TABLET DOSAGE FORMS

TABLET:

It is a solid dosage form each containing a unit dose of one or more medicament/s.
Tablets are solid, flat or biconvex discs prepared by compressing a drug or a mixture
of drugs with or without suitable excipients.
Tablets may be swallowed whole or being chewed. Some are dissolved or dispersed in
water before administration. Some are put in oral cavity, where the active ingredient is
liberated at a predetermined rate. Implants or passeries may also be presented in form
of tablet.
Tablet may vary in shape and differ greatly in size and weight depending on the
amount of medicinal substance and the intended mode of administration.

Advantages and disadvantages of tablet as a dosage form:

The advantages are listed below:
I.Large scale manufacturing is feasible in comparison to other dosage forms. Therefore,
economy can be achieved.
II.Accuracy of dose is maintained since tablet is a solid unit dosage form.
III. Tailor made release profile can be achieved.
IV. Longer expiry period and minimum microbial spillage
owing to lower moisture content.
V. As tablet is not a sterile dosage form, stringent environmental conditions are not required
in the tablet department.
VI. Ease of packaging (blister or strip) and easy handling over liquid dosage form.
VII. Easy to transport in bulk. Emergency supply supplies can be carried by patients.
VIII.Organoleptic properties (taste, appearance and odour) are best improved by coating of
tablet.
IX. Product identification is easy and markings done with the help of grooved punches and
printing with edible ink.
X. Different types of tablets are available like buccal, floating, colon targeting, effervescent,
dispersible, soluble, and chewable, etc.
XI. In composition to parenterals dosage form, a doctor or a nurse is not required for
administration. I.e. self administration is possible.
1

XII. In comparison to capsules, tablets are more tamperproof.

The disadvantages are listed below:
I.It is difficult to convert a high dose poorly compressible API into a tablet of suitable size for
human use.
II.Difficult to formulate a drug with poor wettability, slow dissolution into a tablet.
III. Slow onset of action as compared to parenterals, liquid orals and capsules.
IV. The amount of liquid drug (e.g. Vitamin E, Simethicone) that can be trapped into a tablet
is very less.
V. Difficult to swallow for kids, terminally ill and geriatric patients.
VI. Patients undergoing radiotherapy cannot swallow tablet.

Various Types Of Tablets

1.1

ORAL
TABLETS FOR
INGESTION

1.1.1 Standard compressed tablets

1.1.2 Multiple compressed tablets
I. Compression coated tablet
II. Layered tablet
III. Inlay tablet
1.1.3 Modified Release tablet
1.1.4 Delayed action tablet
1.1.5 Targeted tablet
I. Floating tablet
II. Colon targeting tablet
1.1.6 Chewable tablet

1.2

1.1.7 Dispersible tablet

1.2.1 Lozenges and troches

TABLETS
USED IN THE ORAL
CAVITY
1.2.2 Sublingual tablet
1.2.3 Buccal tablet

1.2.4 Dental cones

1.3

1.2.5 Mouth dissolved tablet

1.3.1 Vaginal tablet

TABLETS
ADMINISTERED BY
OTHER ROUTES 1.3.2 Implants
1.4
TABLETS
1.4.1 Effervescent tablet
USED TO PREPARE
SOLUTION
1.4.2 Hypodermic tablet
1.4.3 Soluble tablet

1.1 ORAL TABLETS FOR INGESTION

These tablets are meant to be swallowed intact along with a sufficient quantity of potable
water. Exception is chewable tablet. Over 90% of the tablets manufactured today are ingested
orally..
1.1.1 Standard compressed tablets
These are the standard uncoated tablets made by either direct compression or wet granulation
or dry granulation or double compaction.

Standard Compressed Tablet

They may be used for local action in gastro-intestinal tract or systemic action
e.g., antacids and adsorbents.
1.1.2 Multiple compressed tablets
The tablets in this category are prepared for two reasons: to separate physically or chemically
incompatible ingredients and to produce repeat action/ prolonged action tablet.
There are three categories under this class:
I.Multi Layered tablets

two to three component system.

II.Compression coated tablets

tablet within a tablet.

III.Inlay tablet

coat partially surrounding the core.

The layered tablet is preferred over compression coated tablet as the surface contact is less
and the production is simple and more rapid.
I. Multilayered tablets
When two or more active pharmaceutical ingredients are needed to be administered
simultaneously and they are incompatible, the best option for the formulation pharmacist
would be to formulate multilayered tablet. It consists of several different granulations that are
compressed to form a single tablet composed of two or more layers and usually each layer is
of different colour to produce a distinctive looking tablet. Each layer is fed from separate feed
frame with individual weight control..
For example,
admixture containing Phenylephedrin HCL and Ascorbic Acid with Paracetamol.
Paracetamol + phenylephedrine Hydrochloride

one layer

Paracetamol + ascorbic acid

another layer.

Multilayered Tablet

II. Compression coated tablets

This type of tablet has two parts, internal core and surrounding coat. The core is small porous
tablet and prepared on one turret. For preparing final tablet, a bigger die cavity in another
turret is used in which first the coat material is filled to half and then core tablet is
mechanically transferred, again the remaining space is filled with coat material and finally
compression force is applied.

Compression Coated Tablet

III. Inlay tablet

A type of layered tablet in which instead the core tablet being completely surrounded by
coating, top surface is completely exposed. While preparation, only the bottom of the die
cavity is filled with coating material and core is placed upon it. When compression force is
applied, some coating material is displaced to form the sides and compress the whole tablet.
4

It has some advantages over compression coated tablets:

i)Less coating material is required.
ii)Core is visible, so coreless tablets can be easily detected.
iii)Reduction in coating forms a thinner tablet and thus freedom from capping of top coating.

Inlay Tablets

1.1.3 Modified Release tablets

The main aim behind formulation of this dosage form is to release the medicament slowly for
long time duration after administration of a single tablet.

Graphical Comparison Of Blood Concentration V/S Time

A widespread use of this type of tablet is seen in present scenario, as well as many
researchers have concentrated their attention in this direction. This is mainly because of
improvement in patients compliance as the dosage frequency is reduced, patient can take an
undisturbed sleep at night, its also beneficial for psychiatric patients who forget to take their
tablets regularly and the dose related side effects and toxicities are reduced.

1.1.4 Delayed action tablets

Enteric coated tablet is such an example of delayed action tablet.
This formulation is preferred when...
i)The API irritates gastric mucosa

e.g.,

aspirin or strong electrolytes

ii)Drugs that produce nausea and vomiting.

iii)API is sensitive to low pH

e.g.,

erythromycin

iv)When its necessary to release the drug undiluted. e.g.,

intestinal antibacterial, antiseptic

agents, intestinal vermifuge, etc.
5

The commonly used coating agents are:

Cellulose acetate phthalate,Hydroxy methyl propyl phthalate,polyvinyl
acetatephthalate,Eudragit, etc.
This dosage form is intended to hydrate and begin to dissolve in duodenum (pH 4 to 6) or in
small intestine where pH increases to 7 to 8.

1.1.5 Targeted tablets

When we need to release the API at a specific site in the elementary tract, targeted drug
delivery is a preferred option.
we have two types of tablet:

I. Gastro retentive Tablet

This type of dosage form is to be opted when APIrelease is desired in stomach (Antacids,
APIs used against H.pylori infection)or site of absorption is either stomach or upper part of
small intestine.

Floating Tablet
To retain the drug for longer time period in stomach,following approaches can be used:
i) Low density tablet (effervescent or non effervescent)
ii) Tablets that can expand in gastric environment (swelling or by unfolding) and thus
increasing the size so that it cannot cross the pyloric sphincter.
iii) Using mucoadhesive polymers that stick to mucosa of stomach and provide slow drug
release.
Supine position is to be avoided and also high level of fluid is necessary or if the swelling
formulation leaves stomach before it swells its ineffective.
Drugs like Diazepam, Levodopa, Benserazide, and Ciprofloxacin are successfully marketed
in this formulation.

II. Colonic tablets

When the aim is to deliver the drug into colon without dilution in other regions of
gastrointestinal tract or the drug has poor absorption in stomach or small intestine, colonic
6

drug delivery is an answer of choice. The pH in this region varies from 6.4 - 7 and presence
of microbial flora plays as important role in drug release especially in this region.Various
mechanisms are adopted for drug release in this area are coating with pH sensitive polymer
e.g., EudragitS100, Eudragit L100, biodegradable polymer like polymers which are
sensitive to colonic bacteria, bioadhesive polymers which selectively sticks to colonic
mucosa e.g., polycarbophils or polyethans, redox sensitive polymers that respond to redox
potential in colon which expresses the total metabolic and bacterial action.

1.1.6 Chewable tablets

The patients who have difficulty in swallowing tablets whole or for children who have not yet
learnt to swallow a tablet, chewable tablet serves as an attractive alternative. The added
advantage of this medication is that it can be taken at any time or when water is not available.
Mannitol is normally used as a base due to low hygroscopy and more importantly, it gives
pleasant, cooling sensation. Antacid tablets are invariably prepared as chewable to obtain
quick ingestion relief as well as the antacid dose is too large to swallow and the activity is
related to particle size.

1.1.7 Dispersible tablet

These tablets disintegrate either rapidly in water, to form a stabilized suspension, or disperse
instantaneously in the mouth to be swallowed without the aid of water. So, its preferred for
pediatric patients who cannot swallow a solid dosage form and the API is unstable if
formulated in liquid formulation. Also helpful for patients having prolonged illness who are
prone to nauseatic sensations if they have to swallow a tablet. The added advantage of this
formulation is faster onset of action as compared to standard compressed tablet. The
properties of the water dispersible tablet, such as porosity, hardness, disintegration time and
increase in viscosity after dispersion are necessary to investigate during manufacturing which
decides the product performance.
The common examples of API formulated in this dosage form are analgesics e.g., aspirin,
ibuprofen, etc.

1.2 Tablets used in the oral cavity

The tablets under this group are aimed release API in oral cavity or to provide local action in
this region. The tablets under this category avoids first-pass metabolism, decomposition in
gastric environment, nauseatic sensations and gives rapid onset of action. The tablets
formulated for this region are designed to fit in proper region of oral cavity.

1.2.1

Lozenges and troches

The tablet is a flat faced at least about 18mm in diameter and meant to suck and dissolves in
the mouth. The compressed tablet is called troches and the tablets produced by fusion or
candy molding process are called lozenges. Flavours and sweeteners are added to make
tablets palatable. The tablet generally contains sucrose or lactose and gelatin solution to
impart smooth taste. Lozenges for local action in mouth/ throat are: antiseptics, antibiotics,
demulcents, antitussive agents or astringents.
7

1.2.2 Sublingual tablets

They are to be placed under the tongue and produce immediate systemic effect by enabling
the drug absorbed directly through mucosal lining of the mouth beneath the tongue.

Sublingual Tablets
For example, Glyceryl trinitrate (vasodilator) and Isoprinosine sulphate (bronchodilator).

1.2.3 Buccal tablets

Completeness of drug absorption is desired but fast drug absorption is not intended. The
tablets are designed not to disintegrate. They are flat elliptical or capsule shaped tablets as it
can be easily held between gum and cheek. Its placed near the opening of parotid duct to
provide the medium to dissolve the tablet.

Since this tablet is to be kept for 30-60 minutes in oral cavity, care should be taken to see that
all the ingredients are finely divided to avoid gritty or irritating sensation. This tablet is most
often used when replacement hormonal therapy is to be administered. Antifungal drugs are
preferred to be administered by this route.
e.g., Miconazole under preclinical trial still not in market.

1.2.4 Dental cones

These tables are designed to be loosely packed in the empty socket remaining following a
tooth extraction.

Dental Cones
Main purpose behind the use of this tablet is either to prevent multiplication of bacteria in the
socket by employing a slow releasing antibacterial compound or to reduce bleeding by an
astringent or coagulant containing tablet. Its formulated to dissolve or erode slowly in
presence of a small volume of serum or fluid over 20-40 minutes period.
8

1.2.5 Mouth Dissolved tablets/ Rapidly Dissolving tablets

.These kinds of tablets are preferred when fast action or relief is desired. Most commonly
used drugs under this formulation are the agents active against Migraine. The tablets are
designed to disintegrate as well as dissolve within one minute or some within 10 seconds of
oral administration in limited quantity of saliva. They liquefy on tongue and patient swallows
the liquid, without the need of water.. Urea, urethane, ammonium carbonate, ammonium
bicarbonate, hexamethylene, benzoic acid, naphthalene and camphor are commonly used for
sublimation processing as they they volatize rapidly. After removal by sublimation, these
inert volatile substances leave the matrices with a high porosity.These dosage forms have
become a delivery system of choice for most patients as they provide comfort for
administration throughout the day. Pharmaceutical companies, on the other hand, benefit
from value addition in terms of product life-cycle management in todays market.

1.3 TABLETS ADMINISTERED BY OTHER ROUTES

These tablets are administered by other route except for the oral cavity and so the drugs are
avoided from passing through gastro intestinal tract. These tablets may be inserted into other
body cavities or directly placed below the skin to be absorbed into systemic circulation from
the site of application.

1.3.1 Vaginal tablets

This tablet undergoes slow dissolution and drug release in vaginal cavity of women. The
shape is kept ovoid or pear shaped to facilitate retention in vagina. The tablet should be made
compatible with plastic tube inserters which are designed to place the tablet in the upper
region of vaginal tract. These tablets generally release antibacterial, antiseptics or astringents
to treat vaginal infections or release steroids for systemic absorption.

1.3.2 Implants
These tablets are inserted into subcutaneous tissue by surgical procedures where they are very
slowly absorbed over a period of a month or a year. A special injector with a hollow needle
and plunger is used to administer the rod shaped tablet for other shapes, surgery is required.
The tablets may be pellet, cylindrical or rosette shaped with diameter not more than 8mm.
Mainly, these tablets are prepared to deliver growth hormones to food producing animals and
ear is the preferred site for administration of the drug.

1.4 Tablets used to prepare solution

The tablets under this category are required to be dissolved first in water or other solvents
before administration or application. This solution may be for ingestion or parenteral
application or for topical use depending upon type of medicament used.
1.4.1 Effervescent tablets
The oral dosage forms are the most popular way of taking medication despite having some
disadvantages like slow absorption and thus onset of action is prolong. This can be overcome
by administrating the drug in liquid from but, many APIs have limited level of stability in
9

liquid form. So, effervescent tablets acts as an alternative dosage form. The tablet is added
into a glass of water just before administration and the drug solution or dispersion is to be
drunk immediately. The tablet is quickly broken apart by internal liberation of CO2 in water
due to interaction between tartaric acid and citric acid with alkali metal carbonates or
bicarbonates in presence of water.

Effervescent Tablets
Due to liberation in CO2 gas, the dissolution of API in water as well as taste masking effect is
enhanced. The advantages of effervescent tablets compared with other oral dosage forms
includes an opportunity for formulator to improve taste, a more gentle action on patients
stomach and marketing aspects.The manufacturing shall be done under controlled climatic
condition to avoid effervescent reaction The most commonly used effervescent tablet today is
aspirin tablet.
1.4.2 Hypodermic tablets
These tablets contain one or more readily water soluble ingredients and are intended to be
added in water for injection of sterile water to form a clear solution which is to be injected
parenterally. They were widely used by rural physician due to its portability. One bottle of
sterile water was carried by the doctor to prepare many types of injectables. It can be used for
medicaments whose stability in water is very poor.
1.4.3 Soluble tablets
Tablets are pre-formed solids of uniform shape and dimensions, usually circular, with either
flat or convex faces, the distance between faces being less than the diameter. Water soluble
tablets are intended for application after dissolution in water and contain an active ingredient
should be totally soluble in water at used concentrations.

Soluble Tablets

PHARMACEUTICAL EXCIPIENTS FOR TABLET FORMULATION

Pharmaceutical excipient means any component other than the pharmacologically active drug
which are included in the manufacturing process or are contained in a finished
pharmaceutical product dosage form.
10

While selecting excipients for any formulation following things should be considered
wherever possible: keep the excipients to a minimum in number minimize the quantity of
each excipients and multifunctional excipients may be given preference over unifunctional
excipients.
Fewer ingredients in the formulation are better for the following reasons:
Excipients are not completely inert. Even commonly used excipients that are deemed
to be pharmaceutically inactive and nontoxic may cause adverse reactions;
Less ingredient variability to influence process and product consistency;

Better economic efficiency in product manufacturing;

Less probability of chemical or physical interaction between API and excipients and
among excipients.

Excipients play a crucial role in design of the delivery system, determining its quality and
performance.
Excipients though usually regarded as nontoxic there are examples of known excipient
induced toxicities which include renal failure and death from diethylene glycol, osmotic
diarrhoea caused by ingested mannitol, hypersensitivity reactions from lanolin and
cardiotoxicity induced by propylene glycol.
Excipients may also be important for keeping the drug from being released too early in the
assimilation process in places where it could damage tender tissue and create gastric
discomfort or stomach upset.
Excipient Grades.
Many excipients for pharmaceutical use are available in different grades. These grades are
differentiated frequently by means of physical and chemical characteristics.
The reason for grades is to change the performance characteristics of excipients.
Excipients are chosen in tablet formulation to perform a variety of functions like
1. For providing essential manufacturing technology functions (binders, glidants,
lubricants may be added),
2. For enhancing patient acceptance (flavors, colourants may be added),
3. For providing aid in product identification (colourants may be added),
4. For Optimizing or modifying drug release (disintegrants, hydrophilic polymers,
wetting agents, biodegradable polymers may be added),
5. For enhancing stability (antioxidant, UV absorbers may be added)

EXCIPIENT WITH THEIR FUNCTIONS IN TABLET FORMULATION

EXCIPIENT
Diluents or

FUNCTION
Diluents make the required bulk of the tablet when the drug dosage itself is
11

Fillers

inadequate to produce tablets of adequate weight and size.

Binders or
Granulating
agents or
Adhesives

Binders add cohesiveness to powders, thus providing the necessary bonding

to form granules, which under compaction form a cohesive mass or a
compact which is referred to as a tablet.

Disintegrants

Disintegrant is added to facilitate a breakup or disintegration of the tablet

when placed in an aqueous environment.
Antifrictional Agents

Lubricants

Lubricants are intended to reduce the friction during tablet formation in a die
and also during ejection from die cavity.

Antiadherents

Antiadherents reduce sticking or adhesion of any of the tablet granulation or

powder to the faces of the punches or to the die wall.

Glidants

Glidants promote the flow of tablet granulation or powder mixture from

hopper to the die cavity by reducing friction between the particles.
MISCELLANEOUS

Wetting agents

Wetting agents are added to tablet formulation to aid water uptake during
disintegration and assist drug dissolution.

Dissolution
retardants

Dissolution retardants as the name suggest, retards the dissolution of active

pharmaceutical ingredient(s).

Dissolution
enhancers

Dissolution enhancers as the name suggest, enhance the dissolution rate of

active pharmaceutical ingredient(s).

Adsorbents

Adsorbents are capable of retaining large quantities of liquids without

becoming wet; this property of absorbent allows many oils, fluid extracts
and eutectic melts to be incorporated into tablets.

Buffers

Buffers are added to provide suitable micro environmental pH to get

improved stability and / or bioavailability.

Antioxidants

Antioxidants are added to maintain product stability, they act by being

preferentially oxidized and gradually consumed over shelf life of the
product.

Chelating agents are added to protect against autoxidation; they act by

Chelating agents forming complexes with the heavy metal ions which are often required to
initiate oxidative reactions.
Preservatives

Preservatives are added to tablet formulation in order to prevent the growth

of micro-organisms.

Colours

Colours are added to tablet formulation for following purposes: to disguise

off colour drugs, product identification and for production of more elegant
product.

Flavours

Flavours are added to tablet formulation in order to make them palatable

enough in case of chewable tablet by improving the taste.

Sweeteners

Sweeteners are added to tablet formulation to improve the taste of chewable

tablets.

1.Diluents (Fillers)
12

In order to facilitate tablet handling during manufacture and to achieve targeted content
uniformity, the tablet size should be kept above 2-3 mm and weight of tablet above 50 mg.
Usually the range of diluent may vary from 5-80%.
Diluents are also synonymously known as fillers. Diluents are often added to tablet
formulations for secondary reasons like to provide better tablet properties such as:
i)To provide improved cohesion
ii)To allow direct compression manufacturing
iii)To enhance flow
iv)To adjust weight of tablet as per die capacity

Classification of diluents
Tablet diluents or fillers can be divided into following categories:
i)Organic materials - Carbohydrate and modified carbohydrates.
Examples:
Powdered cellulose, Microcrystalline cellulose (MCC), Starch,
Starch 1500 (Pregelatinized Starch),Lactose, Sucrose,
Mannitol, Sorbitol
ii)Inorganic materials Calcium phosphates and others.
iii)Co-processed Diluents
Tablet diluent or filler may also be classified on the basis of their solubility in water as
soluble and insoluble.
INSOLUBLE TABLET DILUENTS
Starch

SOLUBLE TABLET DILUENTS

Lactose

Powdered
cellulose

Sucrose
Mannitol

Microcrystalline
cellulose

Sorbitol,
etc.

Calcium phosphates, etc.

Selection of diluent should be done after considering properties of diluent such as:
13

Compactibility, flowability, solubility, disintegration qualities, hygroscopicity, lubricity

and stability.
Co-processed diluents:
Co-processing means combining two or more materials by an appropriate process. The
products so formed are physically modified in such a special way that they do not loose their
chemical structure and stability. Now a days direct compression technique has been one of
the well-accepted methods of tablet manufacture.

2.Binders
Binder is one of an important excipient to be added in tablet formulation. In simpler words,
binders or adhesives are the substances that promote cohesiveness. It is utilized for
converting powder into granules through a process known as Granulation. Granulation is the
unit operation by which small powdery particles are agglomerated into larger entities called
granules.

Classification of Binders
Sugaras

Natural Binders

Synthetic/Semisybthetic Polymer

Sucrose

Acacia

Methyl Cellulose

Liquid glucose

Tragacanth

Ethyl Cellulose

Gelatin

Hydroxy Propyl Methyl Cellulose ( HPMC)

Starch Paste

Hydroxy Propyl Cellulose

Pregelatinized Starch

Sodium Carboxy Methyl Cellulose

Alginic Acid

Polyvinyl Pyrrolidone (PVP)

Cellulose

Polyethylene Glycol (PEG)

Polyvinyl Alcohols
Polymethacrylates

Characteristics of Commonly Used Binder

14

BINDER
Starch Paste

SPECIFIED
CONCENTRATION
5-25%w/w

COMMENTS
- Freshly prepared starch paste is used as a binder.

- It is starch that have been processed chemically

and/or mechanically to ruptureall or part of the
granules in the presence of water and subsequently
dried.
- It contains 5% free amylose, 15% free amylopectin
Pregelatinized
5-10%w/w
and 80% unmodified starch.
Starch
(Direct Compression) - used as tablet binder, diluent, disintegrant and flow
aid.
(PGS)
5-75%w/w
- They enhance both flow and compressibility and
[Partially and
(Wet Granulation )
can be used as binders in Direct Compression as
Fully PGS
well as Wet Granulation.
- High purity PGS allow simplified processing as they
swell in cold water and therefore reduce time/costs
compared with traditional starch paste
preparation.
Hydroxypropyl
Methyl
2-5%w/w
Cellulose
(HPMC)

Polyvinyl
Pyrrolidone
(PVP)

0.5-5%w/w

Polyethylene
Glycol (PEG) 10-15%w/w
6000

- Comparable to Methyl Cellulose.

- Used as a binder in either wet or dry granulation
processes.

- Soluble in both water and alcohol.

- Used in wet granulation process.
- added to powder blends in the dry form and
granulated in situ by the addition of water, alcohol or
hydroalcoholic solution.
- Binder for chewable tablets.
- The drug release is not altered on storage.

Used as a meltable binder.

Anhydrous granulating agent where water or
alcohol cannot be used .
It may prolong disintegration time when
concentration is 5% or higher
- It improves the plasticity of other binders.

3.Disintegrants

15

.Disintegrants, an important excipient of the tablet formulation, are always added to tablet to
induce breakup of tablet when it comes in contact with aqueous fluid and this process of
desegregation of constituent particles before the drug dissolution occurs, is known as
disintegration process and excipients which induce this process are known as disintegrants.
The objectives behind addition of disintegrants are to increase surface area of the tablet
fragments and to overcome cohesive forces that keep particles together in a tablet.
.List Of Disintegrants
DISINTEGRANTS

CONCENTRATION
IN GRANULES (%W/W)

SPECIAL COMMENTS

Starch USP

5-20

Higher amount is required,

poorly compressible

Starch 1500

5-15

Avicel(PH 101,
PH 102)

10-20

Lubricant properties and

directly compressible

Solka floc

5-15

Purified wood cellulose

Alginic acid
Na alginate

1-5
2.5-10

Acts by swelling
Acts by swelling

Explotab

2-8

Sodium starch glycolate,

superdisintegrant.

Polyplasdone(XL)
Amberlite (IPR 88)

0.5-5
0.5-5

Crosslinked PVP
Ion exchange resin

Methyl cellulose, Na CMC,

HPMC

5-10

AC-Di-Sol

1-3

Direct compression

Carbon dioxide

2-4
_

Wet granulation
Created insitu in effervescent
tablet

Superdisintegrants
As days passes, demand for faster disintegrating formulation is increased. So, pharmacist
needs to formulate disintegrants i.e. Superdisintegrants which are effective at low
concentration and have greater disintegrating efficiency and they are more effective
intragranularly. But have one drawback that it is hygroscopic therefore not used with
moisture sensitive drugs.
List Of Superdisintegrants
SUPERDISINTEGRANTS

EXAMPLE OF

MECHANISM OF SPECIAL
ACTION
COMMENT
16

Crosscarmellose

Ac-Di-Sol

Crosslinked
cellulose

-Swells 4-8 folds in -Swells in two

< 10 seconds.
dimensions.
-Swelling and
wicking both.

-Direct compression
or granulation

Nymce ZSX
Primellose
-Starch free

Solutab

Vivasol
Crosspovidone

Crosslinked PVP

Crosspovidon M
Kollidon
Polyplasdone
Sodium starch glycolate
Explotab
Primogel
Alginic acid NF
Satialgine

Soy polysaccharides
Emcosoy

-Swells very little

and returns to
original size after
compression but
act by capillary
action

-Water insoluble and

spongy in nature so
get porous tablet

Crosslinked starch -Swells 7-12 folds in -Swells in three

<30
dimensions and high
seconds
level serve as
sustain release
matrix
Crosslinked alginic -Rapid swelling in -Promote
acid
aqueous medium or disintegration in
wicking action
both dry
or wet granulation
Natural super
disintegrant

-Does not contain

any starch or sugar.
Used in nutritional
products.

Effect of surfactants on DISINTEGRATION:

Surfactant

Remarks
17

Sodium lauryl sulfate

Good-various drugs

Polysorbate 20
Polysorbate 40 & 60
Polysorbate 80
Tweens
Poly ethylene glycol

Poor - various drugs

Good
Poor
Good
Poor
Poor

(Good decrease in disintegration time, Poor increase in disintegration time)

Antifriction Agents :
Lubricants,Antiadherents and Glidants
Lubricants
Lubricants work by reducing friction by interposing an intermediate layer between the tablet
constituents and the die wall during compression and ejection and also between particle
during compression.
Classification of Lubricants
Lubricant are classified (based on their water solubility) into two groups :
1. water insoluble
2. water soluble
Insoluble Lubricants
Stearates(Magnesium Stearate,
Calcium Stearate, Sodium
stearate)
Talc
Sterotex

Concentration
0.25-1
1-2

Comments
Reduce tablet strength and prolong
disintegration
Insoluble but not hydrophobic,
moderately effective.

0.25-1

Waxes

1-5

Stearowet

1-5

Glyceryl behapate (Compritol

888)

1-5

Both lubricant and binder

Liquid paraffin

Up to 5

Dispersion problem, inferior to stearates

List Of Soluble Lubricants

18

Water Soluble Lubricants

Concentration range (%w/w)

Boric acid

Sodium benzoate

Sodium oleate

Sodium acetate

Sodium lauryl sulfate (SLS)

1-5

Magnesium lauryl sulfate (MLS)

1-2

Antiadherents
Some material have strong adhesive properties towards the metal of punches and dies or the
tablet formulation containing excessive moisture which has tendency to result in picking and
sticking problem. Therefore, antiadherents or anti-sticking agents prevent adhesion of the
tablet surface to the die walls and the punches. Talc, magnesium stearate and corn starch have
excellent antiadherent properties. Vegan had suggested that silicon oil can be used as
antiadherent.
List Of Antiadherents
Antiadherent

Concentration
Range
(%w/w)

Comments

Talc

1-5

Lubricant with excellent antiadherents properties

Corn starch

3-10

Lubricant with excellent antiadherents properties

Colloidal silica
DL-Leucine

0.1-0.5
3-10

Does not give satisfactory results due to small surface

area. Cab-O-Sil and Syloid
Water soluble lubricant; excellent antiadherents
properties

Sodium Lauryl Sulfate

less than 1

Antiadherents with water soluble lubricant

Stearates

less than 1

Antiadherents with water insoluble lubricant

Glidants
Glidants are added to the formulation to improve the flow properties of the material which is
to be fed into the die cavity and aid in particle rearrangement within the die during the early
stages of compression. If the flow properties are extremely poor then glidants are ineffective
and consideration of force free mechanisms may be necessary. The effect of glidants on the
flow of the granules depends on the shape and size of the particle of the glidant and the the
granule.
Examples:
The commonly used glidants are talcum, starch, colloidal silica silicates, stearates calcium
phosphate, etc.
19

Wetting Agents
Wetting Agents in tablet formulation aid water uptake and thereby enhancing disintegration
and assisting in drug dissolution.
Incorporation of anionic surfactant like Sodium Lauryl Sulphate (SLS) is known to enhance
the dissolution.It has been established that SLS improves permeation of drug through
biological membrane since it destroys the path through which drug has to pass and thus
minimizing the path length for the drug to travel.
Wetting agents are mainly added when hydrophobic drug is to be formulated into tablet.
Examples:
SLS, Sodium diisobutyl sulfosuccinate are used as wetting agent in tablet formulation.

Dissolution Retardants
Dissolution Retardants are incorporated into tablet formulation only when controlled release
of drug is required.
Examples:
Waxy materials like stearic acid and their esters can be used as dissolution retardants.

Dissolution Enhancers
They are the agents that alter the molecular forces between ingredients to enhance the
dissolution of solute in the solvent.
Examples:Fructose, Povidone, Surfactants are used as dissolution enhancer.

Adsorbents
Adsorbents are the agents that can retain large quantities of liquids. Therefore liquids like
Vitamin E can be incorporated into tablets by addition of adsorbents ..
Examples:
Most commonly used adsorbents in pharmaceuticals are anhydrous calcium phosphate,
starch, magnesium carbonate, bentonite, kaolin, magnesium silicate, magnesium oxide and
silicon dioxide

Buffers
Buffers are added to maintain a required pH since a change in pH may cause significant
alteration in stability.
Examples:
20

Most commonly used buffering agent in tablet formulation includes sodium bicarbonate,
calcium carbonate, and sodium citrate.

Antioxidants
Antioxidants are added in tablet formulation to protect drug from undergoing oxidation.
Antioxidants undergo oxidation in place of drug or they block the oxidation reaction or they
act as synergists to other antioxidants. Chelators may also act as antioxidant.
Examples:
Most commonly used antioxidants include ascorbic acid and their esters , alpha-tocopherol ,
ethylene diamine tetra acetic acid , sodium metabisulfite , sodium bisulfite , Butylated
Hydroxy Toluene (BHT) , Butylated Hydroxy Anisole (BHA) , citric acid , and tartaric acid .

Chelating Agents
Chelating agents tend to form complexes with trace amount of heavy metal ions inactivating
their catalytic activity in the oxidation of medicaments.
Examples:
Ethylenediamine tetracetic acid and its salts, Dihydroxy Ethyl Glycine, Citric Acid and
Tartaric Acid are most commonly used chelators.

Preservatives
Preservatives may be a part of tablet formulation in order to prevent the growth of
microorganisms in tablet formulation.
Examples:
Parabens like methyl, propyl, benzyl, butyl p-hydroxy benzoate are used as preservatives.

Colourants
Colourants neither contribute to therapeutic activity nor do they improve product
bioavailability or stability but are incorporated into tablets for purposes like to facilitate
identification of similar looking products with in a product line to avoid mix ups, to facilitate
identification of products of similar appearance that exist in the lines of different
manufacturers, to overcome colour change on aging, disguising of off-colour drugs, for brand
image in the market, to enhance the aesthetic appearance of the product to have better patient
acceptance.
Some Commonly Used Pharmaceutical Colourants (Synthetic)
FD &
C COLOUR

COMMON
NAME
21

Red 3
Red 40
Yellow 5
Yellow 6
Blue 1
Blue 2
Green 3

Erythrosine
Allura red AC
Tartrazine
Sunset Yellow
Brilliant Blue
Indigotine
Fast Green

Flavours
Flavors are commonly used to improve the taste of chewable tablets as well as mouth
dissolved tablets.
Flavors are incorporated either as solids (spray dried flavors) or oils or aqueous (water
soluble) flavors.

Sweeteners
Sweeteners are added primarily to chewable tablets.
Some Of The Sweeteners Used In Tablet Formulation
NATURAL
SWEETENERS

ARTIFICIAL
SWEETENERS

Mannitol

Saccharin

Lactose

Cyclamate

Sucrose

Aspartame

GRANULATION TECHNOLOGY ON LARGE SCALE BY VARIOUS

TECHNIQUES

22

Physics of compression :

A tablet is formed by reducing tile volume of a set of autonomous particles until they are
consolidated into a solid body
Tablet consolidation occurs when the punches and die go between two compression rollers
23

The complete tablet manufacturing cycle occurs in four steps:

(i) the die is filled,
(ii ) the fill weight is adjusted,
(iii) the tablet is compacted. and
(iv) the tablet ejected from the die .
From a material point of view, a compaction process is normally described by a series of
sequential phases

Compression :
Tableting procedure
Filling
Compression
Ejection

Compression process:
Filling

By gravitational flow of powder from hopper via the die table into die. The die
is closed at its lower end by the lower punch.

Compression
The upper punch descends and enters the die and the powder is compressed
until a tablet is formed.

During the compression phase, the lower punch can be stationary or can move
upwards in the die.

After maximum applied force is reached, the upper punch leaves the powder
i.e. the decompressed phase.

During this phase, the lower punch rises until its tip reaches the level of the
top of the die. The tablet is subsequently removed from the die and die table
by a pushing device.

Ejection

Common stages occurring during compression

Stage 1: Top punch is withdrawn from the die by the upper cam. Bottom punch is low in the
die so powder falls in through the hole and fills the die

24

Stage 2: Bottom punch moves up to adjust the powder weight-it raises and expels some
powder
Stage 3: Top punch is driven into the die by upper cam. Bottom punch is raised by lower
cam. Both punch heads pass between heavy rollers to compress the powder
Stage 4: Top punch is withdraw by the upper cam. Lower punch is pushed up and expels the
tablet. Tablet is removed from the die surface by surface plate
Stage 5: Return to stage 1

Procedure for compression

Granulation stored in hopper-

Transferred to feed frame Which having several compartments.

Spread granule into the die Pull down cam guides the lower punch.

Allowing dies to overfill Punches pass over a weight control cam.

It reduce fill in die to desired amount

Swipe off blade remove excess granulation.

The lower punches travel over the lower compression roll while simultaneously the
upper punches ride beneath the upper compression roll
25

The upper punches enter a fixed distance into the dies, while the lower punches are
raised to squeeze and compact the granulation within the dies

After the moment of compression, the upper punches are withdrawn as they follow
the upper punch raising cam

The lower punches ride up the cam which brings the tablets flush with or slightly
above the surface of the dies

At the same time, the lower punches re-enter the pull down cam and the cycle is
repeated. The tablets strike a sweep off blade affixed to the front of the feed frme and
slide down a chute into a receptacle

TABLET DEFECTS : THE CAUSE AND THE REMEDY

MOTTLING
Unequal distribution of colour on the tablet surface with light and dark areas standing out in
an otherwise uniform coloured surface
Cause :
Variation in the colours of ingredients (drug and other additives)
Drugs with degradation nature and have different coloured degraded products
Migration of dye to the surface of granulation during drying. At high temperature dyes are
easily migrate to surface and spread to upper surface.
Uneven distribution of colored adhesive gel solutions resulting in precipitation
Remedy:
By using bright coloring agent that will mask all the color variations
of the ingredients
Proper drying by reducing the drying temperature
Colored adhesive gel solutions must be added when they are hot too much cooler powder
mixtures to avoid precipitation
It is better to incorporate fine powder adhesives like acacia and tragacanth into product
before adding the granulating fluid
By changing the solvent system or binder system
Grinding to small particle size
CAPPING and LAMINATING
CAPPING :
Capping Continuously high speed of tablet machine and high degree of compression setting
makes tablet to separate main surface into individual surface. Avoid defective punches and
dies. High temperature adjustment also favor capping. Distance between upper and lower
punches will entrap air is bone factor for capping. Fine particles were susceptible than coarse
particles will affect ideality of tablets. Capping minimized by keeping the feed material with
cohesive nature.
LAMINATION :
26

Lamination It is major problem among of all defects. Occur upon storage period, or soon
after compression. Air entrapment between layers of tablet. Low levels of binding agent. It
minimized by improving lubricant concentration. Change the method of granulation. By
direct compression technique it is prevented to some extent. Use always dry material (feed).
Causes

Remedy

Airentrapmentinthetabletamonggranulesor Byprecompression,Reducingfinalcompression,
among
Minimizing
particles
tabletingrate
Deformationalpropertiesofformulationduring
Increasingstressrelaxationtime
andaftercompression
Improper/Deepconcavepunches

Overdriedgranules(Duetolackofcohesion)

Bettertouseflatpunches

Bymaintainingmoisturelevelsusing
hygroscopicmaterials
likeMC(MethylCellulose),Sorbitol,PEG
4000(Polyethyleneglycol)etc.

Impropertooling:
Concaveedgesofpunchesturning Propertooling:
Checkingofpunchesandreplacing
clawshaped
them
Greaterradiusofcurvatureofpunch
Propercheckingandreplacingthem
face

Diesdevelopingawearringshape

Improperadjustmentofsweepoff
blade

Lessriseoflowerpunchduring
ejectionoftable

Poorcompressibilityobservedduringdirect
compressiontechnique

Turningthedieoversothat
compressionoccursinan
unwornareaabovering

Propersettingofsweepoffblade&
lowerpunchrise

Relativecompressibilityistobemaintained

PICKING
Adherence of the tablet material from the surface of a tablet by a punch
Causes:
Because of engraving or embossing or debossing on the punch tips like small enclosed areas
in the letters like A, B, D, O, Q etc
Remedy:
Lettering should be designed as large as possible, even the tablet size can be increased by
reformulation
Colloidal silica can be added as polishing agent to formula
Using additional binder to increase cohesiveness of granules and thereby causing decreased
adherence
Plating of punch faces with a chromium material to obtain smooth face which is non27

adherent
Avoid wet granules.
STICKING
Sticking always occurs in low melting point substances, and moisture supports this defects,
lower the speed up of upper and lower punch leads to weight variation of tablets. It produces
rough and chipping surface tablets. It develops material on both punches. Lack of drying is
basis of this one.
Causes:
Presence of low melting point substances in the formula ex. Stearic acid, PEG
(Polyethylene glycol) etc , which gets soften due to compressive heat
Excessive moisture in the granules
Remedy:
Partial or complete substitution of low melting point components with high melting point
materials in the formula
Proper drying of the granules to remove excessive moisture
Selection of Binding agent is essential to solve sticking.
Ideal selection of lubricant in desired proportion will minimized this problem.
WEIGHT VARIATION (Granule size and size distribution)
Causes:
Improper blending of granules
Lack of sufficient of lubricant .
Abnormal uniform mixing of all excipients.
Improper tool setting of machine. Hi-speed running of machine.
improper glidant selection.
Improper drying making tablet with different weight.
Proportion of small to large granules influence the die filling capacity and thereby results in
weight variation of tablets
If large granules are used to fill small die cavities, even a small difference in granules
results in high percent weight variation of tablets
Remedies: Uniform size distribution (Narrow) and smaller granular size is preferable
POOR FLOW
Causes:
Improper design of hopper
Poor flow of granules
Bridging/arching and rat-holing of granules at the bottom of the hopper
Segregation or stratification of particles due to use of flow promoting
devices like vibrators
Surges of excessive flow above the hopper
Remedies:
Flow can be improved by using glidants like talc, colloidal silica etc.
28

 By proper design of the hopper

By using flow enhancing devices like vibrators
By preparing uniform sized and shaped granules
POOR MIXING
Causes:
Improper mixing of ingredients like glidants and lubricants useful for
proper flow and punching
Insufficient or inadequate time of mixing
Remedy:
Proper mixing by maintaining adequate time and using suitable mixer
PUNCH VARIATION
Cause:
Unequal lengths of lower punches which results in variations of granular
volume filled in die
Remedy:
Proper tooling by using good and uniform sized punches
HARDNESS VARIATION
Causes:
Due to weight variation in granules filled in die
Space between lower and upper punches
Remedy:
Proper tooling of machine
DOUBLE IMPRESSION
Cause:
Uncontrolled movement of punches with engravings on them
Remedy:
Using anti-turning devices

TABLET COATING:
Coating is performed for the following reasons:
1. Providing controlled, continuous release or reduce the frequency of drug dosing
2. Maintaining physical or chemical drug integrity
3. Enhancing product acceptance and appearance
4. Protects the tablet (or the capsule contents) from stomach acids
29

5. Protects the stomach lining from aggressive drugs such as enteric coated aspirin
6. Provides a delayed release of the medication
7.Maintains shape of the tablet.

ASPECTS OF TABLET COATING

I. Therapy
i) Avoid irritation of oesophagus and stomach
ii) Avoid bad taste
iii) Avoid inactivation of drug in the stomach
iv) Improve drug effectiveness
v) Prolong dosing interval
vi) Improve dosing interval
vii) Improve patient compliance
II. Technology
i) Reduce influence of moisture
ii) Avoid dust formation
iii) Reduce influence of atmosphere
iv) Improve drug stability
v) Prolong shelve life
III. Marketing
i) Avoid bad taste
ii) Improve product identity
iii) Improve appearance and acceptability

Basic principle of tablet coating

Basic principles involve

30

i) Insulation which influences the release pattern as little as possible and does not markedly
change the appearance.
ii) Modified release with specific requirement and release mechanism adapted to body
function in the digestive tract
iii) Colour coating which provides insulation or is combined with modified release coating.

TYPE OF TABLET COATING PROCESS

Sugar coating
Compressed tablets may be coated with coloured or uncoloured sugar layer. The coating is
water soluble and quickly dissolves after swallowing. The sugarcoat protects the enclosed
drug from the environment and provides a barrier to objectionable taste or order. The sugar
coat also enhances the appearance of the compressed tablet and permit imprinting
manufacturings information. Sugar coating provides a combination of insulation, taste
masking, smoothing the tablet core, colouring and modified release. The disadvantages of
sugar coating are the time and expertise required in the coating process and thus increases
size, weight and shipping costs.
Sugar coating process involves five separate operations:
I. Sealing/Water proofing: provides a moisture barrier and harden the tablet surface.
II. Subcoating: causes a rapid buildup to round off the tablet edges.
III. Grossing/Smoothing: smoothes out the subcoated surface and increases the tablet size to
predetermine dimension.
IV. Colouring: gives the tablet its colour and finished size.
V. Polishing: produces the characteristics gloss.

Enteric coating
This type of coating is used to protect tablet core from disintegration in the acid environment
of the stomach for one or more of the following reasons:
i) To prevent degradation of acid sensitive API
ii) To prevent irritation of stomach by certain drugs like sodium salicylate
iii) Delivery of API into intestine
iv) To provide a delayed release component for repeat action tablet
Several kinds of enteric layer systems are now available
31

One layer system - The coating formulation is applied in one homogeneous layer,
which can be whites-opaque or coloured. Benefit is only one application needed.
Two layer system - To prepare enteric tablets of high quality and pleasing appearance the
enteric formulation is applied first, followed by coloured
film. Both layers can be of enteric polymer or only the basic layer contains enteric polymer
while top layer is fast disintegrating & water-soluble polymer

Controlled release coating

Polymers like modified acrylates, water insoluble cellulose (ethyl cellulose), etc. used for
control release coating.

Specialized coating
Compressed coating
This type of coating requires a specialization tablet machine. Compression coating is not
widely used but it has advantages in some cases in which the tablet core cannot tolerate
organic solvent or water and yet needs to be coated for taste masking or to provide delayed or
enteric properties to the finished product and also to avoid incompatibility by separating
incompatible ingredients.
Electrostatic coating
Electrostatic coating is an efficient method of applying coating to conductive substrates. A
strong electrostatic charge is applied to the substrate. The coating material containing
conductive ionic species of opposite charge is sprayed onto the charged substrate. Complete
and uniform coating of corners and adaptability of this method to such relatively
nonconductive substrate as pharmaceutical is limited.
Dip coating
Coating is applied to the tablet cores by dipping them into the coating liquid. The wet tablets
are dried in a conventional manner in coating pan. Alternative dipping and drying steps may
be repeated several times to obtain the desired coating. This process lacks the speed,
versatility, and reliability of spray-coating techniques.
Vacuum film coating
Vacuum film coating is a new coating procedure that employs a specially designed baffled
pan. The pan is hot water jacketed, and it can be sealed to achieve a vacuum system. The
tablets are placed in the sealed pan, and the air in the pan is displaced by nitrogen before the
desired vacuum level is obtained. The coating solution is then applied with airless spray
system..

Equipments
Three general types of equipments are available
32

1. Standard coating pan

e.g.,

Pellegrin pan system

Immersion sword system
Immersion tube system

2. Perforated pan system

e.g.,

Accela cota system

Hicoater system
Glattcoater system
Driacoated system

3. Fluidized bed coater

EVALUATION OF TABLET
Before a tablet is released out into the market it has to pass a few quality checks,
which is mandatory. Evaluation of tablet includes the assessment of tablets physical, chemical
and biological properties. To studies them the following test are formulated
1) GENERAL APPEARANCE:

General appearance is the physical appearance of the tablet it has two aspects
to address
First one is the patient compliance, if the tablet is appearance is legible and
good, it improves the patient compliance.
The second one Is for the manufacturer, it helps him in trouble free
manufacturing if there is tablet to tablet, batch to batch and lot to lto
uniformity of tablet.
General appearance would include a number of aspects like, size, shape, odor,
taste, texture, legibility, identifying marks.

2) SIZE AND SHAPE:

Different shapes and sizes of tablet are available in the market they are
manufactured in order to differentiate them based on their purpose of use and
quantity of active ingredient, and the age group of the patient who is going to
be administered with the drug.
Heart shape tablet signify that they are for the cardiac problems, small toy
shape, tablet are manufactured in order to attract children etc.
The shape and size of a tablet would vary based on tooling used in the tablet
manufacturing.
The prime consideration here would be the crown size, because if the
concavity is very high it many lead to capping, or chipping problem.
33

The crown size is measured by using micrometer, and sliding caliper scale is
used to measure the size of 5 to 10 tablets at a time.

3) UNIQUE IDENTIFICATION MARK:

Pharmaceutical manufacturers in order to differentiate their product from the

other manufacturers emboss a special marking g on the tablet. The marking
can be an embossing, engraving or printing.
Apart from the company marking there can be imprints which include
product code, product name, product potenct,
But care must be taken that the letters that are embossed on the tablet are
properly printed without double impression.

4) ORGANOLEPTIC PROPERTIES:

For rapid identification of the tablet and consumer acceptance the tablet are
given a specific colour, the colour of the tablet will enable the manufacturer
form differentiating the tablet lot.
The uniformity of the colour is important parameter here, the tablet should be
free form mottling.
The colour uniformity and gloss of the tablet is evaluated by using
reflectance spectrophotometer, tristimulus colorimetric measurement,
microreflectance photometer.
The odour of the tablet indicate the stability of the tablet, for example, the
smell of acetic acid in aspirin tablet indicates that the tablet is degraded
The taste of the tablet is also an important factor, every company has a taste
panel which enalise the taste of the tablet, machines are yet to be discovered
which can provide the report of the taste.

TABLET THICKNESS
Tablet thickness is determined by
1) the diameter of die.
2) the amount of fill permitted to enter the die.
3) the compatability of the fill material.
4) the force or pressure applied during compression.
The tableting press affects not only tablet thickness but also tablet hardness.
Tablet thickness may be measured by hand gauge or automated equipment.

34

Tablet hardness: Force required to break a tablet in diametric compression test.

1) The greater the pressure applied, the harder the tablets.
2) The hardness required by different tablets
a) Lozenges and buccal tablets: hard (dissolve slowly)
b) The tablets for immediate drug release: soft (dissolve slightly faster)
3) Hardness is function of Die fill
a) At constant compression force, hardness increases with increase in die fill
b) At constant die fill Hardness increases & thickness decreases with Increase in compression
force.
MEASUREMENT
a) Subjective: Breaking the tablet between 2nd & 3rd fingers with thumb as fulcrum: sharp
snap deemed to have acceptable strength.
b) Special dedicated hardness testers (Monsanto, Pfizer, etc)
Generally used Hardness testers are:
Monsanto Tester
Strong-Cobb Tester
Pfizer Tester
Erweka Tester
Schleuniger Tester
Hardness for compressed tablet is 5 to 8 kg

Pfizer tester

Erweka tester

Monsanto tester

Schleunigertester

TABLET FRIABILITY
Friability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic
chamber that revolves at 25 rpm, dropping the tablets through a distance of six inches in the
friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress
35

tablet that lose less than 0.5 to 1.0 % of the tablet weigh are consider acceptable. If capping is
observed on friability testing, the tablets should not be considered for commercial use.

Roche friabilator

6) WEIGHT VARIATION:

Weight variation test is performed to check that the manufactured tablets have
an uniform weight.
As per USP twenty tablets are weighed individually and an compendia weight
is taken, the average weight is obtained by dividing the compendia weight by
20, now the average weight is compared to the individual weight of the tablet,
For a tablet to pass the test not more than 2 tablets should lie out of the
specified percentage and if no tablet differs by more than two times the
percentage limit.

Sno Average weight

Maximum percentage difference

allowed

130 or less

10

130-324

7.5

More than 324

7.CONTENT UNIFORMITY TEST

Applies to potent drug of low dose
Method:
36

Tablet sample----- 30
A)10 tablets Assayed individually------- at least 9 should be 85-115%, one tablet may 75-125
%------ pass test
B)20 tablets Assayed---- All should be 85-115% then pass test
If any deviation whole batch fails in test
Content non uniformity is due to
- Non uniform distribution of drugs in powder or granules -Segregation
-weight variation (only gives approx hint of content non uniformity)
8.TABLET DISINTEGRATION TEST
The significance of tablet disintegration : Prerequisite for dissolution and bioavailability
It is in-process and finished product QC tool
Testing apparatus: USP disintegrating test apparatus:
-6 glass tubes 3 inch long dia=2.15mm
-open at top, #10 screen at bottom
-1 L beaker, kept at 37 + 2 C
-28-32 cycles per second
If the tablets are floating use disc having 1gm wt

Procedure :
6 Tablets placed in each of the tubes, with plastic discs on them. Simulated GF/ IF/ Distilled
water/ any sp.medium.
Time required for complete disintegration of tablets and fragments to pass # 10 sieve.
If any residue remains, it must have a soft mass, not firm core. Normally Time limit is 5 30
mins.
Limitation as per IP
Conduct 6 tablets at time note done the average time if any tablet is more than Specified time
repeat the tests with 12 tablets. Out of 18 tablet 16 tablets should pass.
The disintegration of enteric-coated tablets:
1) To be tested in simulated gastric fluid (SGF) for one hour after which no sign of
disintegration, cracking, or softening must be seen.
37

2) To be tested in simulated intestinal fluid (SIF) for the time (usually, 1 h) stated in the
individual monograph
9.TABLET DISSOLUTION TEST
The importance of in vitro dissolution test
To guide the formulation and product development process toward product optimization
To monitor the performance of manufacturing process
To assure bioequivalence from batch to batch
As a requirement for regulatory approval for product marketing for products registered with
the FDA and regulatory agencies of other countries.

The formulation and manufacturing factors affecting the dissolution of a tablet

The particle size of the drug substance
The solubility and hygroscopicity of the formulation
The type and concentration of the disintegrant, binder and lubricant used
The manufacturing method, particularly, the compactness of the granulation and the
compression force
Different types of apparatus are used to study the dissolution test of the tablet.
As per IP apparatus I (paddle) and apparatus II(basket) are used.
But as per USP dissolution apparatus used are
USP 30 classification

i. Rotating Basket (Ph.Eur./BP/JP)

ii. Paddle (Ph.Eur./BP/JP)
iii. Reciprocating Cylinder (Ph.Eur.)
iv. Flow Through Cell (Ph.Eur./BP/JP)
v. Paddle Over Disk (Ph.Eur.)
vi. Rotating Cylinder (Ph.Eur.)
vii. Reciprocating Holder
The dissolution time and rate is compared to the values mentioned in the
monograph.

The in-process variables

TABLET DISSOLUTION TEST
USP dissolution apparatus 2
USP dissolution apparatus 1

PADDLE METHOD
BASKET METHOD
38

Apparatus 1 and 2 in IP/USP

are used principally for immediate release solid dosage forms
consist of a variable speed stirrer motor, a cylindrical stainless steel basket on a stirrer shaft
(apparatus 1) or a paddle as the stirring element (apparatus 2), a 1000-ml vessel of glass fitted
with a cover having a center port for the shaft of the stirrer, and three additional ports, two for
the removal of samples, one for the placement of a thermometer, and a suitable water bath to
maintain the temperature of the dissolution medium in the vessel.
Test method (24 TABLETS)
a) A volume of the dissolution medium is placed in the vessel and allowed to come to
37oC0.5oC.
b) The stirrer is rotate at the specified speed.
c) At stated intervals, samples of the medium are withdrawn for chemical analysis time
limitation is 60 minutes
Requirement for rate of dissolution
Stage 1 T1; six tablets are tested & accepted if each of them is not less than the monograph
specified limit +5% (p+5%).
Stage 2 T2; If the dosage form fails T1 then additional six tablets are tested. The results is
acceptable if the average of the 12 tablets is greater than or equal to P , and none of them is
less than( P-15%).
Stage 3 T3; If the tablets fails the test, then additional twelve (12) tablets are tested & are
accepted if the average of all the twenty four is greater than or equal to P, If not more than
two are two are less than P-15% and none of them is less than P-25%.
Interpretation of data
The results are expressed in terms of concentration of the drug versus time
The value for t50%,t90% and % dissolved in 30 minutes are used guide lines.
A value of t90% at 30 minutes considered at be satisfactory
As per USP t 75% for tablets should be 45 minutes.
Inconsistencies in dissolution
occur not between dosage units from the same production batch, but rather between batches
or between products from different manufacturers.

References
1.Lachman L., Liberman H. and Kanig J.; The Theory and Practice of
Industrial Pharmacy; Third Edition: 293-345, 346-373.
39

2.Aulton M.; Pharmaceutics: The Science of Dosage Form Design;

International Student Edition: 304-321, 347-668.
3.Lachman L., Liberman L. and Schwartz J.; Pharmaceutical Dosage Forms:
Tablets; Second Edition : Volume I.
4.Remington J., Remington: The Science and Practice of Pharmacy; Nineteenth
Edition: Volume II : 1615-1641.
5. Banker G. and Rhodes C.;
Drug and Pharmaceutical Sciences: Modern Pharmaceutics; Third Edition; Volume
72: 333-394.
6. Martin E.; Dispensing of
Medication; Edition Seventh: 740-741.
7. Lachman L., Liberman L. and Schwartz J.;
Pharmaceutical Dosage Forms: Tablets; Second Edition : Volume II.
8. Indian Pharmacopoeia; 1996.
9.British Pharmacopoeia;2001.
10. The United State Pharmacopoeia 24; The National Formulary 19; 2000.

40