SOLID DOSAGE FORMS

Padma Gosh.D
DOSAGE FORMS

 Dosage forms can be defined as formulations.

 Drugs cannot be intented as such , have to be converted to

necessarily forms called as formulations

 Dose of the drug may be defined as the quantity

of drug which is enough (optimum theraputic
effect in lowest possible dose)
 Posology
Types of dosage forms

 Solid dosage forms

 Liquid dosage forms

 Semisolid dosage forms

Examples for Dosage forms

 Solids - Tablets, Capsules,Powders,

Granules,lozenges, pessaries, suppositories&
Insufflation etc.
 Liquids – Injection , Syrups, Paints,
Lotions,Emulsion, Suspension , Gargles,
Ear&Eye drops, Enemas& Liniments etc.
 Semisolids- Ointments, cream, paste& jellies.
Solid dosage forms

 TABLETS:
May be defined as solid dosage form
which contain one or more medicaments with or
without diluents and other additives and prepared
either by molding or by compression.
ADVANTAGES

 Unit dosage form.

 Tamper proof dosage form .
 Great precision and least content variability
 Cost is lowest of all dosage forms.
 Product identification is simplest and cheapest as
monogram or punching can be applied.
 Flexibility of dosage forms (bisected tablets)
 Special release profile can be formulated such enteric
coated or delayed release .
Disadvantages

 Some drug resist compression into dense

components.
 Drugs with poor wetting , slow dissolution
properties, intermediate to large dosage , may be
difficult to formulate.
 Bitter taste drugs & drugs with objectionable
odour, drugs that are sensitive to oxygen or
atmospheric moisture may require encapsulation
or entrapment prior to compression or even
coating then tablets may be costly.
Properties of tablets

 Should be elegant product , while being free of defects

such as chips, cracks, discoloration. Contamination etc.
 Should have strength to with stand rigors of mechanical
shocks encountered in production, packing and shipping
and dispensing.
 Should have smooth surface, good appearance , cohesive
and compact so that they do not under go friability,
powdering or chipping in the bottle during shipping or
handling…..
Properties of tablets

 Must have a suitable chemical stability over the

time so as not to allow alteration of the medical
agent
 Must be able to release the chemical agent in the
predictable and responsible manner.
Types of tablets

 Oral tablets
 Chewable tablets
 Buccal /Sublingual tablets
 Lozenges
 Effervescent tablets
 Implants
 Enteric coated tablets….
Types of tablets

 Sustained release tablets

 Sugar coated tablets
 Film coated tablets.
 Layered tablets
 Etc..
Size and shape

 Size and shape can be dimensionally described,

monitored and controlled.
 The thickness of the only dimensional variable related to
the process.
 At constant comprehensive load, tablet thickness varies
with change in the die fill
 With constant die, fill thickness varies with variation in
compression load.
Organoleptic properties.

 Many pharmaceutical products use color as vital

means of rapid identification and consumer
acceptance.
 The color of the product must be uniform with in
a single tablet (non uniformity is generally
referred to as mottling) from tablet to tablet and
from lot to lot…..
Organoleptic properties

 Color standards themselves are subject to change

with time, thus forcing their frequent redefinition,
which can lead to a gradual and significant
change in acceptable color.
 The presence of an odour in a batch of tablets
could indicate a stability problem, such as the
characteristic odor of acetic acid in degrading
aspirin tablets…..
Organoleptic properties.

 Taste is important in consumer acceptance of

chewable tablets
 Owing to the subjectivness of taste preference
how ever the control of taste is often simply
presence or absence of specified taste .
Formulations of tablets

 Diluents
 Binders
 Granulation agents
 Disintegrating agents
 Lubricants
 Coloring agents
 Flavoring agents
 Sweetening agents
Preparation of tablets

 Direct compression
 Dry granulation
 Wet granulation
Compression of tablets
Tablets processing problems

 Capping, Sticking, Mottling and Tablet

weight variation.
CAPPING AND LAMINATION

 Capping:- Partial or complete

separation of top or bottom
crowns of tablet main body.
 Lamination:- Separation of a tablet into
two or more distinct layers.
Friability test can be used to reveal
these problems
PICKING AND STICKING

Picking
Adherence of the tablet material from the
surface of a tablet by a punch

Reasons:
• Because of engraving or embossing
on the punch tips like small enclosed areas in
the letters like “A”, “B”, “D”,
“O”, “Q” etc
Sticking

Sticking
Adherence of tablet material to the die walls
resulting in chipping of tablet
edges producing rough edges and causing the
lower punches uneasy to move resulting
in damage of cam tracks and punch faces

Reasons:
• Presence of low melting point substances
in the formula eg. Stearic acid, PEG
(Polyethylene glycol) etc , which gets soften
due to compressive heat
• Excessive moisture in the granules
Mottling

 Unequal distribution of color on the tablet surface with light

and dark areas standing out in an otherwise uniform
colored surface .
 Reasons:
• Variation in the colors of ingredients (drug and other
additives)
• Drugs with degradation nature and have different colored
degraded products
• Migration of dye to the surface of granulation during drying
• Uneven distribution of colored adhesive gel solutions
resulting in precipitation.
 Double impression

Reason:

Uncontrolled movement of punches with

engravings on them

Remedy:

Using anti-turning devices

Coating

 Sugar coating
 water proofing
 Sub coating
 Smoothing
 Coloring
 polishing
 Film coating
 Compression coating
 Enteric coating
 Micro encapsulation
Evaluation of tablets

 To design tablets & later monitor their quality,

quantitative evaluation, assessment of tablet’s
physical, chemical and bioavailability properties
must be carried out.
 Tablet thickness is consistent in batch to batch or
within a batch only if the tablet granulation or
powder blend is adequately consistent in particle
size and size distribution….
Evaluation of tablets

 Hardness and friability.

 Tablets require a certain amount of strength or hardness
and resistance to friability, to withstand mechanical shocks
of handling in manufacture, packaging and shipping.
 One of the earliest testers to evaluate tablet hardness was
the Monsanto hardness tester, which was developed
approximately 50 years ago.
Weight variation

 The weight of the tablet being made is routinely measured

to help ensure that the tablet contains proper amount of
drug.
 USP weight variation is done by weighing 20 tablets
 The tablets meet USP test if no more than 2 tablets are
outside the percentage limit and if no tablet differs by
more than 2 times the percentage limit…
Average weight of tablets Maximum percentage
(mg) difference allowed

Average weight of
tablets (mg)
130 Maximum
or less 10
percentage
difference
130-324allowed 7.5
130 or less 10
130-324 7.5
More than 324 5
More than 324 5
Weight variation

 Weight variation method would be a satisfactory method

of determining the drug content uniformity of tablets.
 Three factors can directly contribute to content
uniformity problems in tablet

1. Non-uniform distribution of the drug substance

throughout the powder mixture or granulation
2. Segregation of the powdered mixture or granulation
during the various manufacturing processes .
3. Tablet weight variation…
Weight variation

 In tablets with smaller dosages, a good weight

variation does not ensure good content
uniformity, but a large weight variation precludes
good content uniformity.
 COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL TESTS

PHARMACOPOEIAS TYPE OF TABLET TESTS TO BE PERFORMED

BRITISH For all tablets Content of active ingredients, Disintegration, Uniformity of content, Labeling
PHARMACOPOEIA
Uncoated tablet Disintegration test, Uniformity of weight
PHARMACOPOEIAS TYPE OF TABLET TESTS TO BE PERFORMED
BRITISH PHARMACOPOEIA For all tablets Content of active
Effervescent tablet
ingredients, Disintegration, Uniformity of content, Labeling Disintegration test, Uniformity of weight
Uncoated tablet Disintegration test, Uniformity of weight
Effervescent tablet Coated tablet Disintegration test, Uniformity of weight
Disintegration test, Uniformity of weight
Coated tablet Disintegration test, Uniformity of weight
Gastro resistant tablet
Gastro resistant tablet Disintegration test Disintegration test
Modified release tablet Uniformity of weight
Modified release tablet Uniformity of weight
Tablet for use in mouth Uniformity of weight
Soluble tabletDisintegration test, Uniformity of weight
Tablet for use in mouth Uniformity of weight
Dispersible tablet Disintegration test, Uniformity of
dispersion, Uniformity of weight
INDIAN Soluble tablet Disintegration test, Uniformity of weight
PHARMACOPOEIA Uncoated tablet Uniformity of container content, Content
of active ingredient, Uniformity of weight, Uniformity of content,
Disintegration test
Enteric coated tabletDispersible tablet Disintegration test Disintegration test, Uniformity of dispersion, Uniformity of weight
Dispersible tablet Uniformity of dispersion, Disintegration
INDIAN Soluble tabletDisintegration test Uniformity of container content, Content of active ingredient, Uniformity of weight, Uniformity of content, Disintegration
Effervescent tablet Uncoated tablet Disintegration/ Dissolution / Dispersion
test
PHARMACOPOEIA test
UNITED STATES PHARMACOPOEIA Physical tests applicable to tablet
formulation Bulk density /Tapped
Enteric coated density of powder, Powder fineness,
tablet Loss
Disintegration test
on drying , Disintegration test, Tablet friability, Dissolution test, Drug release
testing, Uniformity of dosage form, Container permeation test, Labeling of
inactive ingredients Dispersible tablet Uniformity of dispersion, Disintegration

Soluble tablet Disintegration test

Effervescent tablet Disintegration/ Dissolution / Dispersion test

UNITED STATES
PHARMACOPOEIA Physical tests applicable to tablet formulation
Bulk density /Tapped density of powder, Powder fineness, Loss on drying , Disintegration test, Tablet friability, Dissolution
test, Drug release testing, Uniformity of dosage form, Container permeation test, Labeling of inactive ingredients
Content uniformity test.

 To assure uniform potency for tablets of low dose drugs, a

content uniformity test is applied in this test, 30 tablets are
randomly selected or the sample and at least 10 of them
are assayed individually.
 9 of the 10 tablets must contain not less than 85% or more
than 115% of the labeled drug content.
 The 10th tablet may not contain less than 75% or more
than 125% of the labeled content….
Content uniformity test.

 If these conditions are not met the tablets

remaining from the 30 must be assayed
individually, and none may fall outside the 85 to
115% range. In evaluating a particular lot of
tablets, several samples of tablets should be taken
from various parts of production run to satisfy
statistical procedures.
CU calculation
For L1

T≤101.5 If 98.5 %≤X≤101.5 %

M=X (AV=ks)

If X < 98.5 % M=98.5 %

AV= 98.5 – X + ks

If X > 101.5 % M=101.5 %

AV= X-101.5 + ks

T - Assay
X -Mean of individual contents expressed as a percentage of label claim
AV -Acceptance value
k -Acceptability constant
s - Sample standard deviation
M -Reference value
Disintegration

 A generally accepted maxim is that for a drug to

be readily available to the body, it must be in
solution form.
 For most tablets, the first important step towards
solution is breaking down of the tablet into
smaller particles or granules, a process known as
disintegration
Dissolution

 The rate of drug absorption for acidic drug

moieties that are absorbed high in the GIT is often
determined by the rate of drug dissolution from
the tablet .
 The rate of dissolution may thus be directly
related to the efficacy of the tablet product, as
well as to bioavailability differences between
formulations….
Dissolution

 Therefore an evaluation as to whether or not a

tablet releases its drug contents when placed in
the environment of the GIT is often a fundamental
concern.
 The most direct assessment of a drug’s release
from various tablet formulations or products is
accomplished through in-vivo bioavailability
measurements….
Dissolution

 Two objectives in the development of the in-vitro

dissolution tests are to show.
1. That the release of drug from the tablet is as close as
possible to 100%.
2. That the rate of drug release is uniform batch to batch
and is the same as the release rates from those batches
proven to be bioavailable and clinically effective.
The End