Tablets

1
Tablets
Prepared by
Mr. Sahebro S. Boraste

TABLETS
 Tablets are solid unit dosage forms in which one usual
dose of the drug has been accurately placed.
 Tablets are the solid dosage form containing
medicament or medicaments, usually circular in shape
and may be flat or biconvex.
 Tablet is defined as a compressed unit solid dosage
form containing medicaments with or without
excipients.
 According to the Indian Pharmacopoeia,
Pharmaceutical tablets are solid, flat or biconvex
dishes, unit dosage form, prepared by compressing a
drugs or a mixture of drugs, with or without diluents.
2

GENERAL PROPERTIES OF TABLETS
 A tablet should have elegant product identity while free
of defects like chips, cracks, discoloration, and
contamination.
 Should have sufficient strength to withstand mechanical
shock during its production packaging, shipping and
dispensing.
 Should have the chemical and physical stability to
maintain its physical attributes over time.
 The tablet must be able to release the medicinal agents
in a predictable and reproducible manner.
 Must have a chemical stability over time so as not to
follow alteration of the medicinal agents.
3

ADVANTAGES OF TABLET
 They are a unit dose form, and they offer the greatest
capabilities of all oral dosage forms for the greatest dose
precision and the least contentvariability.
 Their cost is lowest of all oral dosage forms
 They are the lightest and most compact of all oral dosage
forms.
 They are in general the easiest and cheapest to package
and ship of all oral dosage forms
 Product identification is potentially the simplest and
cheapest, requiring no additional processing steps when
employing an embossed or monogram on punch face.
4

 Product identification is potentially the simplest and
cheapest, requiring no additional processing steps when
employing an embossed or monogram punch face.
 They lend themselves to certain special release profile
products, such as enteric or delayed-release products.
 They are better suited to large-scale production than
other unit oral dosage forms.
 They have the best combined properties of chemical,
mechanical and microbiologic stability of all the oral
dosage forms.
 They may provide the greatest ease of swallowing with
the least tendency for hang-up above the stomach.
5

DISADVANTAGES OF TABLET
 Some drugs resist compression into dense compacts,
owing to their amorphous nature or flocculent, low-
density character.
 Bitter-tasting drugs, drugs with an objectionable odor,
or drugs that are sensitive to oxygen or atmospheric
moisture may require encapsulation or entrapment
prior to compression.
 Drugs with poor wetting and slow dissolution and large
doses becomes difficult to formulate.
6

TYPES OF TABLET
Type of tablet Class of tablet
Oral tablets for ingestion 1. Standard Compressed tablet,.
2. Multiple compressed tablet
Layered tablet
Compression coated tablet
3. Chewable tablet
4. Sugar coated tablet.
5. Film coated
6. Repeat action tablet
7. Delayed/ Controlled release
8. Controlled release tablet.
Tablets in oral Cavity 1. Buccal tablet
2. Trouches and lozenges
3. Dental cones
Tablets by other routes Implants and vaginal Tablet
Tablets to prepare solution 1. Effervescent tablet
2. Dispensing tablet
3. Hypodermic tablet
4. Tablet triturate
7

TYPES OF TABLETS
Compressed tablets
 Compressed tablets are formed by compression of
powdered, crystalline, or granular materials into the
required geometry by the application of high pressures,
utilizing compression machines.
 In addition to the Active Pharmaceutical Ingredient(s)
(APIs), compressed tablets usually contain a number of
pharmaceutical
 Examples of compressed tablets include tablets for oral,
buccal, sublingual, or vaginal administration
8

 Compressed tablets are clinically used to provide
systemic administration of therapeutic agents either in an
uncoated state (i.e., in their simplest form) or in a coated
state.
 These tablets are designed to provide rapid disintegration
in the gastric fluid, allowing rapid release of the drug and,
its systemic absorption.
9

SUGAR-COATED TABLETS
 These are compressed tablets that have been coated
with concentrated sugar solution to improve patient’s
compliance, increase aesthetic appeal, mask
objectionable tastes or odours, increase stability
and/or modify the release of therapeutic agent(s).
 Sugar coating was once quite common but lost
commercial appeal due to the time and expertise
required in the coating process, the increase in size
and weight of coated tablets, high cost of process
validation and shipping
10

 Also, they permit separation of incompatible
ingredients between coating and core, and this fact has
been widely utilized in preparing many multivitamin and
multivitamin mineral combinations.
 Time consuming and requires skilled labour.
 Examples of sugar-coated tablets include Reasulf
tablets – dried ferrous sulphate BP 200mg (Reagan
Remedies Ltd.), Advil – Ibuprofen tablet BP 200mg
(Pfizer Consumer Healthcare), Ebu-200 – Ibuprofen
tablet BP 200mg
11

FILM-COATED TABLETS
 Film-coated tablets are conventional tablets coated with a thin
layer of polymer (e.g., hydroxypropyl methylcellulose,
hydroxypropyl cellulose) or a mixture of polymers (e.g.,
Eudragit E100) capable of forming a skin-like film.
 The film is usually coloured and also impacts the same
general characteristics as sugar coating with the added
advantage of being more durable, less bulky, and less time-
consuming to apply.
 By its composition, the coating is designed to break and
expose the core tablet at the desired location in the
gastrointestinal tract.
 Coating compositions contains one or more polymers, which
usually includes a plasticizer for the polymer and possibly a
surfactant to facilitate spreading, in solution from in a organic
solvent.
12

 After coating there is little increase in weight of tablet
compared to sugar coating.
 Controlled release tablets can be prepared by film coating.
 They have less aesthetic appeal as compared to sugar
coated tablet.
 Examples of Film-coated tablets include Curefenac 100 –
Diclofenac potassium USP 100mg (Unicure Pharmaceutical
Ltd), Valsartan 320mg Film-coated Tablets (Actavis UK Ltd),
etc
13

EFFERVESCENT TABLETS
 Effervescent tablets are uncoated tablets that generally
contain organic acids (such as tartaric or citric acid) and
sodium bicarbonate in addition to the medicinal
substance or API.
 They react rapidly in the presence of water by releasing
carbon dioxide which acts as a disintegrator to produce
either a drug suspension or an aqueous solution.
 These tablets are prepared by compressing granular
effervescent salts (organic acid and bicarbonate) with
the medicinal substances.
 They have capability of producing clear solutions, such
tablets also produce a pleasantly flavored car- bonated
drink, which assists in maskingthe taste of certain drugs
14

 The disadvantage of the effervescent tablet, is related to
the difficulty of producing a chemically stable product.
Even the moisture ir the air during product preparation
may be adequate to initiate effervescent reactivity
 Effervescent tablets are specially packaged in hermetic-
type foil pouches or are stack-packed in cylindric tubes
with minimal air space
15

ENTERIC-COATED TABLETS
 Enteric-coated tablets are compressed tablets that have
delayed-release properties.
 They are coated with polymeric substances (such as
cellulose acetate phthalate/cellulose acetate butyrate;
hydroxypropylmethylcellulose succinate; and methacrylic
acid copolymers)
 They resist solution in gastric fluid but disintegrate and
allow drug dissolution and absorption in the intestine.
 Primarily employed when the drug substance is
inactivated or destroyed by gastric acid or is particularly
irritating to the gastric mucosa or when bypass of the
stomach substantially enhances drug absorption.
16

 All enteric coated tablets which remain intact in the
stomach but release drug in the upper intestine t
 .Not all delayed-action tablets are enteric or are intended
to produce the enteric effect.
 Example of enteric-coated tablets includes Lofnac 100 –
Diclofenac sodium delayed-release tablet USP 100mg
(bliss GVS Pharma Ltd), Ecotrin tablets and caplets
(GlaxoSmithKline
17

CHEWABLE TABLETS
 Chewable tablets are big sized tablets which are difficult
to swallow and thus, are chewed within the buccal cavity
prior to swallowing.
 They are especially useful for administration of large
tablets to children and adults who have difficulty
swallowing conventional tablets or antacid formulations
in which the size of the tablet is normally large.
 Most common example is chewable Aspirin tablet for
children's.
 Chewable tablets are not conventionally used if the drug
has issues regarding taste acceptability.
18

 Useful for formulation of antacid tablets because they
have large dose making them difficult to swallow.
 Antacid tablet when chewed provide better
neutralization of acid because they are broken down to
ideal particle size .
19

BUCCAL AND SUBLINGUAL TABLETS
 Buccal and sublingual tablets are small, flat, oval tablets
that are intended to be dissolved in the buccal pouch
(buccal tablets) or beneath the tongue (sublingual
tablets) for absorption through the oral mucosa to
produce a systemic effect.
 Drugs absorbed by this route avoids first pas
metabolism. Drugs decomposed by gastric environment
like steroids and hormones are well absorbed by tis
route.
20

 They rapid onset of action as compared if tablet
swallowed.
 Buccal and sublingual tablet are formulated with bland
excipients to prevent saliva stimulation, which prevents
drugs from swallowing and causes it absorbed from oral
mucosa.
 These tablet should not disintegrate immediately rather
slowly dissolve over period of 15-30 min to provide
effective absorption through oral mucosa.
21

LOZENGES OR TROCHES
 These are disc-shaped solid preparations containing
medicaments and generally a flavouring substance in a
hard candy or sugar base.
 They are intended to be slowly dissolved in the oral
cavity, usually for local effects in mouth and throat.
 They are commonly used to treat sore throat and control
cough & common cold.
22

 They may contain local anesthetic, antiseptic,
antibacterial, demulcents, astringents and antitussive
agents.
 They are made with drug in flavored hard candy sugar
base by compression or fusion candy molding process.
 They are designed not to disintegrate but slowly dissolve
or erode in mouth for 30 min or less.
23

TABLET TRITURATES
 Tablet triturates are small, usually cylindrical, moulded,
or compressed tablets containing small amounts of
usually potent drugs mixed with a combination of
sucrose and lactose or any suitable diluent.
 prepared from moist material, using a triturate mould to
give shape of cut sections of a cylinder.
 Since tablet triturates must completely and rapidly
dissolve in water, only a minimal amount of pressure is
applied during their manufacture.
 One of the problems in manufacture of this tablet is to
find a lubricant that is completely water-soluble.
 A typical example of tablet triturate is Nitroglycerine
sublingual tablet.
24

HYPODERMIC TABLETS
 Hypodermic tablets are soft, readily soluble tablets that
were originally used by physicians in extemporaneous
preparation of parenteral solutions.
 These tablets are dissolved in a suitable vehicle (water
for injections) and administered by parenteral route.
 Hypodermic tablets are no longer used in most countries
due to the difficulty in achieving sterility 25

 These tablets were previously used by physicians in
rural areas as physicians needed to carry many vials of
such tablet and one bottle of sterile water for injection to
prepare many injectable.
 Such tablets not used today because of its sterility issue
and availability of modern medicines
26

Dispensing Tablets
 These tablets are added in given quantity of water to
produce solution of given drug conc.
 These tablets commonly include mild silver protienate,
bichloride of mercury and quaternary ammonium
compounds with all totally soluble excipients.
 These tablets are not used today because of they may
prove highly toxic and hazardous if mistakenly
swallowed.
 Label should indicative to prevent oral consumption.
27

MULTIPLE COMPRESSED TABLETS
 Multi-compressed tablets are tablets that are composed
of two or more layers.
 These tablets are prepared by subjecting the fill material
to more than one compression cycle
 The result may be a multiple-layer tablet or a tablet
within a tablet, the inner tablet being the core and the
outer portion being the shell
 This process is best used when separation of active
ingredients is needed for stability purposes
 Multiple compressed tablets can also be used when
there is a need to mask the bitter taste of a drug
28

MULTIPLE COMPRESSED TABLETS
 There are three subclasses of multiple compressed tablets :
compression coated tablets, layered tablets and inlay
tablets
Compression Coated Tablets
 Referred to as dry-coated tablets or press-coated tablets,
are tablets with two parts; internal core and surrounding
coat.
 These tablets are prepared by feeding previously
compressed tablets into a special tablet press and
compressing another granulation layer around a preformed
tablet core
29

 These tablets can also be used to separate incompatible
drug substances (one in the core and the other in the
coat);
 in addition, they can provide a means of giving an
enteric coating to the core tablets.
30

Layered Tablets
 They are tablets composed of two or more layers of
ingredients.
 prepared by compressing additional tablet granulation on a
previously compressed granulation to form two-layered or
three-layered tablets, depending on the number of separate
fills.
 Each layer may contain a different medicinal agent,
separated for reasons of physical or chemical
incompatibility, staged drug release.
31

Inlay tablets
 Inlay tablets, popularly known as dot tablets with a
partially surrounded core.
 Tablet core is completely surrounded by the coating, its
top surface is completely exposed
 Prepared by feeding previously compressed tablets into
a prefilled die cavity of Stokes, Colton, or Kilian
machines.
 When compressed, some of the coating material is
displaced to form the sides.
 Used in sustained-release preparations to reduce the
size and weight of the tablet
32

IMMEDIATE-RELEASE TABLETS
 Immediate-release tablets are tablets designed to
disintegrate and release their medication with no special
rate-controlling features, such as special coatings and
other techniques.
 This is the most common type of tablet and examples
include, chewable, effervescent, sublingual and buccal
tablets.
33

RAPID-RELEASE TABLETS
 Also called rapidly dissolving tablets, rapidly disintegrating
tablets, orally-dispersible tablets, quick disintegrating
tablets, mouth dissolving tablets, fast disintegrating tablets,
fast-dissolving tablets.
 characterized by disintegrating or dissolving in the mouth
within 1 minute, some within 10 seconds.
 Prepared using very water-soluble excipients for rapid
disintegration or dissolution without chewing.
34

EXTENDED-RELEASE TABLETS
 Sometimes called controlled-release tablets, prolonged-
release, delayed release or sustained release tablets
 Designed to release their medication in a predetermined
manner over a prolonged period of time.
 release the drug in a relatively steady, controlled manner.
35

VAGINAL TABLETS/ VAGINAL INSERTS
 Vaginal tablets are uncoated, bullet-shaped, or ovoid
tablets designed for vaginal administration.
 They are prepared by compression and are shaped to fit
tightly on plastic inserter devices.
 Following insertion, retention and slow dissolution of the
tablet occur, releasing the medicaments to provide the
local pharmacological effect.
 Vaginal tablets may also be used to provide systemic
absorption of therapeutic agents
36

IMPLANTS
 long-acting sterile tablets designed to provide continuous
release of drugs, often over a period of months or a year.
 They are placed subcutaneously for systemic or local
delivery.
 Implants are mainly used for the administration of hormones
such as testosterone steroids for contraception.
 They usually contain rate-controlling excipients in addition
to the active ingredient(s).
 Examples of implantation tablets include Implanon –
etonogestrel (Organon), Disulfiram Tablet for Implantation
37

EXCIPIENTS USED IN TABLETS
 Ideal characteristics of Excipients.
1. They must be nontoxic and acceptable by regulatory
agencies in all countries.
2. They must be commercially available in an acceptable
grade in all countries where the product is to be
manufactured.
3. Their cost must be acceptably low.
4. They must be physiologically inert.
5. They must be physically and chemically stable with
drugs and other tablet components.
6. They must be free microbial load.
7. They must be color-compatible (not produce any off-
color appearance).
8. They must have no deleterious effect on the
bioavailability of the drug
38

DILUENTS
 Diluents are fillers to make up the required bulk of the tablet
when the drug dose is not sufficient to produce this bulk.
 Very small tablets are difficult to swallow, handle and
compression, such problems can be handled by adding
diluents.
 Diluents that exist in their common salt form as hydrates,
containing bound water as water
of crystallization, may not be excellent for very water-
sensitive drugs.
 Certain amine containing drugs have incompatibility with
diluent lactose in presence of stearates.
39

Lactose
1. Most widely used diluent in tablet formulation.
2. has no reaction with most drugs, whether used in the hydrous or
anhydrous form.
3. Anhydrous lactose has the advantage over lactose in that it does not
undergo the Maillard reaction.
4. Maillard reaction interaction of certain amine drugs with the
commonly used diluent lactose, in the presence of a metal stearate
lubricant (such as magnesium stearate).
5. Th anhydrous form, picks up moisture at elevated humidity . Such
tablets may have to be carefully packed.
6. Grades of lactose are commonly available commercially available
60 to 80 mesh (coarse)
80- to 100-mesh (regular) grade
7. spray-dried lactose is one diluent available for direct
compression.with moisture content of 3%.
8. Spray dried lactose has also good flow property, but shows maillard
reaction with amine containing drugs.
40

STARCHES
 Starch made from corn, wheat or potatoes, is occasionally
used as a tablet diluent.
 USP grade of starch has poor flow and compression
properties with moisture content of 11 and 14%.
 Sta-Rx 1500 is directly compressible starch with free-
flowing, directly compression property.
 It may be used as a diluent, binder & disintegrating agent
 Sta-Rx 1500 contains 10 % moisture.
 Two hydrolysed starches are available Emdex & Celutab,
which are basically 90- 92 % dextrose & 3-5 % maltose
with 8-10 % mositure
 These are free flowing and directly compressible.
41

 Dextrose:
1. Used as tablet diluent.
2. Available as Cerelose (Hydrous & anhydrous) when low
moisture content is needed.
3. Lactose is replaced with dextrose to avoid darkening in
some tablets.
 Mannitol
1. Most expensive tablet diluent.
2. because of its negative heat of solution, its slow solubility,
and its pleasant feeling in the mouth,t is
widely used in chewable tablets.
3. Mannitol formulations have poor flow characteristics and
require fairly high lubricant levels
42

 Sorbitol
1. Sorbitol is an optical isomer of mannitol and is sometimes
combined in mannitol formulations to reduce diluent cost.
2. sorbitol is hygroscopic at humidities above 65%.
 Sucrose/sugar
1. sucrose-based diluents are available under tradenames
Sugartab (90 to 93% sucrose plus 7 to 10%invert sugar),
DiPac (97% sucrose plus 3%modified dextrins), and Nu Tab
(95% sucrose and 4% invert sugar with a small amount of
corn starch and magnesium stearate).
2. Above sugars are directly compressible but have tendency to
absorb moisture at elevated humidity.
3. Used in chewable tablets.
4. Avoided for patients with diabetes.
43

 Microcrystalline cellulose
1. Available under tradename Avicel, is a direct
compression material.
2. Available in 2 grades PH 101(powder) & PH 102
(granules)
3. It produces cohesive compacts.
4. the material also acts as a disintegrating agent.
5. relatively expensive material when used as a diluent in
high concentration it is mixed with other diluents.
44

DILUENTS USED IN TABLETS
Diluent brand name
Calcium carbonate Pharma-carb, calcarb
Dibasic calcium Phosphate Cyfos, calstar, Emcompress
Calcium sulfate Cal-tab
Microcrystalline cellulose (MCC) Avicel, Emocel,Vivacel
Dextrose Tabfine
Fructose Fructofin
Lactose monohydrate Fastflo, lactochem, zeparox
Maltodextrin Glycidex, lycatab,
Maltose Advantose
Mannitol Pearlitol
Sorbitol,
Starch Pharmagel, pre-jel, starch 1500,
starx 1500
Sugar Dpiac, Nutab
Xylitol Xylifin, xylitab
45

BINDERS
 Binders are added either dry or in liquid form during wet
granulation to form granules or to promote cohesive
compacts.
 Acacia and tragacanth are natural gums used in
conc. ranging from 10 to 25% alone or in combination.
 Natural gums have the disadvantage of variation in their
composition and performance are are usually fairly heavily
contaminated with bacteria.
 When these materials are used in wet granulation the
granules are dried quickly to reduce microbial
proliferation
46

 Gelatin
1. Gelatin is natural protein and is sometimes used in
combination with acacia.
2. It is used in solution form, and forms tablets equally as
hard as acacia or tragacanth.
Starch
1. Starch paste has been one of the most common
granulating agents prepared by heating dispersion of
starch in water
2. During the heating, the starch undergoes hydrolysis to
dextrin and to glucose.
3. Starch paste is translucent rather than clear (which would
indicate virtually complete conversion to glucose).
4. produces cohesive tablets that readily disintegrate.
47

 . Liquid @u- cose, which is a 50% solution in water, is a
fairly common wet granulating agent. Its properties are
similar to those of sucrose solutions, which are commonly
employed in concentrations between 50 and 74%.
Thèse sugar solutions are capable of producing wet
granulations, which when tabletted, produce hard but
somewhat brittle compacts. These materials have the ad-
vantage of being low-cost adhesives.
48

Glucose:
1. 50 % glucose solution in water is used.
2. These produces hard tablets but brittle tablets.
3. These are low cost binders but may cause bacterial
proliferation.
Modified natural gums:
1. Alginates and celluose derivatives ( methyl cellulose,
HPMC, HPC) are commonly used binders.
2. Can also be used for direct compression.
3. HPC as alcohol solution produces anhydrous adhesive.
4. Ethyl cellulose also used in alcoholic solution.
5. PVP produces adhesive compacts in both aqueous and
alcoholic solution.
49

DISINTEGRANTS
 A disintegrant is added to facilitate a breakup or
disintegration of the tablet when it contacts water in the
gastrointestinal tract.
 Disintegrants may function by drawing water into the tablet,
swelling, and causing the tablet to burst apart. Which further
helps in dissolution of the drug and bioavailability.
 Starch and starch derivatives are low cost material & are
most commonly used.
 Starch used in 5-20 % conc.
 Modified starches Primogel & Explotab which are low
substituted carboxymethyl starches in low conc. (1-8 %).
 Pregelatinzed starches used in 5 % Conc.
50

DISINTEGRANTS IN TABLET
Disintegrant Brand name Conc. Used
Microcrystalline cellulose Avicel, Emocl , Vivacel Up to 10%
Crosscarmellose sodium Ac-Di-sol, solutab 0.5 – 5 %
Crosspovidone Kollidon CL 2-5%
Magnesium aluminium
silicate
Veegum 2-10%
Methyl cellulose Celacol, methocel 2-10 %
Polacrilin potassium Ameberelite 2 – 10%
Povidone Kollidon, plasdone 0.5 – 5 %
Sodium alginate Manucol 2- 10 %
Sodium starch glycolate Explotab ,primogel 2-10%
Starch 2-10%
Pregelatinized strach Lycatb, pharma-gel,
pre-jel, sepsitab
5- 10%
51

 The disintegrants can be mixed in 2 stages
1. Intragranular: during formation of granules: prior to wetting
with granulating fluid.
2. Extrgarnular: second mixing stage before compression of
granules.
 Extragranular quickly disintegrates the granules, where as
intragranular breaks the granules in to fine product.
52

LUBRICANTS ANTIADHERENTS AND GLIDANTS
 A material that is primarily described as anti-adherent is
typically lubricant with some glidant property.
 Lubricants reduce friction during tablet ejection between
walls of tablet and wall of die cavity.
 Anti-adherents reduces sticking of granules or powder to
the faces of punches or die wall.
 Glidants promote flow of granules or powder by reducing
friction between particles.
 Lubricants are added in final step of mixing before tablet
compression
53

LUBRICANTS USED IN TABLET
Lubricant Brand name Conc. Used
Calcium stearate 0.5- 2 %
Hydrogenated vegetable oil Lubritab, sterotex 0.5 -5 %
magnesium lauryl sulfate 1- 6 %
magnesium stearate 1-2 %
FEG 4000 or 6000 Macrogols, carbowax 0.25- 5 %
Sodium lauryl sulfate Empicol 1-2 %
Stearic acid 1-3 %
Talc 1-10 %
Zinc stearate 0.5-2 %
Glidant Brand name Conc. Used
Magnesium carbonate 1-3 %
Cellulose, powdered Elcema, solka 1-2 %
Magnesium silicate 0.5-2 %
Silicon dioxide Aerosil 0.05-0.5 %
Talc 1-10 %
Calcium silicate 0.5-2 %
Magnesium oxide 1 -3 %
54

 Mineral oil when used as lubricant by fine spray may produce oil spots.
 The most widely used lubricants is stearic acid and its derivatives.
 Calcium and magnesium stearate are the most common salts
employed.
 Talc is probably the second most commonly used tablet lubricant,
 talc should be added carefully added in any formulation containing a
drug whose breakdown is catalyzed by the presence,1% iron.
 Hydrophobic lubricant posses problem of slow dissolution and
bioavailability.
 Talc is used as glidants at 5 % conc., corn starch at 5-10 %
55

COLORS, FLAVOURS AND SWEETENERS
 The use of colors and dyes in tablet is for product identification and to
improve product elegance & acceptance.
 Two forms of color have typically been used in tablet preparation.
These are the FD&C and D&C dyes which are applied as solutions,
typically in the granulating agent and the lake forms of these dyes.
 colored tablets should be checked for resistance to color changes on
exposure to light.
 Flavors are usually limited to chewable tablets or other tablets
intended to dissolve in the mouth.
 Flavors that are water-soluble & have little acceptance in tablet
making because of their poor stability.
 Flavor oils are added to tablet granulations in solvents or by
dispersing on clays and other absorbents, or are emulsified in
aqueous granulating agents.
56

 Use of sweetener is limited to chewable tablet or mouth dissolving
tablets.
 Mannitol is 72 % sweet as sugar.
 Saccharin is 500 times sweeter than sugar but it is reported to be
carcinogenic.
 Aspartame is expected to largely replace saccharin. But has
disadvantage stability issue in the presence of moisture.
57

TABLET MANUFACTURING METHODS
1. Wet granulation
2. Dry granulation
3. Direct compression.
58
DIRECT COMPRESSIONDRY GRANULATIONWET GRANULATION
Milling/ScreeningMilling/ScreeningMilling/Screening
BlendingPre-blendingPre-blending
CompressionSlugging/roller
compaction
Addition of binder
Dry screeningScreening of wet mass
Blending of lubricantDrying of the wet granules
CompressionScreening of dry granules
Blending of lubricant (and
disintegrant)
Compression

59
DIRECT COMPRESSIONDRY GRANULATIONWET GRANULATION
1. Fewer processing steps
– blending and
compression -reduced
processing time
2. Processing without
moisture and heat –
fewer stability problems
3. Rapid and most direct
method of tablet
compression
4. Changes in dissolution
less likely on ageing
since there are less
formulation variables
1. Improved flow by
increasing particle size
2. Improved uniformity of
powder density
3. Improved cohesion
during compression
4. Granulation without
addition of liquid
1. Improved flow by
increasing particle size
and sphericity
2. Uniform distribution of
API, colour etc. –
improved content
uniformity
3. Good for bulky
powders, less dust and
environmental
contamination
4. Lower compression
pressure, less wear
and tear on tooling

GRANULATION
 Granulation is the process in which primary powder particles are
made to adhere to form larger, multiparticle entities called granules.
 Pharmaceutical granules typically have a size range between 0.2 and
4.0 mm, depending on their subsequent use.
Reasons of Granulation
1. To prevent segregation of the constituents of the powder mix
Powder
Segregated powder
GranulesGranulation
Sieving
Uniform granules
60

2. To improve the flow properties of the mixture.
3. To improve the compaction characteristics of the mixture.
4. Reduce the hazard of toxic dust powders.
5. Hygroscopic material may form a cake if stored as a powder.
granulation may reduce as they to absorb some moisture and yet retain
their flow ability because of their size.
6. More convenient for storage
61

WET GRANULATION
1. Wet granulation involves the massing of a mix of dry
primary powder particles using a granulating fluid.
2. The fluid contains a solvent which must be volatile so
that it can be removed by drying, and be nontoxic.
3. The granulation liquid may be used alone or, more
usually, as a solvent containing a dissolved binding
agent which is used to ensure particle adhesion once the
granule is dry.
4. In wet granulation method the wet mass is forced through
a sieve to produce wet granules which are then dried.
5. A subsequent screening stage breaks agglomerates to
uniform size 62

6. Granulating liquid may include water, ethanol and isopropanol or
in combination.
7. advantages of water is that it is non- flammable and economical but
may cause stability issue with water sensitive drugs.
8. Organic solvents are used when water sensitive drugs are handled,
they require lesser drying times but are flammable.
63

MECHANISM IN WET GRANULATION
1. Adhesion and cohesion forces in the immobile liquid films
between individual primary powder particles.
2. Interfacial forces in mobile liquid films within the granules.
3. The formation of solid bridges after solvent evaporation.
4. Attractive forces between solid particles
64

STAGES IN WET GRANULATION
 Addition of granulating liquid to powder mass is characterized by series
of stages given below.
A. Pendular
B. Funicular
C. Capillary
D. Droplet 65

1. During initial stage when particles are wetted, liquid film is formed on
their surface and combine to produce discrete liquid bridges at
contact points.
2. This state is called pendular state where surface tension and
negative capillary pressure provides cohesive force.
3. As the liquid content increases, several bridges may coalesce
(combine) giving rise to funicular state, further increasing the strength
of moist granules.
4. When further liquid is added and mass is kneaded void spaces in
granules are completely eliminated.
5. Here bonding is affected by interfacial forces at granule surface and
by negative capillary pressure through out liquid filled space called
capillary state.
6. Further addition of liquid results in droplet formation where particles
are held together by surface tension but intragranular forces are
weaker.
66

 Liquid plays important role granulation process . Liquid bridges
developed between particles and tensile strength f bonds increases
with addition of liquid.
 The surface tension and capillary pressure are responsible for granule
formation and strength.
 Once granulating fluid is asses mixing continues until uniform
dispersion is attained and binder is activated.
67

DRY GRANULATION
 This method is used when dose of drug is high for direct
compression, heat & moisture sensitive.
 In this powder blend is forced in to dies of large capacity press and
compacted by flat punches to masses called slugs.
 These slugs are then screened or milled to form granules with good
flow property than original powder mixture.
 When the material is subjected to compaction pressures, it causes
strengthening of bonds that hold tablet together.
 The granules prepared by this method are then subjected to
compression to form tablets.
 For large scale compression granulation Roller compacter is used 68

EQUIPMENT FOR DRY GRANULATION
Roller Compactor
Example: Chilsonater roller compactor
 On large scale compression granulation can be performed
on a specially designed machine called as roller
compactor.
 It is capable of producing as much as 500 kg / hour or
more of compacted ribbon like material, which can be
screened in to granules for compression.
 It utilizes two rollers revolving towards each other.
 By using hydraulic force the machine is capable of
exerting known pressures on powdered material that flows
between the rollers.
 After passing through rollers the compacted mass i.e slugs
are screened or milled for production of granules 69

70
Compaction force is controlled
by three variables
1. The pressure exerted on
compaction rolls.
2. The rotational speed of
compaction rolls.
3. Rotational speed of feed
screw

DIRECT COMPRESSION
 In this method directly compressible diluents are compacted with little
difficulty and may compress quantities of drugs when mixed them.
 Diluents like microcrystalline cellulose, spray dried lactose,
coprocessed sugars like Dipac, Nutab, pregelatnised starches like
starx 1500 etc are used for direct compression.
Advantages of direct compression:
1. Simple process and low labor requirements.
2. Being dry process, deterioration of API.
3. Particles in tablet break to original particles rather than granular
aggregates.
4. Increased surface area for dissolution is achieved.
71

Disadvantages
1. Differences in bulk density and particle size of drug and diluent
may lead to poor content uniformity of drug in tablet.
2. Large dose drugs are poor candidates for direct compression as
addition of diluents results in to larger tablets which are difficult to
swallow.
3. May cause interaction with drugs. Ex: spray dried lactose with
amine containing drug causes discoloration of tablets.
4. Being dry method, may cause static charge up on mixing and
screening
72

Advanced Granulation Techniques
Types of granulation techniques.
1. Dry granulation
2. Moisture activated dry granulation
3. Pneumatic dry granulation
4. Wet granulation
5. Melt granulation (or) Thermo plastic granulation
6. Thermal adhesion granulation.
7. Steam granulation.
8. Foam granulation

1. Dry granulation:
 The Dry granulation process involved initially conversion of powdered blend
tablet in to slugs (or) compact masses which are then screened to form
uniform sized fine granules.
 The dry granulation process is suitable for
 Moisture sensitive drugs.
 Drugs undergo degradation at high temperature.
Advantage:
 Less time taking.
Disadvantage:
 It produces dust.
 Type of binding agent utilized in dry granulation:
 Starch [Star RX 500, Star RX 1500.].

2. MOISTURE ACTIVATED DRY GRANULATION (MADG)
 In this method moisture is used to activate the granules formation but the
granules drying step is not necessary due to moisture absorbing material
such as MCC.
 The moisture-activated dry granulation process consists of two steps, a)
a)wet agglomeration of the powder mixture
b) moisture absorption stages.
 A small amount of water (1–4%) is added first to agglomerate the mixture of
the API, a binder, and excipients.
 Moisture absorbing material such as MCC and potato starch is then added to
absorb any excessive moisture.
 After mixing with a lubricant, the resulting mixture can then be compressed
directly into tablets.
 MCC, potato starch, or a mixture of 50% of each can be used as moisture
absorbing material.

Moisture Activated Dry Granulation

3.PNEUMATIC DRY GRANULATION:
 It is a novel dry method for production of granules by automatic or
semiautomatic method.
 It is compatible with other technologies, such as sustained release, fast
release, coating .
 It is suitable for thermolabile and moisture sensitive drugs,
 Enables flexible modification of drug load, disintegration time and tablet
hardness .
 The granules of pneumatic dry granulation technology have excellent
properties compared to wet granulation dry granulation and direct
compression .
 At the same time the granules show both high compressibility and flow ability

 PDG dry granulation technique involves use of roller compaction with
proprietary air classification method.
 This method extraordinary granules with greater flowability & Compressibility
 Here granules are produced by mild compaction force to form compacted
mass, compromising mixture of fine particles & granules.
 The fine particles are seperated from granules by fractionating chamber by
entraining in gas stream( Pneumatic system).
 The fine particles are again transferred to roller compacter for immediate
processing.
 This technique produce free flowing granules with tensile strength of 0.5
Mpa.

Advantages of Pneumatic dry granulation
1. Good granulation results even at high drug loading have been
achieved even with materials known to be historically difficult to
handle,
2. Faster speed of manufacturing compared with wet granulation,
3. Lower cost of manufacturing compared with wet granulation,
4. The system is closed offering safety advantages due to low dust
levels and potential for sterile production or handling of toxic
materials,
5. The end products are very stable - shelf life may be enhanced,
6. Little or no waste of material,
7. Scale-up is straightforward,
8. The granules and tablets produced show fast disintegration
properties, offering the potential for fast release dosage forms

4. FREEZE GRANULATION TECHNOLOGY
1. Swedish Ceramic Institute (SCI) developed an technique freeze
granulation (FG) – which enables preservation of the homogeneity from
suspension to dry granules.
2. By spraying a powder suspension into liquid nitrogen, the drops (granules)
are instantaneously frozen.
3. In a subsequent freeze-drying the granules are dried by sublimation of the
ice.
4. The result will be spherical, free flowing granules, with optimal homogeneity

Besides, high degree of granule homogeneity, FG offers several other
advantages.
1. Control of granule density by the solids content of the suspension.
2. Mild drying prevents serious oxidation of non-oxides and metals.
3. No cavities in the granules.
4. Low material waste (high yield).
5. Small (50–100 ml suspension) as well as large granule
6. quantities can be produced to equal quality.
7. Easy clean of the equipment (latex binder can be used).
8. Possibility to recycle organic solvents

5. FOAM GRANULATION
 Foam granulation technique involves addition of liquid binders as aqueous
foam
 The advantages of foamed binder addition conventional binder addition
method includes-
1. No spray nozzle is used
2. Improve process robustness
3. Less water required for granulation
4. Time efficient drying
5. Cost effective
6. Uniform distribution of binder
7. No over wetting
8. Applicable for water sensitive formulation

6. MELT GRANULATION TECHNOLOGY
 Melt Granulation process has been widely used in the pharmaceutical
industry for the preparation of both immediate and controlled release
formulations.
 In this process the granules are obtained by the addition of either or molten
binder or a solid binder which melts during the process .
 This process has also been widely accepted for the enhancement of
dissolution profile and bioavailability of poorly water soluble drugs by forming
solid dispersion.

Requirements of melt granulation:
 Generally, an amount of 10–30% w/w of meltable binder, with respect to that
of fine solid particles, is used.
 A Meltable binder suitable for melt a granulation has a melting point typically
within the range of 50– 100_C.
 Hydrophilic Meltable binders are used to prepare immediate-release dosage
forms
 while the hydrophobic Meltable binders are preferred for prolonged-release
formulations.
 The melting point of fine solid particles should be at least 20°C higher than
that of the maximum processing temperature.

Advantage of melt granulation:
1. Neither solvent nor water used.
2. Fewer processing steps needed thus time
3. consuming drying steps eliminated.
4. Uniform dispersion of fine particle occurs.
5. Good stability at varying pH and moisture levels.
6. Safe application in humans due to their non-swellable and water insoluble
nature

7. STEAM GRANULATION
 Steam granulation” is the modification of wet granulation.
 Here steam is used as a binder instead of water. .
 In this method of granulating particles involves the injection of the required
amount of liquid in the form of steam.
 This steam injection method, which employs steam at a temperature of about
150° C.,

Advantages
 Uniformly distributed in the powder particles
 Higher diffusion rate
 Results in more spherical granule formation
 ·Higher dissolution rate of granules because of larger surface area generated
 Time efficient
 Environment friendly
 No health hazards to operator
 Regulatory compliance
 Maintains sterility
Disadvantages
 Requires special equipment for steam generation and transportation
 Requires high energy inputs.
 Thermolabile materials are poor candidates
 More safety measure required
 ·Not suitable for all the binders.

PELLETIZATION
 Pelletization technique help in the formation of spherical
beads or pellets having a diameter 0.5 -1.5 mm .
 These pelletized have gained popularity considerably
because of their distinct advantages
1. such as ease of capsule filling because of better flow
properties of the perfectly spherical pellets;
2. enhancement of drug dissolution;
3. ease of coating; sustained, controlled, or site-specific
delivery of the drug from coated pellets;
4. uniform packing;
5. even distribution in the GI tract and less GI irritation
89

TECHNIQUES OF PELLETIZATION
90
1. Extrusion and Spheronization
2. Hot melt extrusion
3. Solution/ suspension layering
4. Powder layering
5. High shear palletization
6. Freeze palletization
7. Cryo-pelletization
8. Crystal co-agglomeration
9. Wet spherical crystallization
10.spherical crystallization

EXTRUSION AND SPHERONIZATION
91
1. Shaping wet mass in cylinders is called Extrusion.
2. Breaking the extrudates and rounding the particles in to spheres.
Dry Mixing Wet mixing Extrusion
Spheronization
Drying
Screening

1) Dry mixing
 Dry mixing of all ingredients is done to get homogeneous powder
dispersion or mixer using different types of mixers like twin shell
blender, high shear mixer, tumbler mixer and planetary mixer.
2)Wet massing
 Wet massing of powder dispersion is done to produce a sufficient
plastic mass for extrusion. This granulation is similar to a conventional
wet granulation .
 The granulation endpoint is determined by the behavior of the wetted
mass during the extrusion operation.
 The most commonly used granulator is planetary mixer or sigma blade
mixer or high shear mixer and Hobart mixer.
92

3) Extrusion
 This is the third step in the process.
 Extrusion a method of applying pressure to a mass until it flows
through an opening.
 In this process the wetted mass is passed through the extruder to form
rod shaped particles of uniform diameter.
 The granulation solvent serves as the binding agent to form the
granules and as the lubricating during the extrusion operation.
 The diameter of the extruder screen opening directly controls the
diameter of the extrudate.
 The granulation solvent serves as the binding agent to form the
granules and as the lubricating during the extrusion operation
93

4) Spheronization
This operation has been divided into three stages
 such as breaking of the cylindrical segments or extrudate,
 agglomeration of the broken segments
 and smoothing of the particles.
Breaking of the cylindrical segments occurs due to the interaction of the
extrudate with the rotating plate, stationary wall and other extrudate
particles
 Agglomeration occurs when the small fragments produced during the
breaking stage are picked up by the larger granules during smoothing.
 Spherical particles are created during smoothing stage by generating
rotational motion of each granule about its axis in constantly changing
planes
94

5) Drying
 To get desired moisture content in pellets a drying stage is required.
 The pellets can be dried at room temperature or at elevated
temperature in a tray drier/ oven or in a fluidized bed drier.
6) Screening
 Screening may be necessary to achieve the desired size distribution,
and for this purpose sieves are used.
 In case of pellets prepared by extrusion spheronization, screening is
essentially required after manufacturing, in order to avoid pellets
having high size polydispersity index
95

TABLET COMPRESSION
96
 Compression
Compression means a reduction in the bulk volume of a material
as a result of the removal of the gaseous phase (air) by applied
pressure.
 Consolidation
Consolidation is an increase in the mechanical strength of
material resulting from particle-particle interactions.
 Compaction
Compaction of powders is the general term used to describe the
situation in which these materials are subjected to some level of
mechanical force.

98
Figure: Various intraparticulate & inter-particulate air spaces in
powder bed

Load
Deformation
If elastic If plastic
MECHANISMS OF COMPRESSION OF PARTICLES
Load
Load Load

STEPS IN TABLET COMPRESSION
Complete cycle of compression occurs in four stages:
Stage 1:
 Top Punch is withdrawn from die by upper cam.
 Lower punch is low in the die, so powder falls through the hole
in the die to fill it.
Stage 2:
 Bottom punch moves up adjust the powder weight.
 It raises & expels the excess powder.
Stage 3:
 Top punch is driven in to die by upper cam& bottom punch is
lowered by lower cam.
 Both punches heads passes between heavy rollers to
compress the powder.
100

Stage 4:
 Top punch is withdrawn by upper cam.
 Lower punch is pushed up with ejects the tablet out of the die
Stage 5: return to stage 1.
101

MECHANISM OF TABLET COMPRESSION
Process of tablet compression involves phase like
1. Initial repacking or particle rearrangement
2. Deformation
3. Fragmentation
4. Bonding
5. Deformation of solid body
6. Ejection.
102

1. Particle rearrangement
 Occurs at low pressure & depends on particle shape & size.
 Reduction in volume of powder bed takes place in to close packing
structures.
 Bulk density of powder increases as fine powder in granules fill the
voids of larger particles resulting in rearrangement.
 Further increase in pressure makes movement of particles impossible
inducing deformation,
103

2. Deformation
 When particles are closely packed with no voids, further increase in
compression causes deformation at the point of contact.
104

105
Elastic deformation
 Elastic deformation is described as densification of particles due to
movement of cluster of molecules or ions that forms particles.
 Particles can completely or partly modify their shape by elastic
deformation.
 Deformation completely disappears after removal of force.
 Ex: acetyl salicylic acid.
Plastic deformation
 Deformation that does not completely recover after removal of force is
called plastic deformation.
 It occurs by sliding of molecules along the slip of planes with in particle.
 Deformation beyond elastic deformation leads to plastic deformation.
 Yield stress: force required to produce plastic deformation

3. Fragmentation
 Under high pressure deformed particles may fragment resulting in new
clean surfaces which have potential bonding areas.
 Fragmentation further lead to densification by infilteration of smaller
fragments in to voids.
 In some materials fragmentation do not occur because the stress is
released by plastic deformation.
106

4. Bonding of particles
 Bonding due to addition of liquid.
 Bonding due to addition of binder
 Due to solid bridges.
 Intermolecular & electrostatic forces.
 Mechanical interlocking.
Bonding is governed by several theories like
 The mechanical theory
 The intermolecular theory
 Liquid surface film theory
107

 The mechanical theory
1. The theory proposes that under high pressures individual particles
undergo plastic/elastic/ or brittle deformation and edges of particles
intermesh deforming mechanical bond.
2. It occurs between irregular shape particles & increases with number
of contact points between particles.
3. Not a major bonding mechanism in tablets compression
 Intermolecular theory
1. Molecules/ions at surface of solids have unsatisfied forces(surface
free energy) which interact with other particle at true contact.
2. Under pressure molecules at true contact between new clean
surfaces are close enough that wander Waal forces interact to
consolidate the particles.
3. Materials with plenty OH groups create hydrogen bonds between
molecules.
108

 Liquid surface film theory
1. Here bonding occurs due to presence of thin film which may be
consequence of fusion or solution at surface of particles induced by
energy of compression.
2. Solid bridges: Occurs when two solids are mixed at interface to form
a continuous solid phase.
3. Hot welding: under applied pressure edges of the contact points
between particles undergo melting due to generation of heat incase
of low melting point solids which up on solidification forms solid
bridges.
4. Cold welding: it is a contact welding process where joining takes
place with out fusion at interface of solid surface. Here bonding takes
place by generation of attractive forces when surface of two particles
come close to each other
109

5. Deformation of solid body
 On further increase of pressure non bonded solids are consolidated
towards a limiting density by plastic/ elastic deformation.
6. Ejection:
 Finally lower punch rises ejecting the tablet upward
 There is continued residual die wall pressure & considerable energy is
expanded due to die wall friction.
 After pressure is removed there is lateral pressure on die wall.
 After ejection tablet under go elastic recovery with increase in volume
as it is removed from die.
110

CAPPING
112
• The upper or lower segment of the tablet separates horizontally,
either partially or completely from the main body and comes off
as a cap, during ejection from the tablet press, or during
subsequent handling.
Reason:
• Due to the air–entrapment in a compact during compression,
and subsequent expansion of tablet on ejection of a tablet
from a die.

113
Causes Remedies
1. Large amount of fines in
the granulation
Remove some or all fines through 100 to 200
mesh screen
2. Too dry granules or low
moisture content
Moisten the granules, add
hygroscopic agents. Ex:
Sorbitol, Methylcellulose or
PEG-4000
3. Not thoroughly dried
granules.
Dry the granules properly.
4. Insufficient amount of
binder or improper
binder.
Increasing the amount of binder OR
Adding dry binder such as pre-
gelatinized Starch, Gum acacia,
powdered Sorbitol, PVP.
5. Insufficient or improper
lubricant.
Increase the amount of lubricant or
change the type of lubricant.
6. Granular mass too cold to
compress firm.
Compress at room temperature.
7. Poorly finished dies Polish dies properly. Investigate other
steels or other materials.
8. Deep concave punches or
beveled-edge faces of
punches.
Use flat punches.
9. Lower punch remains
below the face of die
during ejection.
Make proper setting of lower punch
during ejection.
10 High turret speed. Reduce speed of turret

LAMINATION
114
 Separation of a tablet in to two or more distinct horizontal
layers.
 Reason:
1. Air–entrapment during compression and subsequent
release on ejection.
2. The condition is exaggerated by higher speed of turret.

115
Causes Remedies
1. Large amount of fines in
the granulation.
Remove some or all fines through 100 to 200 mesh screen.
2. Too dry granules or low
moisture content .
Moisten the granules, add hygroscopic agents. Ex:
Sorbitol, Methylcellulose or PEG-4000.
3. Not thoroughly dried
granules.
4. Insufficient amount of
binder or improper
binder.
Increasing the amount of binder ORAdding dry binder
such as pre-gelatinized Starch, Gum acacia,
powdered Sorbitol, PVP.
5. Insufficient or improper
lubricant.
Increase the amount of lubricant or change the type
of lubricant.
6. Rapid relaxation of the
peripheral regions of a
tablet, on ejection from a
die.
Use tapered dies, i.e. upper part of the die bore has
an outward taper of 3° to 5°.
7. Rapid decompression. Use pre-compression step. Reduce turret speed and
reduce the final compression pressure.

STICKING
 Tablet material adhering to the die wall.
 Filming is a slow form of sticking and is largely due to
excess moisture inthe granulation.
 Reasons
Improperly dried or improperly lubricated granules.
116

117
Causes Remedies
1. Granules not dried properly. Dry the granules properly. Make
moisture analysis to determine
limits.
2. Too little or improper
lubrication.
Increase or change lubricant.
3. Too much binder Reduce the amount of binder or use
a different type of binder.
4. Hygroscopic granular
material.
Modify granulation and
compress under controlled
humidity.
5. Oily or way materials Modify mixing process. Add an
absorbent.
6. Concavity too deep for
granulation.
Reduce concavity to optimum.
7. Too little pressure. Increase pressure.
8. Compressing too fast. Reduce speed.

PICKING
118
• Small amount of material from a tablet is sticking to and being
removed off from the tablet-surface by a punch face.
• The problem is more prevalent on the upper punch faces than
on the lower one
Reasons:
 Picking is of particular concern when punch tips have engraving or
embossing letters.
 Granular material is improperly dried.

Causes Remedies
1. Excessive moisture in granules. Dry properly the granules, determine
optimum limit.
2. Too little or improper lubrication. Increase lubrication; use colloidal
silica as a ‘polishing agent’,
3. Low melting point substances,
may soften from the heat of
compression and lead to picking.
Add high melting-point materials.
Use high meting point lubricants.
4. Low melting point medicament
in high concentration.
Refrigerate granules and the entire tablet
press.
5. Too warm granules when
compressing.
Compress at room temperature..
6. Too much amount of binder. Reduce the amount of binder, change
the type or use dry binders.
7. Rough or scratched punch faces. Polish faces to high luster.
8. Embossing or engraving letters on punch
faces such as B, A, O, R, P, Q, G.
Design lettering as large as possible.
Plate the punch faces with chromium to
produce a smooth and non-adherent face.
9. Bevels or dividing lines too deep. Reduce depths and sharpness.
10. Pressure applied is not enough; too soft
tablets.
Increase pressure to optimum. 119

CRACKING
 Small, fine cracks observed on the upper and lower central surface of
tablets, or very rarely on the sidewall are referred to as ‘Cracks’.
Reason:
 Observed as a result of rapid expansion of tablets, especially when deep
concave punches are used.
120
Causes Remedies
1. Large size of granules. Reduce granule size. Add fines.
2. Too dry granules. Moisten the granules properly and
add proper amount of binder.
3. Tablets expand. Improve granulation. Add dry binders.
4. Granulation too cold. Compress at room temperature.
5. Tablet expands on ejection due to
entrapment of air
Use tapered die

BINDING
 Sticking of the tablet to the die and does not eject
properly out of the die.
 Tablets adhere, seize or tear in thedie.
 A film is formed in the die and ejection of tablet is
hindered.
 With excessive binding, the tablet sides are cracked and it may
crumble apart.
Reason:
 Usually due to excessive amount of moisture in granules.
 lack of lubrication and/or use of worn dies.
121

122
Causes Remedies
1. Too moist granules and extrudes
around lower punch.
2. Insufficient or improper lubricant. Increase the amount of lubricant or use a
more effective lubricant.
3. Too coarse granules. Reduce granular size, add more fines,
and increase the quantity of lubricant.
4. Too hard granules for the lubricant
to be effective.
Modify granulation. Reduce granular size.
5. Granular material very abrasive
and cutting into dies.
If coarse granules, reduce its
size. Use wear-resistant dies.
6. Granular material too warm, sticks
to the die.
Reduce temperature.
Increase clearance if it is extruding.
7. Poorly finished dies. Polish the dies properly.
8. Rough dies due to abrasion,
corrosion.
Investigate other steels or other materials or
modify granulation.
9. Undersize dies, too little
clearance
Use proper size dies & increase clearance
10. Too much pressure of press Reduce pressure , modify granulation.

MOTTLING
 Unequal distribution of color on atablet, with light or dark spots.
Reasons:
 Colored drug, whose color differs from the color of excipients
used for granulation of a tablet.
123
Causes Remedies
1. A coloured drug used along with
colourless or white- coloured
excipients.
Use appropriate colourants.
2. Improperly mixed dye,
especially during ‘Direct
Compression’.
Mix properly and reduce size if it is of
a larger size to prevent segregation.
3. A dye migrate to surface of
granulation while drying
Change the solvent system, change
the binder, reduce drying
temperature.

DOUBLE IMPRESSION
 Involves only those punches, which have a monogram or other
engraving on them.
 If the upper punch is uncontrolled, it can rotate during the short
travel to the final compression stage and create a double
impression
Reasons:
 During compression the tablet receives imprint of the punch.
 The lower punch freely drops and travels uncontrolled for a
short distance before riding up the ejection cam to push the
tablet out of the die
 Now during this free travel, the punch rotates and at this point,
the punch may make a new impression on the bottom of the
tablet, resulting in ‘double impression 124

Causes Remedies
• Free rotation of either upper punch or
lower punch during ejection of a tablet
• Use keying in tooling, i.e. inset a key
alongside of the punch, so that it fits the
punch and prevents punch rotation.
• Newer presses have anti-turning devices,
which prevent punch rotation.
125

CHIPPING
126
• Breaking of edges of tablets as the tablet leaves the press or during
subsequent handling and coating operations.
Reasons
• Incorrect machine setting
Reasons Remedy
1. Sticking on punch faces Dry the granules properly or increase
lubrication.
2. Too dry granules. Moisten the granules to
plasticize. Add hygroscopic
substances.
3. Too much binding causes
chipping at bottom.
Optimize binding, or use dry binders.

EVALUATION OF TABLETS
 Non-official tests
1. General appearance
 Organoleptic properties
 Size & shape.
2. Hardness.
3. Friability.
Official tests
1. Weight Variation
2. Content uniformity
3. Dissolution
4. Disintegration.
127

NON OFFICIAL TEST
General Appearance:
 The general appearance of a tablet, its visual identity and
overall “elegance” is essential for consumer acceptance,
for control of lot-to-lot uniformity.
 Appearance of a tablet involved the measurements of a
tablet’s:
1. Size
2. Shape
3. Color
4. Odor
5. Taste
6. Surface texture
128

 Shape & size
• Measured by micrometer or sliding caliper scale
• Tablet thickness should be controlled with in ± 5 %
variation of standard value.
 Organoleptic properties
• Many pharmaceutical tablets use color as a vital means of
rapid identification and consumer acceptance
 The color of a product must be uniform within a single
tablets.
129

HARDNESS
130
1. Tablets require a certain amount of strength, or hardness and
resistance to friability, to withstand mechanical shocks of
handling in manufacture, packing and shipping.
2. Hardness is also called crushing strength.
 Tablet hardness tester are:-
1. Monsanto tester
2. Pfizer tester
3. Strong-cobb tester
4. Erweka tester
5. Schleuniger tester
• 5-8 Kg/cm2 for standard compressed,
effervescent, dispersible tablet.
• More than 8-12 Kg/cm2 for sustained
& controlled release tablets.

FRIABILITY
 The friability test is official in USP but not in BPand IP.
 Friability tester is known as the Roche friabilator
 Tablet hardness is not an absolute indicator of strength
since some formulations, when compressed into very hard
tablets.
131
Procedure:
1. Pre-weighed tablets are placed in friabilator.
2. The equipment is operated at 25RPM for 4
min. (100 Revolutions) dropping at distance
of 6 inches.
3. Tablets are then dusted and reweighed. %
friability is calculated as per formula
Initial weight – final weight X 100
Final weight
The % friability of tablets should be less than
1 %

WEIGHT VARIATION
132
 Done routinely to ensure that tablet contains proper amount of drug.
 As per USP 20 tablets are weighed individually and calculating their
average weight, then individual weight of tablet is compared with
average weight. The value of weight variation is expressed in
percentage using formula.
weight variation = Individual weight – average weight X 100
average weight
 As per USP
S.
No.
Average weight of
tablets (mg)
Maximum percentage
difference allowed
1 130 or less ±10.0
2 130-324 ±7.5
3 More than 324 ±5.0

As per IP
Note:
1. According to USP, If we use 20 tablets then not more than 2 tablets
differ percent weight variation.
2. According to USP, If we use 10tablets then not more than 1 tablets
differ percent weight variation
133
S. No. Average weight of
tablets (mg)
Maximum percentage
difference allowed
1 84 or les ±10.0
2 84 - 250 ±7.5
3 More than 250 ±5.0

DISINTEGRATION TEST
 It is measure of time require to break tablet in to particles under given
set of conditions.
 It is done for tablets administered by mouth & not for tablets like
chewable, sublingual, buccal, lozeneges & effervescent tablet.
 It is done in simulated gastric or intestinal fluid.
 Disintegration test apparatus is used to study disintegration time.
134
Construction
• 6 tubes 3 inches long with 10 mesh screen.
• 1 liter beaker with simulated intestinal or
intestinal fluid.
• Temperature: 37 ± 2 0C.
• Upward downward movement: 5-6 cm
• Frequency: 28-32 cycles/min

USP method for uncoated tablet
1. Start the disintegration on 6 tablets
2. If one or two from 6 tablets fails to disintegrate completely with in 30 min,
repeat the same test on 12 tablets ( i.e whole test will consume 18 tablets).
3. Not less than 16 tablets should disintegrate completely with in time.
4. If more than 2 tablets (from 18) fails to disintegrate then the batch must be
rejected.
USP method for coated tablet
1. To dissolve coat , immerse tablet in distilled water for 5 min.
2. Put the tablet in apparatus containing water or HCL for 30 min, if not
disintegrated put in intestinal fluid.
3. If one or two tablet fails to disintegrate, repeat on 12 tablets, 16 out of 18
should completely disintegrate with in the time.
4. If two or more tablet does not disintegrate the batch should be rejected.
135

136
Tablet type IP BP USP
Standard Compressed
tablet(Uncoated)
15 Min 15 min 05 min
Sugar coated tablet 60 30 --
film coated tablet 30 30 --
Enteric coated tablet 1 Hr. 1-2 Hr. 2 Hr.
Effervescent Tablet < 3 min < 3 min < 3 min
Orodispersible Tablet < 1 min < 1 min < 1 min
Official standards

CONTENT UNIFORMITY
 The potency of tablets is expressed in the terms of grams, milligrams, or
micrograms of drug per tablet and is given as the label strength of the
product.
Content Uniformity test as per IP
1. Ten tablets are taken at random, there content of active ingredient is
determine in each of 10 tablets and the average value is calculated.
2. The sample passes the test is not more than one of the individual
value is the out side the limit of 85 to 115% of the average value and
no one is outside the limit of 75 -125 % of average value.
3. If two or three of the individual tablets are outside limits 85 to 115% of
the average value and the none is the outside the limit 75 to 125%.
4. The test is repeated using another 20 tablets.
 In the total sample of 30 tablets Not more than three of the individual
values are outsides the limit 85 to 115% and none is outside the
limits 75 to 125% of the average value.
137

DISSOLUTION TEST
 Dissolution is a process where solid solute goes in to solution.
 Or dissolution is amount of drug substance that goes I to
solution per unit time under standard condition of solid/liquid
interface, temp. & solvent composition.
 Dissolution profile of drug is important to determine
bioavailability of drug.
 Dissolution is carried out in
USP Dissolution Apparatus 1 ( Basket Type)
USP Dissolution Apparatus 2 ( Paddle Type)
 Tablet is placed in small wire mesh basket fitted to bottom of
shaft connected to speed variable motor which is immersed in
dissolution medium maintained at temp. of 37 ± 5 0C.
 The speed of the basket/ paddle is adjusted as per monograph
and samples are withdrawn at specific intervals to determine
amount od drug in solution.
138

Tablets

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Ähnlich wie Tablets

Ähnlich wie Tablets (20)

Mehr von sahebrao Boraste

Mehr von sahebrao Boraste (8)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

Tablets