TableT

Introduction-
• According to USP, Tablet is defined as a compressed solid dosage form
containing medicaments with or without Excipients.
• According to the Indian Pharmacopoeia, Tablets are solid, flat, unit dosage
form, prepared by compressing a mixture of drug and excipients with or
without diluents.

TABLETS

Types of tablets-
a. Tablets ingested orally:
➢ Compressed tablets
➢ Multiple compressed tablets
➢ Enteric coated tablet
➢ Film coated tablets
➢ Chewable tablets
b. Tablets used in oral cavities:
➢ Buccal Tablets
➢ Sublingual Tablets
➢ Lozenges
➢ Dental cones

c. Tablets administered by other routes:

➢ Implantation tablets
➢ Vaginal tablets

d. Tablets used to prepare solutions:

➢ Effervescent tablets

a. Tablets ingested orally-

i. Compressed tablets:-

• These tablets are formed by compression and contain no any special

coating. They are made from powdered, granules materials, alone or
in combination with suitable excipients.
• These tablets contain water soluble drugs which after swallowing
get disintegrated in the stomach and its drug contents are absorbed
in the gastrointestinal tract and distributes in the whole body.
For example- Aspirin, Paracetamol tablets.
 Paracetamol Tablet

ii. Multiple compressed tablets/ Layered tablets-

• These are compressed tablets made by more than one compression
cycle. Such tablets are prepared by compressing additional ta bet
granulation on a previously compressed granulation. The operation
mar be repeated to produce multi layered tablets of two or three
layers.

Multilayered tablets
iii. Enteric coated tablets:
• These are compressed tablet meant for administration by
swallowing and are designed to by- pass the stomach and get
disintegrated in the intestine only.
• These tablets are coated with materials resistant to acidic pH (like
cellulose acetate phthalate, CAP) of the gastric fluid but
disintegrate in the alkaline pH of the intestine.

Enteric coated tablets

iv. Sugar coated tablets:

• These are compressed tablets containing a sugar coating. Such
coatings are done to mask the bitter and unpleasant odour and taste of
the medicament. The sugar coating makes the tablet elegant and it
also safeguard the drug from atmospheric effects.
 Sugar coated tablets
v. Film coated tablets:
• The compressed tablets having of some polymer substance, such as
hydroxy propyl cellulose, hydroxy propyl methyl cellulose and ethyl
cellulose.
• The film coting protects the medicament from atmospheric effects.
Film coated tablets are generally tasteless, having little increase in the
tablet weight and have less elegance than that of sugar coated tablets.

Film coated tablets

vi. Chewable tablets:

• These are the tablets which are required to be broken and chewed in
between the teeth before ingestion. These tablets given to the
children who have difficulty in swallowing and to adults who dislike
swallowing.
Example- Antacid tablets.
 Chewable tablets

b. Tablets used in oral cavity

1) Buccal tablets:
• These tablets are to be placed in the side of the cheek (buccal
pouch) where they dissolve slowly and are absorbed directly in the
buccal cavity without passing into the alimentary canal.
For example- Progesterone tablets
Buccal tablets
 2) Sublingual tablets:
• These tablets are to be placed under the tongue where they dissolve
or disintegrate quickly and absorbed directly without passing into
GIT.
For example- Tablets of nitroglycerin, isoproterenol hydrochloride.

Sublingual tablets

3) Lozenges Tablets:
❖ These tablets are designed to exert a local effect in the mouth or
throat. These tablets are commonly used to treat sore throat to
control coughing in common cold. They may contain local
anaesthetics , antiseptics, antibacterial agents and astringents.
❖ These are prepared by compression at high pressure by the moulding
process and generally contain a sweetening agent, flavouring agent
and a substance which roduces a cooling effect.
Vicks lozenges, Strepsils.
 4) Dental cones:
▪ These are compressed tablets meant for placement in the empty
sockets after tooth extraction. They prevent the multiplication of
bacteria in the socket.
▪ These tablets contain an excipient like lactose, sodium bicarbonate
and sodium chloride. These cones generally dissolved in 20 to 40
minutes time.

Dental cones

c. Tablets administered by other routes

1) Implantation Tablets:
➢ These tablets placed under the skin or inserted subcutaneously by
means of minor surgical operation and are slowly absorbed. The
implants must be sterile and should be packed individually in sterile
condition. Implants are mainly used for the administration of hormones
such as testosterone steroids for contraception .
 2) Vaginal tablets:
▪ These tablets are meant to dissolved slowly in the vaginal cavity.
The tablets are typically ovoid or pear shaped for the ease of
insertion. These tablets are used to release steroids or antimicrobial
agents.

d. Tablets used to prepare solutions

a) Effervescent tablets:
• These tablets along with the active medicament contain ingredients
like sodium bicarbonate, citric acid ant tartaric acid which react in
the presence of water liberating carbon dioxide and producing
effervescence leading to disintegration of tablets, thus fastens
solution formation and increase the palpability.
Ex- Histac (Ranitidine)
 Effervescent tablets

Advantages of tablet dosage form over other oral drug delivery

systems
From patients stand point :
• They are easy to carry, easy to swallow and they are attractive in
appearance.
• Unpleasant taste can be masked by sugar coating and they do not
require any measurement of dose.
• Some of the tablets are divided into halves and quarters by making
lines during manufacturing to facilitate breakage whenever a
fractional dose is required.

From the standpoint of manufacturer:

• An accurate amount of medicament, even if very small, can be
incorporated.
• Since they are generally produced on large scale, therefore, their cost of
production is very low, hence economical.

Disadvantages of tablet dosage form

• Difficult to swallow in case of children and unconscious patients.
 • Bitter tasting drugs, drugs with an objectionable odour or drugs that are
sensitive to oxygen may require encapsulation or coating. In such cases,
capsule may offer the best and lowest cost.

Tablet Ingredients / Excipients-

1 Diluent/Filler
2 Binder and adhesive
3. Disintegrants
4. Lubricants and glidants
5. Colouring agents
6.Flavouring agents
7. Sweetening agents

Function of excipients-
➢ Impart weight, accuracy, & volume.
➢ Improve solubility.
➢ Increase stability
➢ Enhance bioavailability
➢ Modifying drug release
➢ Assist product identification
➢ Increase patient acceptability
➢ Facilitate dosage form design

1. Diluents
 Diluents are filler used to make required bulk of tablet when the drug dosage
itself is inadequate to produce the bulk.

Characteristics of an ideal diluents

• They must be nontoxic and acceptable to the regulatory agencies in all
countries where the product is to be marketed.
• They should be commercially available in an acceptable grade in all
countries where the product is to manufactured.
• They must be cheap compared to the active ingredients and must be
physiologically inert.
• They must be chemically stable.
• They must be colour- compatible.
• They must be no negative effects on the bioavailability of the drug in the
product.

Commonly used tablet diluents-

I. Lactose- anhydrous and spray dried lactose
II. Directly compressed starch- Sta Rx 1500
III. Mannitol and Sorbitol
IV. Dextrose

2. Binders and Adhesive

Agents used to impart cohesive qualities to the powdered material are referred
to as binders or granulators.

Objective of incorporating binders

 • They impart a cohesiveness to the tablet formulation which ensure the tablet
remaining intact after compression.
• They improve the free flowing qualities by the formation of granules of
desired size and hardness.

Characteristics of binder
Method-1
• Binders are used in dry form in the powder and then moistened with a
solvent to form wet lumps.

Method- 2
• Binders are often added in solution form. It requires lower concentration of
binder.
• By method- 1 the binder is not as effective in reaching and wetting each of
the particles within the mass of the powder. Each of the particle in a powder
blend has a coating of absorbed air on its surface, and it is this film of air
which must be penetrate before the powder can be wetted by the binder
solution.

Method- 3
• In direct compression method MCC, microcrystalline dextrose, amylose and
PVP are used- those have good flow property and cohesiveness as well.
• It has been postulated that MCC is a special from of cellulose fibril in
which individual crystallites are held together largely by hydrogen bonding.
The disintegration of tablets containing the cellulose occurs by breaking
intercrystallite bonds by the disintegrating medium.

3. Disintegrants
 A disintegrant is a substance to a mixture of substances, added to tablet to
facilitate its breakup or disintegration after administration in the GIT. The
active ingredients must be released from the tablet matrix as efficiently as
possible to allow for its rapid dissolution.

Disintegrants can be classified chemically as: starches, clays, celluloses,

gums and cross-linked polymers.

Starch
• Corn starch, potato starch.
• For their disintegrating effect starches are added to the powder
blends in dry state.
Mode of action:
• Starch has a great affinity for water and swells when moistened, thus
facilitating the rupture of the tablet matrix.
• Others have suggested that the spherical shape of the starch grains
increase the porosity of the tablet, thus promoting capillary action.
• Normally 5% w/w is suggested and for rapid disintegration 10-15% w/w
may be taken.

4. Lubricant and Glidants

Objectives:
• Prevents adhesion of the tablet material to the surface of dies and
punches.
• Reduce inter-particular friction, improve the rate of flow of tablet
granulation.
• Facilitate ejection of the tablets from the die cavity.

Lubricants are intended to prevent adhesion of the tablet materials to the

surface of dies and punches, reduce inter particle friction and may improve the
rate of flow of the tablet granulation.
Example- Stearic acid, Magnesium stearate, Talc, PEG, surfactants.
Glidants are intended to promote flow of granules or powder material by reducing
the friction between the particles.
Example- Corn Starch- 5-10%conc., talc5% conc.

5. Colouring agent

Objectives of using colours that

1. It makes the tablet more esthetic in appearance.
2. Colour help the manufacturer to identify the product during its
preparation. Colorants are obtained in two forms dyes and lakes.
Dyes are dissolved in the binding solution prior to the granulating process.
However, during drying their colour may migrate to the surface and may produce
mottling of the tablet. So another approach is to adsorb the dye on starch or
calcium sulfate from its aqueous solution; the resultant powder is dried and blende
with other ingredients.
Colour lake dyes are adsorbed onto a hydrous oxide of a heavy
metal resulting in an insoluble form of dye.

6. Flavours and Sweeteners

Flavours are usually limited to chewable tablets or other tablets intended to
dissolve in the mouth. Flavour oils are added to tablet granulation in solvents,
are dispersed on clays and other adsorbents or emulsified in aqueous
granulating agents.
The use sweeteners is primarily limited to chewable tablets. Ex- Sugar
Mannitol- 72% as sweet as sugar, cooling & mouth filling effect.
Saccharin- Artificial sweetener, 500 times sweeter than sucrose.
Manufacturing of tablets
Manufacture of tablets involves certain well defined steps:
➢ Pulverization and mixing.
➢ Granulation
➢ Compression
➢ Coating (if required)

Pulverization and mixing-

• In this step the different solid/powder ingredients are reduced to the same
particle size since particles of different sizes will segregate while mixing.
• Various equipments like Cutter mill, Hammer mill, Roller mill and Fluid
energy mill is required to reduce the large lumps.

Granulation Technology-
Granulation: It is the process in which primary powder particles are made to
adhere to form large multi-particle entities.
Range of size:0.2mm to 4mm.
Objectives:-
➢ To enhance the flow of powder.
➢ To produce dust free formulations and produce uniform mixtures.
➢ To improve compaction characteristics.
➢ To eliminate poor content uniformity of mixture.
➢ To avoid powder segregation. As Segregation may result in weight
variation.
Percolation Segregation:- Air void
Trajectory Segregation:- Kinetic energy
There are two methods of granulation:
1. Wet granulation.
2. Dry granulation.
Wet Granulation-
Granulation is a critical process for transforming powders into uniform, free-
flowing granules, which are then compressed into tablets.
Tablet Preparation by Wet Granulation:-
1. Mixing: Combine the active pharmaceutical ingredient with
excipients.
2. Granulation: Add a granulating liquid to the powder mix to form a
wet mass.
3. Screening: Pass the wet mass through a screen to produce
granules.
4. Drying: Dry the granules using a fluid bed dryer or tray dryer.
5. Milling: Mill the dry granules to a uniform size.
6. Blending: Blend the granules with lubricants and disintegrants.
7. Compression: Compress the blend into tablet press.

APIs + Excipients

Mixing/Blending

Granulation (wet
granulation)

Drying of wet granules

Spray fluidized bed
granulation

Milling

Tableting

Coating
Dry granulation:-
Dry granulation is the process of forming particles-i.e., granulates or granules
from dry powder or powder blend without adding liquid to aid in the process.

Types of dry granulation

Typically, dry granulation can be done in two ways: either by roller compaction or
by slugging.

Slugging process in dry granulation

Slugging is the another form of dry granulation. It is also known as double
compression . This cost-effective dry granulation method also works well for raw
materials that are sensitive to heat and moisture.

The powdered solids are mixed and then pressed into flat-faced large-sized tablets
(slugs) on a conventional tablet press. The process is performed without using heat
or solvents. Then, the slugs are milled into granules.
Dry granulation steps:-
Steps of the slugging process
❖ A powder blend is fed into a tablet press.
❖ The blend is compressed into extra large tablets or slugs using flat-faced
punches.
❖ The slugs are subjected to screening both before and after the slugging
procedure.
❖ The slugs are then broken down into the desired particle size by a hammer
mill or an oscillating granulator.
❖ The milled particles are screened to form the final granules.

What machines are used in dry granulation process?

Dry granulators are the machines used to perform the dry granulation process.
There are many different types of dry granulators out there including oscillating
granulators and roller compaction machine.
Advantages of dry granulation process
❖ The process doesnot use any liquid or solvent, suitable for moisture-sensitive
APIs or excipients.
❖ This method does not involve the drying stage, so it is ideal for processing
heat-sensitive materials.
❖ The method makes compacted and milled powder easier to compress during
tableting.
❖ The process can adjust the compaction force and milling process
parameters. This helps control the granule hardness and particle size.

Disadvantages of dry granulation

❖ The major disadvantage of the method is that a higher % of fines or non-
compacted particles. This can lower the quality of the final product.
 ❖ The process is not suitable for all material. The powder blend to be
granulated must have the desired compressibility to form a compact mass
under pressure.

Tablet compression
It can reduce the volume by apply pressure, particle in die are re-arrange, resulting
a closer packing structure and reduce space and at certain lode reduce space and
increase inter-particulate friction will prevent farther interparticulate friction.

Basic Component of Compression Machine

Head-Contain upper punches,dies,lower punches.
Body- Contain operating machinaries.
Hopper- Holding feeding granules.
Dies- Define size, shape of tablet.
Punches- For compression with in dies.
Cam tracks- Guiding the movement of punches.
Feed frame- Guiding the granules from hopper to dies.
Upper turret- Holds the upper punches.
Lower turret- Hold the lower punches.
Die table- Contain the dies.
Single station – stamping press.
Multi-station – Rotary press
Tablet Processing Problems and its remedies-
An ideal tablet should be free from any visual defect or functional defect. With the
development of technology, the production process had become more simplified
and mechanized.
But now the tablet punching machines are all mechanized, the mechanical feeding
of feed from the hopper into the die, electronic monitoring of the press, but tablet
process problem still persist.
An industrial pharmacist usually encounters number of problems during
manufacturing. Majority of visual defects are due to inadequate quality or
inadequate moisture in the granules ready for compression or due to faulty
machine setting.

The Imperfection known as: ‘VISUAL DEFECTS’ are either related to

Imperfection in any one or more of the following factors:
1. Formulation design
2. Tableting process
3. Machine
Capping and Lamination
Capping is the partial or complete separation of the top or bottom crowns of a
tablet from the main body of the tablet.
Lamination is the separation of tablet into two or more distinct layer. Usually
these problems are apparent immediately after compression, or even hour or days
later.

Detection: Subjecting tablets to the friability test is the quickest way to reveal such
problems.

Reasons and Remedies

Reason:

• Entrapment of excess air in the granules during compression. If the granules

are light and fluffy this type of problems are encountered frequently.
• New set of punches and dies are very tightly fitted; i.e. the clearance is very
negligible hence air cannot come out.
• Granules should not be completely dried. If over dried or under dried then
capping may take place.
• Tooling set used for longer period of time will form claw-shaped curve on tip
of the punch or wear ring in die in compression area-this form capping.
Remedies:

• Increase the density of granules by adding more binder or

changing the solvent of binder.
• Punch diameter should be reduced by 0.005’’
• Moisture content should be kept within 1-4%.
• Punches and dies should be changed.

Picking and Sticking

• Picking: When some portion of the surface of the tablet is removed- it is
termed as picking.
• Sticking: Sticking refers to tablet material adhering to the die wall. Serious
sticking at ejection cause chipping.

Causes and remedies of picking

Cause: When punch tips have engraving or embossing, usually of letters B,A,O
are difficult to manufacture cleanly. These may produce picking.

Remedies:
1. Lettering should be designed as large as possible, particularly
on punches of small diameter.
2. Plating of the punch faces with chromium produces smooth, non-
adherent face.
3. Colloidal Silica is added as polishing agent that makes the
punch faces smooth; so that material does not cling to them.

Causes and Remedies of Sticking

Causes: Excessive moisture may be responsible for sticking.
 During compression heat is generated and low m.p. lubricants e.g. stearic acid
may produce sticking.
Remedies:
Further drying of the granulation is then required.
Low melting point lubricant are replaced with high melting point lubricant.

Mottling
Mottling is an unequal distribution of colour on a tablet, with light or dark patches
in an otherwise uniform surface.

Causes: Migration of water soluble dyes to the surface while drying.

Remedies:
• Change the solvent system and change the binder system.
• Reduce the drying temperature
• Grind to a smaller particle size.
• Use lakes instead of water-soluble dyes.

Quality control test for tablets-

• General appearance - Size, shape, and thickness, this is important to
facilitate packaging and to decide which tablet compressing machine to use.
• Organoleptic properties: Which include colour, odour and taste of tablets.
• Weight uniformity and Content uniformity: The tablet should contain the
correct dose of the drug.
• Dissolution test: Drug should be released from tablet in a controlled and
reproducible way.
 • Weight variation, thickness & diameter: The appearance of tablet should be
elegant & its weight, size & appearance should be consistent.
• Hardness & friability: The tablet should show sufficient mechanical
strength to withstand fracture & erosion during manufacture & handling.

These factors must be controlled during production and verified after production,
hence called In-process control.

Weight Variation:-
This test is based on the fact that, if the weight variation is within the limits then it
can be said that the amount of medicament will uniform considerably. Conversely,
if the weight variation is not in limits then it can be concluded that the active
medicament will uniform considerably.
Sources of weight variation
Weight variation is solely dependent on the poor flow property of granules and
filling of die cavity. Poor flow properties arise from:
a) Improper lubrication
b) Size of granules
c) Adjustment of lower punch
Weight variation test
The U.S.P weight variation test is run by weighing 20 tablets individually,
calculating the average weight, and comparing the individual tablet weights to the
average. The tablets meet the USP test if ‘not more than 2 tablets are outside the
percentage limit and if no tablet differ by more than 2 times the percentage limit.’

Content uniformity test:-

Weight variation test is applicable when the amount of medicament in the tablet
is high.
• In potent drug the medicament is less in amount in comparison to the other
excipients. The weight variation may meet the pharmacopoeial limitation but
this will not ensure the correct variation of potency. Hence, in this case the
weight variation test is followed by content uniformity test.
• In this test 30 tablets are randomly selected for sample, and at least 10 of
them are assayed individually according to the official assay method.
• 9 of the 10 tablets must have potency within +15% or -15% of the labelled
drug content. Only 1 tablet may be within +25% or -25%.
• If this condition is not met then the tablets remaining from the 30 must be
assayed individually and none may fall outside +15% or -15% of the
labelled content.

Disintegration Test of tablets

❖ The time a tablet takes to disintegrate is the disintegration time.
❖ To test the disintegration time one tablet is placed in each tube, and the
basket rack assembly is positioned in a 1-litre beaker of water, simulated
gastric fluid or simulated intestinal fluid, at 37 degree Celsius +or – 2
degree celsius, such that the tablet remains 2.5 cm from the bottom of the
beaker.
 ❖ A standard motor moves the basket out and down through a distance of 5 to
6 cm at a frequency of 25 to 32cpm

Dissolution test:-
• Disintegration test simply identifies the time required for the tablet to break
up under the condition of the test but it does not ensure the drug release in
the bulk of the fluid.
• Rate of dissolution is directly related to the efficacy of the drug. Rate of
dissolution is a good index for comparing the bioavailability of two tablet
products of the same drug.

Apparatus-1 (Basket):-
➢ In general, a single tablet is placed in a small wire mesh basket and
immersed in the dissolution medium contained in a 1000ml flask at 37
Degree Celsius. Generally it is rotated at 50 rpm unless otherwise specified.

Apparatus-2 (Paddle):-
 ➢ The same equipment is used. Instead of a paddle is introduced as the stirring
element. The tablet is allowed to sink at the bottom of the flask before
stirring.
➢ Limit: A value of t90% (i.e 90% drug release) within 30 minutes is often
considered satisfactory and is an excellent goal since a common dissolution
tolerance in the USP/NF is not less than 75% dissolved in 45 minutes.

Tablet Hardness:-
The resistance of the tablet to chipping, abrasion or breakage under conditions of
storage, transportation and handling before usage depends on its hardness.
Method:
A tablet is taken between the 2nd and 3rd finger and pressing it with the thumb as
fulcrum. If the tablet breaks with a ‘sharp snap', yet, it does not break when it falls
on the floor- is said to possess proper hardness.

Instruments used:
a) Monsanto harness tester
b) Strong Cobb Hardness Tester- Manual mode.

Hardness of a tablet:
The hardness at which the tablet crushes is the harness of the tablet.
• Unit of hardness : Kg/sq.in. or lb/sq.in
• Limit: Generally maximum 5 kg/sq.in. hardness is required.

Friability:-
Tablet hardness is not an absolute indicator of strength since some formulation,
when compressed into very hard tablets may produce chipping, capping and
lamination problems. Therefore, another measure of tablet strength i.e. friability is
often measured, i.e. the friability.

Instrument: Roche Friabilator

Objective of friability test:

This apparatus is designed to evaluate the ability of the tablet to withstand
abrasion, in handling, packaging and shipping operation.
Method: 20 tablets, previously weighed are taken in the plastic chamber of the
laboratory friability tester. In the plastic chamber the tablets are subjected to
abrasion and shock by rotating the plastic chamber at 25 rpm for 4 mins (i.e. total
100 revolution). The tablets are dedusted and reweighed.
Limit: For conventional compressed tablet the weight loss should be within 0.5 to
1.0%.