid bed
processor. Dust explosion can occur
in a fluid bed dryer, with flammable
solvents or with dry materials that
develop static charges. All
production size fluid bed equipment
must contain explosion relief
panels.
■
■ Materials parameters
■ Type of binder, quantity of binder,
binder solvent, concentration of
granulating solution, Temperature of
granulation solution, Starting
materials
■ Fluidization, Powder hydropobicity
Advantages of wet granulation
■ 1. The cohesiveness and compressibility of
powders is improved due to the added binder
that coats the individual powder particles
■ 2. Drugs having a high dosage and poor flow
and /or compressibility must be
granulated by wet method to obtain suitable
flow and cohesion for compression.
■ 3. Good distribution and uniform content for
soluble, low dosage drugs and colour additives
are obtained if these are dissolved in the binder
solution.
■ 4. A wide variety of powder can be possessed
together in a single batch and in so doing , their
individual physical characteristics are altered to
facilitate tabletting.
■ 5. Bulky and dusty powders can be
handled without producing a great deal
of dust and air borne contamination
■ 6. It prevents segregation of components
of a homogeneous powder mixture during
processing
, transferring, and handling.
■ 7. The dissolution rate of an insoluble
drug may be improved by wet granulation
with the proper choice of solvent and
binder
■ 8. Controlled release dosage form
can be accomplished by the selection
of a suitable binder and solvent.
Disadvantages
■ 1. Because of large no of processing steps, it
requires a large area with temperature and
humidity
■ 2. It requires a number of pieces of
expensive equipment
■ 3. It is time consuming, especially the
wetting and drying equipment
■ 4. There is a possibility of material loss during
processing due to transfer of materials from one
unit to
another
■ 5. There is a grater possibility of cross
contamination than with direct compression
method
■ 6. It presents material transfer problems
involving the processing of sticky masses
■
Defects in Tablets (Tabletting
Problems)
1. Capping and Lamination
■ Capping refers to the partial or complete
separation of the top or bottom portions
of the tablet. Lamination is the
separation of a tablet into two or more
layers.
■ Mostly these problems become
apparent immediately after
compression but sometimes these may
occurs hours or even days latter.
■ The main causes of capping and
lamination are:
■ a. Entrapment of air in the
granulation b. Excessive fines of
powder
■ c. Excessive drying of granules d.
Excessive compression force e.
High speed of machine
f. use of defective dies and punches
■ These problems can be overcome by :
■ a. Reducing the percentage of fines in
the granulation b. Maintaining
desired moisture level in the granulation
■ 2. Picking and sticking:
■ The term picking signifies the removal of
material from the surface of the tablet
and its adherence to the punch face. This
problem is more prominent where the
monogram on the punch surface have
sharp angles as exemplified by letters ‘A’,
‘B’, ‘M’ etc.
■ Sticking refers to the adherence of
tablet material to the die wall. This
result in difficulty in the ejection of
tablet which may cause further chipping
of tablets edges.
■ Picking and sticking is usually caused due to :
■ a. Improper designing of engraved or
monogrammed punches b.
■ Poorly maintained punch faces c. Use of worn
out punches and dies d. Under dried granules
e. Lack of lubricants with antiadherent
properties f. Low melting ingredients in the
granulation
The problems may be overcomes by:
■ a. Proper designing of punches b. Chrome
plating of punch surfaces c. Adequate drying of
granules d. Using antiadherents like talc,
magnesium stearate and colloidal silica e.
Substituting low melting ingredients with high
melting point ones or refrigeration of the
■ 3. Molting:
■ It refers to the unequal distribution of
colour on the surface of tablet. This
problem can be traced to :
■ a. Differences in the colour of the drug
and excipients b.Migration of a dye to
the surface off granulation during
drying
■ c. Improper distribution of colourants d.
Large particle size of the dye /lake
■ e. Non uniform particle size
distribution of tablet granules
■ The problems can be avoided:
■ a. Using a dye that can mask the colour
of all the ingredients in the formulation
b. Using the alternate solvent system for
the granulation c. Reducing the drying
temperature of the granules d. Reducing
the particle size of granules e. Using
dyes and lakes of very fine particle size.
■ 4. Weight variation
■ This problem is encountered when the
tablets do not have a uniform weight.
The problem is usually associated with:
■ a. Poor flow of granules b. Segregation of
the different components of the
granulation c. Non uniform particle size
distribution of granules d. Presence of
excessive fines e.Significant differences
in the densities of different components
of granulation f. Incorrect lubrication of
granulation
■ The problem can be overcome by:
■ a. Using granules of uniform particle size
distribution b. Using ingredients of
approximately the same densities c.
Decreasing the fines d. Using proper
concentration of lubricants, glidants etc.
e. Replacement of defective punches
■ 5. Hardness variation
■ This problem is encountered when the
tablets vary significantly in their
hardness. The problem occurs due to the
same reasons as weight variation.
Hardness of a tablet depends on the
weight of the materials being
compressed and the space between the
upper and lower punches during the
compression. If the weight of the
materials or the distance between the
punches varies, the hardness will also
vary.
■ 6. Double Impression
■ This problem is generally evident in
cases where the lower punches have a
monogram or other engravings on them.
On some machines, the lower punch is
free to drop and travel for a short
distance before ascending to eject the
tablet out of the die. During the free
travel period, the punch may rotate
and make a new lighter impression on
the bottom of the tablet, resulting in a
double impression.
■ Similar problem may be
encountered in machines that
have a precompression stage
before the actual compression.
■ This problem can be overcome by
controlling the undesirable
movement of the punches.
■
