TABLETS

Tablets may be defined as unit solid pharmaceutical

dosage forms containing one or more drug substances
with or without suitable diluents and have been
traditionally prepared by either compression or by
moulding method
 INTRODUCTION
• According to the Indian Pharmacopoeia Pharmaceutical tablets
are solid, flat or biconvex disc, unit dosage form, prepared by
compressing a drugs or a mixture of drugs, with or without
diluents.
• They vary in shape and differ greatly in size and weight,
depending on amount of medicinal substances and the intended
mode of administration.
• It is the most popular dosage form and 70% of the total medicines are
dispensed in the form of Tablet.
 ADVANTAGES
• Tablets are convenient to use and are an elegant dosage form.
• A wide range of tablet types is available, offering a range of drug release rates and
durations of clinical effect. Tablets may be formulated to offer rapid drug release or
controlled drug release, the latter reducing the number of daily doses required (and
in so doing increasing patient compliance).
• Tablets may be formulated to release the therapeutic agent at a particular site
within the gastrointestinal tract to reduce side effects, promote absorption at that
site and provide a local effect (e.g. ulcerative colitis). This may not be easily
achieved by other dosage forms that are administered orally.
• With the exception of proteins, all classes of therapeutic agents may be
administered orally in the form of tablets.
• Tablets may be formulated to contain more than one therapeutic agent (even if
there is a physical or chemical incompatibility between each active agent).
Moreover, the release of each therapeutic agent may be effectively controlled by
the tablet formulation and design.

• It is easier to mask the taste of bitter drugs using tablets than for other dosage
forms, e.g. liquids.

• Tablets are generally an inexpensive dosage form.

• Tablets may be easily manufactured to show product identification, e.g. exhibiting

the required markings on the surface.

• The chemical, physical and microbiological stability of tablet dosage forms is

superior to other dosage forms.
Disadvantages
■ The manufacture of tablets requires a series of unit operations and therefore
there is an increased level of product loss at each stage in the manufacturing
process.
■ The absorption of therapeutic agents from tablets is dependent on
physiological factors, e.g. gastric emptying rate, and shows inter patient
variation.
■ The compression properties of certain therapeutic agents are poor and may
present problems in their subsequent formulation and manufacture as
tablets.
■ The administration of tablets to certain groups, e.g. children and the elderly
may be problematic due to difficulties in swallowing. These problems may be
overcome by using effervescent tablet dosage forms.
 TYPES OF TABLETS

Tablets Tablets used to

Tablets Tablets used in
administered prepare
ingested orally oral cavity
by other route solution

1. Compressed tablet. 1. Buccal tablet. e.g. 1. Implantation 1. Effervescent tablet.

e.g. Paracetamol tablet Vitamin-c tablet tablet e.g. Dispirin tablet
2. Multiple compressed 2. Sublingual tablet. 2. Vaginal tablet. (Aspirin)
tablet e.g. Vicks Menthol e.g. Clotrimazole 2. Dispensing tablet. e.g.
3. Sustained action tablet tablet tablet Enzyme tablet
4. Delayed release tablet. 3. Troches or lozenges (Digiplex)
e.g. Enteric coated 4. Dental cone 3. Hypodermic tablets.
Bisacodyl tablet 4. Tablet triturates. e.g.
5. Sugar coated tablet. Enzyme tablet
e.g. Multivitamin tablet (Digiplex)
6. Film coated tablet.
e.g. Metronidazole
tablet
7. Chewable tablet.
e.g. Antacid tablet
 TABLETS INGESTED ORALLY
1. Compressed tablet: These are uncoated tablets made by compression of granules.
These provides rapid disintegration and drug release. e.g. Paracetamol tablet.
2. Multiple compressed tablet: These tablets are prepared to separate physically or
chemically incompatible ingredients or to produce repeat action or prolonged action
products. The ingredients of formulation are compressed into a core tablet and the
incompatible substance with other excipients are compressed over the previously
compressed core tablet.
3. Sustained action tablet: These tablets when taken orally release the medicament in a
sufficient quantity as and when required to maintain maximum effective concentration
of drug in the blood.
4. Enteric coated tablet: These tablets are coated with the material which does not
disintegrate in stomach but passes through as it is. i.e. enteric polymer e.g.:
Hydroxypropyl methyl cellulose phthalate etc. These tablets dissolve in intestine and
are site specific.
5. Sugar coated tablet: The compressed tablets with sugar coating are called
sugar coated tablets. It is done to mask the bitter and unpleasant taste and
odour of the medicament. It enhances the appearance and protects the drug
from atmospheric effects. e.g. Multivitamin tablet
6. Film coated tablet: These are the compressed tablets having a film coating of
film coating polymer like hydroxy propyl cellulose, ethyl cellulose , HPMC. It
also protects the formulation from atmospheric effects. These are tasteless,
have increase in tablet weight. e.g. Metronidazole tablet
7. Chewable tablet: These tablets are chewed in mouth and are broken into
small pieces. Disintegration time is reduced and rate of absorption increases.
Easily administered for infants and elderly persons. e.g. Antacid tablet
 ORAL CAVITY TABLETS
1. Buccal Tablets:
These tablets are to be placed in buccal pouch or between the gum & lip or cheek.
Tablet dissolve & disintegrated slowly & absorb directly.
2. Sublingual Tablet:
These tablets are to be placed under the longue. They dissolve & disintegrated
quickly & absorbed directly without passing into G.I.T. Buccal and sublingual
tablet should be formulated with bland excipients, which do not stimulate
salivation.
3. Lozenge tablet & troches:
These tablets are designed to exert a local effect in mouth or throat. These tablets
are usually used in treatment of sore throat or to control cough. The tablets are
usually used for drugs such as anaesthetic, antiseptic and antibacterial agent,
demulcent, astringent and antitussive agent. Lozenges were earlier called
pastilles.
4. Dental cones:
■ These are relatively minor compressed tablet meant for placing them in the
empty socket after tooth extraction. Usually, these tablets contain an
antibacterial, compound which is released slowly. Prevent the growth of
bacteria. These tablets may contain an astringent or coagulant to reduce
bleeding. The base for these types is sodium bicarbonate, sodium chloride or
it may be amines acid. These cones generally get dissolved in 20 to 40 min
time.
 TABLETS ADMINISTERED BY OTHER ROUTE

1.Implantation tablet:
These tablets are placed below the skin or inserted subcutaneously by means of
a minor surgical operation and are slowly absorbed. These must be sterile and
are made by heavy compression and fusion. e.g. Testosterone tablet.

2.Vaginal tablet:
These tablets are meant to dissolve slowly in vaginal cavity. These are ovoid or
pear shaped and are used to release steroids, antibacterial and antiseptics etc
to avoid infections. e.g. Clotrimazole tablet.
 TABLETS USED TO PREPARE SOLUTIONS
1. Effervescent tablet:
These tablets when added in water produce effervescence. So they dissolved rapidly in
water due to the chemical reaction which takes place between alkali bicarbonate and
citric acid or tartaric acid. These tablets are to be protected from atmospheric moisture
during storage (in well closed container). e.g. Disprin tablet (Aspirin)
2. Dispensing tablet:
These are intended to be added to a given volume of water to produce a solution of a given
concentration. The medicaments given are silver proteinate and quaternary ammonium
compounds. These are highly toxic if taken orally and great care must be taken in
packaging and labelling. e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet:
These are compressed tablets which are composed of one or more drugs. These tablets are
dissolved in sterile water and administered parenterally.
4. Tablet triturates:
These are small cylindrical, moulded or compressed tablets which contains a potent
medicament with a diluent. On small scale hand operated whereas for bulk production
automated machines are used. e.g. Enzyme tablet (Digiplex)
Excipients

■ According to the international pharmaceutical excipient council,

Excipient is defined as “Any substance other than active drug or pro-
drug that is included in the manufacturing process or is contained in
finished pharmaceutical dosage forms”.
■ The US pharmacopoeia-National formulary (USPNF) categorizes
excipients according to the functions they perform in the formulations
e.g. Binders, disintegrants etc.
Excipients used in tablet formulation may be classified into two groups:
■ Those that help to impart satisfactory processing and compression
characteristics to the formulation e.g. bulking agents/diluents,
binders, glidants, and lubricants.
■ Those that help to give additional desirable physical characteristics to
the compressed tablets e.g., disintegrants, surface acting agents/
surfactants, colours, flavours and sweetening agents (as in the case
of chewable tablets), polymers or hydrophobic materials (as in the
case of controlled-release tablets).
A typical tablet contains
Tablet excipients
• Filler (or diluent):
A filler, such lactose, is included to increase the size of the tablet. This is necessary as often the
amount of 'active ingredient' is so tiny that the tablet would be too small to handle without it.
• Binder:
A binder, such as starch paste or HPMC, is added to hold the tablet together after it has been
compressed, stopping it from breaking down into its separate ingredients.
• Disintegrant:
Disintegrants, such as starch help the tablet to break down into small fragments, when it is
ingested. This helps the medicine to dissolve and be taken up by the body so that it can act more
quickly.
• Glidant:
The glidants improve the flowability of the tablet granules or powder by reducing the friction
between particles, preventing formation of lumps.
• Antiadherent:
The antiadherents stop the powder from sticking to the equipment as the tablet is being made.
• Lubricant:
Lubricants ensure that the tablet has a smooth surface, they reduce the friction occurs between
the walls of the tablets and the walls of the die cavity when the tablet is ejected.
• Flavor: Flavoring agents help to make the tablet taste better.
• Colorant: Colors are added to help you to recognize your tablet and to make it easier to take
your medicine correctly.
 I-Diluent (filler or bulking agent):

Diluent adds bulk to make the tablet with practical size for compression and to
be easily handled. Tablets weigh normally at least 50 mg, therefore a low dose
of a potent drugs requires addition of a filler to increase the bulk volume of
the powder and hence the size of the tablet.
Examples for potent drugs are:

Corticosteroid drugs such as; Drugs used to replace thyroid hormone

Dexamethasone (0.5 mg/Tablet) Levothroid Tablet (0.05 mg/Tablet)
Requirements for a good filler:
1. Inert, biocompatible, cheap.
2. Non-hygroscopic.
3. Good biopharmaceutical properties. (water soluble or hydrophilic).
4. Good technical properties (compactability )
5. Have an acceptable taste.
  Filler is not necessary if the dose of the drug is high.
 Tablet fillers are mainly carbohydrates and celluloses,
but also some inorganic salts are used.
 One or more diluents may be used in one tablet
preparation.

Most common fillers in tablets:

• Lactose
• Sugar and sugar alcohol (glucose, sucrose, sorbitol and mannitol.
• Cellulose and microcrystalline cellulose.
• Dicalcium phosphate dihydrate.
1- Carbohydrate fillers
Lactose possesses many good filler properties:
- It dissolves readily in water.
- It has pleasant taste (additional sweetening property).
- It is non-hygroscopic and readily dries after wet granulation.
- It shows good compressibility.
- Fairly non-reactive.
- It has high melting point so it does not soften by frictional force of
compression.

Other sugars or sugar alcohols are sucrose, glucose, sorbitol and mannitol have
been used as alternative fillers to lactose, primarily in Lozenges or Chewable
tablets because of their pleasant taste.
Sucrose:
- It provides additional sweetness.
- It is somewhat hygroscopic, tends to turn brown in contact with acidic or
basic substances.
Mannitol:
 It is particularly used as filler for Chewable tablets.
 It has a negative heat of solution and imparts a cooling sensation when sucked
or chewed. Less sensitive to humidity.
 Starches derived from wheat, corn, rice and potato play an important role as
diluent, binder and disintegrant.
 Exists in a number of polymorphic forms.

Sorbitol:
 Exists in a number of polymorphic crystalline forms and amorphous form.
 Widely used in sugar free mints and as a vehicle in chewable tablets.
 good mouth feel.
 Forms a hard compact.
2- Celluloses as fillers

- They are biocompatible, chemically inert and they have good tablet forming
and disintegration properties.
- They are also used as dry binders and disintegrants in tablet manufacture.
- The most common type of cellulose powder is Microcrystalline
cellulose (MCC). Trade names for MCC are Avicel®, Ambicel® & Flocel®.

3- Inorganic salts as fillers:

- An important example is Dicalcium phosphate hydrate; it is water insoluble,

non-hygroscopic, but hydrophilic i.e. easily wetted by water. It is inexpensive
and possesses a high degree of physical and chemical stability.
- Calcium phosphates are highly alkaline and thus be incompatible with drug
sensitive to alkaline conditions.
Selection of diluent

Based on the experience of the manufacturer as well as on the cost of the diluent and
its compatibility with the other tablet ingredients, the proper diluent could be chosen.

1- Calcium salts can not be used as fillers for Tetracycline products because calcium
interferes with the absorption of Tetracycline from GIT.

2- When drug shows low water solubility, it is recommended that water soluble
diluents be used to avoid possible bioavailability problems.

3- The combination of amine bases and salts with Lactose in presence of alkaline
lubricant results in discoloration upon ageing.
II- Binder (adhesive):
Binder is added to drug-filler mixture.
- To promote cohesive compacts during direct compression and ensure the
tablet remaining intact after compression.

- To promote granulation (i.e. as granulator) to ensure free flowing properties

of the particles.

- Binders are used either in a solution or in a dry form depending on other

materials in the formulation & the method of preparation. The binding action
is more effective when the binder is in a solution form than if it was dispersed
in a dry form and moisten with the solvent.

- Materials commonly used as binders include starch, gelatin and sugars as

glucose, lactose. Natural and synthetic gums include acacia, sodium alginate,
methylcellulose and carboxymethylcellulose.
 Examples for binders
Common traditional solution binders are:
- 10-20% aqueous corn
- 25-50% solution of glucose
- Sucrose
- Molasses
- 10-20% solution of gelatin, freshly prepared and used while warm.
- Natural gums (e.g. acacia)
- Ethylcellulose 5% solution (insoluble in water but dissolved in alcohol or as dry
binder), it is widely used as a binder for moisture sensitive materials.
Starch paste
It is prepared by dispersing corn starch in cold purified water to make a 10% w/w
solution, followed by warming in a water bath with continuous stirring until a
translucent paste is formed. Starch paste is not only useful as a binder, but also as a
disintegrant.
More recently used binders today, with improved adhesive properties, are
polymers such as polyvinyl pyrrolidone (PVP) and cellulose derivatives
E.g. methyl cellulose, Carboxymethyl cellulose (CMC) and the most popular
hydroxypropyl methylcellulose (HPMC).

HPMC
HPMC is more dispersible in hot water and more soluble in cold water, hence
in order to obtain smooth gel free from lumps, it is necessary to disperse
HPMC first in hot (almost boiling) water, with agitation, followed by sudden
cooling.

Important examples for dry binders are microcrystalline cellulose (MCC) and
cross-linked PVP.
III- Disintegrant:

Disintegrant is added to tablet formulation:

- To facilitate tablet disintegration (break up) when it contacts fluids in the GIT and
thus promotes rapid drug dissolution.
- Substances routinely included in tablet formulations and in many hard shell
capsule formulation. To promote moisture penetration and dispersion of the dosage
form in dissolution fluids to expose primary drug particles.

Tablet disintegration
Tablet disintegration may be critical to subsequent drug dissolution rate
and to satisfactory bioavailability

Disintegration Deaggregation

in the GIT in the GIT

Intact tablet Granules Primary drug particles

Drug dissolution

Drug in solution in GIT fluids

Absorption Drug in blood

 Mechanisms of action of disintegrants:

All disintegrants are hygroscopic and drow fluids into the matrix
Two main mechanisms:

1- Facilitate water uptake:

They act by facilitating the transport of fluids (GIT) into the tablet pores, so
that the tablet will break into fragments, an obvious example is surface active
agent that makes the drug surface very hydrophilic and thus promote the
wetting of the solid followed by penetration into the pores. (An example is Sod.
Lauryl Sulphate).
Other substances e.g. starch may promote fluid penetration by capillary forces
to suck water into the tablet; the spherical shape of the starch grains increases
the porosity of the tablet, thus promoting the capillary action.
2- Rupture the tablet:
Tablet rupturing can be caused by swelling of the disintegrant particles during
absorption of fluids (in the GIT).

Dry starch Starch after exposure to moisture

 Examples for disintegrants
Common disintegrants include:
- Starch and its derivatives (Sodium Starch Glycolate).
- Cellulose and its derivatives ( MCC, Sod CMC and Croscaramelose)
- Clays (Veegum, bentonite)
- Alginates
- Cation exchange resin

1- The most traditional disintegrant in conventional tablet is Starch (e.g. potato, maize and
corn starch). Its concentration as disintegrant is up to 10%. They swell in water causing tablet
rupturing. Starch in combination with SLS is an effective disintegrant.

2- Super-disintegrants; they can swell dramatically upon exposure to water and thus quickly
and effectively break the tablet. They are included in the formulation at relatively low
concentration 1-5% by weight.
Examples of Super disintegrants are:
■ modified starch (e.g. Sodium Starch Glycolate that swells 7-12 fold in
less than 30 sec).
■ modified cellulose (e.g. Croscaramelose that swells 4-8 fold in less than
10 sec).
■ Cross-linked polyvinylpyrrolidone has been described as having
superiority over corn starch for a number of tablet formulations.
■ Veegum has been shown to be more effective as disintegrator in
sulfathiazole tablets when most of the quantity is added after granulation
and only a small amount before granulation.
How is disintegrant added during the tablet manufacturing?

Extragranular addition Intragranular addition Both Intragranular and

Extragranular addition
- It is more common for -Disintegrant can be mixed - Disintegrant may also be
the disintegrant to be mixed with other ingredients prior added in two steps: A
with the dry granules before to granulation and thus portion is added to drug
tablet compression incorporated into the diluent mixture
granules (Intragranular addition) and
the other portion is mixed
-This procedure will with the dry granules before
contribute to an effective compression (Extragranular
disintegration of the tablet addition). Double
into small fragments disintegration of tablet.
 IV- Glidants, antiadherents and lubricants

They have overlapping functions:

A- Glidants promote the flow of the tablet granules or powder by reducing

friction between particles, e.g. colloidal silica.

B- Antiadherents reduce sticking or adhesion of the tablet granules or powders

to the faces of the punches or the die walls, e.g. Mg stearate, talc and starch.

C- Lubricants reduce the friction occurs between the walls of the tablets and
the walls of the die cavity when the tablet is ejected, e.g. Mg stearate, waxes
and talc.
A.Glidants:
- They are used in the formulation for direct compression.
- They are also added to the granules before tableting to ensure proper flowability of
the tablet mass for high production speed.

Examples for glidants:

-Traditional glidant is Talc powder (1-2% by weight).
-The most common glidant today is colloidal silica (AEROSIL) 0.2% by weight.
-Silica particles are very fine so they adhere to the surfaces of other ingredients
and improve the flow by reducing interparticulate friction. Mg stearate is
mainly used as lubricant but also can be used as glidant (< 1%).
B. Antiadherents:
-Many powders are prone to adhere to the punches ʺsticking" or ʺpickingʺ, which is
affected by the moisture content of the powder.
- Such adherence specially occurred if the tablet punches have markings or symbols.

Examples of antiadherents:
-Mg stearate
-Talc
-Starch
C. Lubricants:

Lubricants are included in all tablet preparations. High friction during tableting can
cause serious problems; inadequate tablet quality (tablet fragmentation during
ejection) and may even stop production.
They improve the rate of flow of the tablet granulation, prevent adhesion of the
tablet material to the surface of the dies and punches, reduce interparticle friction,
and facilitate the ejection of the tablets from the die cavity.
The lubricant should be finely divided by passing through a 100-mesh nylon cloth
onto the granulation (bolting the lubricant).
Examples for lubricants
- Stearic acid and its salts.
- Mg stearate is the most commonly used lubricant owing to its superior lubricant
property (<1% by weight).
- Talc 5% concentration.
- Waxes and hydrogenated vegetable oils.
 Problems due to lubricants

1- They may reduce tablet strength (HOW?) due to their interference with the
bonding between the particles during compression. { bec. they are mainly
hydrophobic and lubricating and thus may counteract the role of the binder}.

2- They may retard tablet disintegration and dissolution such as magnesium

stearate (WHY?) because most lubricants are hydrophobic (counteract the
role of disintegrant). To overcome these waterproofing characteristics,
sodium lauryl sulfate is sometimes included.

3- Alkaline metal stearates (aluminum stearate) and talc are incompatible

with some drugs e.g. aspirin and ascorbic acid. It is preferable to use
hydrogenated vegetable oil or stearic acid with asprin.
 How to avoid this negative effect?
1- Minimum amount of lubricant is to be used.

2- More hydrophilic substances are suggested as alternatives

e.g. surfactants and polyethylene glycol (PEG).

3- Combination hydrophobic and hydrophilic substances may be also useful.

4- Lubricants are added to granules before compression in a finely divided form.

 V- Coloring agents (Colorants):

They are added to the tablet formulation to provide product identification and
acceptable appearance.

- All colorants used in pharmaceuticals must be approved and certified by the FDA.
- Colorants are often accomplished during coating, but can be also included in the
formulation prior to compaction. In the latter case, the colorant can be added as a
soluble dye (wet granulation process) or insoluble lakes (direct compression).
VI- Flavoring agents & sweeteners:

- They are usually limited to chewable tablets or tablets that are intended to dissolve in
mouth, to impart pleasant taste to mask unpleasant taste.

Flavoring agents:
- Water-soluble flavours usually have poor stability. For this reason flavour oils or dry
powders are typically used.
- Oil flavors may be added to tablet granules just before compression (WHY?)
because they are sensitive to moisture and volatilization upon heating (during drying
process).
- Since oils interfere with flowability and compressibility of the granules, minimum
amount of the flavouring agent (0.5% of the granulation) is used to avoid their
negative effect on the tablet characteristics.
Sweetening agents:

- Some sweeteners may come from the diluent (e.g. lactose and mannitol).
- Artificial sweeteners such as Saccharine and Aspartame may be also included.
- Saccharine has an unpleasant after taste.
- Aspartame is unstable in presence of moisture and heat.

Examples of Sweeteners :
• Saccharin is about 400 times sweeter than sucrose but it has bitter after taste,
which can be minimize by the addition of 1% of sod. Chloride .
• Aspartame is about 180 times sweetener than sucrose .
 METHODS OF TABLETS PRODUCTION
There are three main methods by which tablets are manufactured:
(1) wet granulation
(2) dry granulation and
(3) direct compression
Wet granulation
The most widely used process of agglomeration in pharmaceutical industry is wet granulation. Wet
granulation process simply involves wet massing of the powder blend with a granulating liquid, wet
sizing and drying

Important steps involved in the wet Advantages

granulation • Permits mechanical handling of powders without
1. Mixing of the drug(s) and loss of mix quality.
Excipients. • Improves the flow of powders by increasing particle
size and sphericity.
2. Preparation of binder solution.
• Increases and improves the uniformity of powder
3. Mixing of binder solution with density.
powder mixture to form wet mass. • Improves cohesion during and after compaction.
4. Drying of moist granules. • Reduces air entrapment.
• Reduces the level of dust and cross-contamination.
5. Mixing of screened granules with • Allows for the addition of a liquid phase to powders
disintegrant, glidant, and lubricant. (wet process only).
• Makes hydrophobic surfaces hydrophilic.
Material issuance
Drying Dry
& Receiving
screening

Screening of
Flow diagram-wet granulation
Weighing damp mass Lubrication
& mixing

Granulation
Sieving Compression

Preparation of
Dry granulating Final
Blistering
Mixing fluid packing

Limitation of wet granulation

1. The greatest disadvantage of wet granulation is its cost. It is an expensive process because of
labor, time, equipment, energy and space requirements.
2. Loss of material during various stages of processing
3. Stability may be major concern for moisture sensitive or thermolabile drugs.
4. Multiple processing steps add complexity and make validation and control difficult.
5. An inherent limitation of wet granulation is that any incompatibility between formulation
components is aggravated.
Dry granulation

 In dry granulation process the powder mixture is compressed without the use of
heat and solvent. It is the least desirable of all methods of granulation.
 The two basic procedures are to form a compact of material by compression and
then to mill the compact to obtain a granules.
 Two methods are used for dry granulation.
 The more widely used method is slugging, where the powder is recompressed
and the resulting tablet or slug are milled to yield the granules.
 The other method is to precompress the powder with pressure rolls using a
machine such as Chilosonator.
 Roller compaction
 The compaction of powder by means of pressure roll can
also be accomplished by a machine called chilsonator.
 Unlike tablet machine, the chilsonator turns out a compacted
Material issuance Compression Blistering mass in a steady continuous flow.
& receiving
 The powder is fed down between the rollers from the hopper
which contains a spiral auger to feed the powder into the
Lubrication Final
Weighing
& Blending Packing compaction zone.
 Like slugs, the aggregates are screened or milled for
production into granules.
Dry
Sieving
Screening

Use: It is used in the production of directly compressible

excipients, the compaction of drugs and drug formulations. The
Mixing Slugging granulation of inorganic materials, the granulation of dry herbal
material and the production of immediate/sustained release
formulations.

Fig. 9 Flow diagram- Dry granulation Processing steps:

Weighing of raw material-screening-mixing-compression to
slugs-milling-mixing-compression to finished tablets
Advantages:
■ The main advantages of dry granulation or slugging are that it uses less equipments
and space. It eliminates the need for binder solution, heavy mixing equipment and the
costly and time consuming drying step required for wet granulation. Slugging can be
used for advantages in the following situations.
■ For moisture sensitive material.
■ For heat sensitive material.
■ For improved disintegration since powder particles are not bonded together by a
binder.
Disadvantages:
■ It requires a specialized heavy duty tablet press to form slug.
■ It does not permit uniform colour distribution as can be achieved with wet granulation
where the dye can be incorporated into binder liquid.
■ The process tends to create more dust than wet granulation, increasing the potential
contamination.
 Direct compression process
 This method is used when a group of ingredients
can be blended and placed in a tablet press to make Material issuance &
receiving
Final packing

a tablet without any of the ingredients having to be

changed.
Weighing Blistering
 This is not very common because many tablets
have active pharmaceutical ingredients which will
not allow for direct compression due to their Sieving Compression

concentration or the excipients used in formulation

are not conducive to direct compression. Lubrication &
Dry Mixing Blending
 Granulation is the process of collecting particles
together by creating bonds between them. There
are several different methods of granulation.
 The most popular, which is used by over 70% of
formulation in tablet manufacture is wet
granulation. Dry granulation is another method
used to form granules.
Advantages of Direct Compression

1. Cost Effectiveness
2. Stability: Direct compression is more suitable for moisture and heat
sensitive APIs, since it eliminates wetting and drying steps and increases the
stability of active ingredients by reducing detrimental effects.
3. Faster Dissolution
4. Less wears & tears of punches
5. Simplified Validation
Materials are "in process" for a shorter period of time, resulting in less
chance for contamination or cross contamination, and making it easier to
meet the requirement of current good manufacturing practices. Due to fewer
unit operations, the validation and documentation requirements are reduced.
Due to the absence of water in granulation, chance of microbial growth is
minimum in tablets prepared by direct compression.
 Limitations of direct compression
1. Segregation: Direct compression is more prone to segregation due to the difference in density of the API and
excipients.
2. Cost: Directly compressible excipients are the speciality products produced by patented spray drying, fluid bed
drying, roller drying or co-crystallization. Hence, the products are relatively costly than the respective raw
materials.
3. Low dilution potential: Most of the directly compressible materials can accommodate only 30-40 % of the
poorly compressible active ingredients like acetaminophen that means the weight of the final tablet to deliver the
500 mg of acetaminophen, would be more than 1300 mg. The large tablets may create difficulty in swallowing.
4. Re-workability: All the spray-dried directly compressible adjutants show poor rework ability since on
preparation of tablets the original spherical nature of the excipient particles is lost. API that has poor flow
properties and/or low bulk density is difficult to process by direct compression.
5. Lubricant sensitivity: Lubricants have a more adverse effect on the filler, which exhibit almost no fracture or
shear on compression (e.g. starch 1500). The softening effects as well as the hydrophobic effect of alkaline
stearates can be controlled by optimizing the length of blending time to as little as 2-5 min.
6. Variation in functionality: There is a lack of awareness in some situations that the excipient behave differently,
depending upon the vendor quality of the excipients varies so substitution of excipient from one source to that of
another is not possible. Hence, there is a need for greater quality control in purchasing of raw material to assure
batch uniformity.
Thank
You