TABLETS

Content

• Definition
• Tablet types
• Tablet excipients
• Methods of Preparation
• Tabletting machine types
• Tabletting processing problems
• Tablet evaluation
• Tablet coating
 References

• Pharmaceutics-the science of dosage form design

• Remingtons pharmaceutical sciences

• Bentley‘s textbook of Pharmaceutics

 Definition

• Tablets are solid dosage forms consisting of active ingredient(s) and suitable
pharmaceutical excipients.
• Tablets may vary in size, shape, weight, hardness,
thickness, disintegration, and dissolution
characteristics and in other aspects, depending on their
intended use and method of manufacture.
 Types of Tablets

• Conventional compressed
• Multiple compressed
• Enteric coated
• Sugar coated
• Film coated
• Chewable
• Effervescent
• Buccal and sublingual
• Vaginal
• Molded
• Modified release
 Advantages of Tablets

• They are convenient to use

• A wide range of tablet types is available, offering a range of drug release rates
and durations of clinical effect.
• Tablets may be formulated to release the therapeutic agent at a particular site
within the GIT to reduce side effects, promote absorption and provide local
effect.
• They are inexpensive dosage form
• They may be formulated to contain more than one therapeutic agent.
 Advantages
• It is easier to mask the bitter taste of drug better than other dosage forms.
eg. Liquids
• The chemical, physical and microbiological stability of tablet dosage forms
are superior to other dosage forms.
• They may be easily manufactured to show product identification.
Disadvantages of Tablets

• The absorption of therapeutic agents from tablets is dependent on physiological

factors, eg. gastric emptying rate.
• The compression properties of certain drugs are poor and may present problems
in their subsequent formulation and manufacture as tablets.
• The manufacture of tablets is cumbersome as it requires a series of unit
operations.
• Production losses may be high.
• Some patients may have difficulty swallowing especially children and the
elderly.
Tablet Excipients

The following excipients are employed:

1. Diluents/Fillers
2. Binders
3. Disintegrants
4. Lubricants
5. Glidants
 Diluents

Diluents are employed in tablet formulation to increase

the mass of the formulation thereby rendering the
manufacturing process reliable and reproducible.
Examples are:
• Lactose – anhydrous, monohydrate, spray-dried
• Starch – pregelatinized
• Dibasic calcium phosphate
• Microcystalline cellulose (MCC)
• Mannitol
• sucrose
• Powdered cellulose
• Sorbitol
• Calcium carbonate
• Glucose
Binders

• Binders are substances (polymers) that are employed in tablet

formulation by the wet granulation method. They are added either as a
solution or in a powdered form.
Examples are:
• Acacia gum - 2-10% w/w
• Tragacanth gum – 2-10% w/w
• Methylcellulose - 2-10% w/w
• Sucrose - 10-50% w/w
• Hydroxypropylmethylcellulose (HPMC) – 2-5% w/w
• Hydroxypropylcellulose (HPC) - 2-6% w/w
• Polyvinylpyrolidone (PVP) - 0.5-5% w/w
Disintegrants
• They are added in tablet formulation to ensure that the tablet breaks up into small
fragments when in contact with a liquid. This promotes rapid drug dissolution.
They are required in concentrations of 5-20% w/w.
Examples are:
• Starch
• Sodium starch glycolate
• Microcystalline cellulose
• Croscarmellose sodium
• Polyvinylpyrolidone (crospovidone)
• Methylcellulose
 Lubricants
• During compression lubricants act at the interface between the face of the die and the
surface of the tablet and act to reduce the friction at this interface during ejection of the
tablet from the tablet press.
• Some lubricants are soluble whiles others are not.

Examples are:

• Magnesium stearate – 0.25-1% w/w

• Stearic acid – 1-3% w/w
• Glyceryl behenate – 1-3% w/w
• Glyceryl palmitostearate – 1-3% w/w
• Polyethylene glycol (PEG 4000, 6000, 8000)

• Sodium lauryl sulphate – 1-2% w/w

•
 Functions of Lubricants in tablet formulation
• Improve the flow of granules in the hopper to the die
cavity.
• Prevent sticking of tablet formulation to the punches
and dies during compression.
• Lubricants reduce the friction between the tablet and
the die wall during the tablet’s ejection from the tablet
machine.
• Lubricants give a sheen to the finished tablets.
Glidants
• Glidants act to enhance the flow properties of the powders within the hopper and
into tablet die in the tablet press. They also reduce friction between the
powders/granules and the surfaces of the dies and hopper. They are mainly
hydrophobic and therefore the concentration used is very critical.
Examples are:

• Talc – 1-2% w/w

• Magnesium stearate - < 1% w/w
• Colloidal silicon dioxide 0.1-0.5% w/w
Types of tablets

Disintegrating tablets
The most common type of tablet is intended to be swallowed and to
release the drug in a relatively short time thereafter by disintegration
and dissolution, i.e. the goal of the formulation is fast and complete
drug release in vivo.
Such tablets are often referred to as conventional or plain tablets.
A disintegrating tablet includes normally at least the following types
of excipients: filler (if the dose of the drug is low), disintegrant,
binder, glidant, lubricant and anti-adherent
Chewable tablets

• Chewable tablets are chewed and thus are mechanically

disintegrated in the mouth.
• The drug is, however, normally not dissolved in the mouth
but swallowed and dissolves in the stomach or intestine.
• Thus, chewable tablets are used primarily to accomplish a
quick and complete disintegration of the tablet – and hence
obtain a rapid drug effect – or to facilitate the
administration of the tablet.
• Chewable tablets are similar in composition to conventional
tablets except that a disintegrant is normally not included in
the composition.
• Flavouring and colouring agents are common and sorbitol
and mannitol are common examples of fillers
Effervescent Tablets

• Effervescent tablets are dropped into a glass of water before

administration, during which carbon dioxide is liberated.
• This facilitates tablet disintegration and drug dissolution;
the dissolution of the tablet should be complete within a few
minutes.
• As mentioned above, the effervescent carbon dioxide is
created by a reaction in water between a carbonate or
bicarbonate and a weak acid such as citric or tartaric acids
Compressed lozenges

• Compressed lozenges are tablets that dissolve slowly in the

mouth and so release the drug dissolved in the saliva.
• Lozenges are used for systemic drug uptake or for local
medication in the mouth or throat, e.g. with local
anaesthetic, antiseptic and antibiotic drugs.
• The latter type of tablets can thus be described as slow-
release tablets for local drug treatment.
Prolonged-release tablets

• After release from the tablet, the drug should normally be absorbed into
the systemic circulation.
• The aim is normally to increase the time period during which a
therapeutic drug concentration level in the blood is maintained.
• However, the aim can also be to increase the release time for drugs that
can cause local irritation in the stomach or intestine if they are released
quickly.
• Examples of the latter are potassium chloride and iron salts. In addition,
drugs for local treatment of diseases in the large intestine are sometimes
formulated as prolonged-release
Types of tablets
 Methods of Preparation

• Tablets are generally prepared by one of the following methods:

1. Wet granulation
2. Dry granulation
3. Direct compression: suitable for drugs that are:
• Sensitive to heat and moisture
• Have good flow properties (flowability)
• Have compression properties (compressibility)
Direct compression tabletting
• Some granular chemicals, like potassium chloride, possess free flowing and
cohesive properties that enable them to be compressed directly in a tablet
machine without wet or dry granulation.
Classification of tablet presses
• Single-punch
• Multi-station rotary
Multi-station rotary press

The compression
is applied by both
the upper punch
and the lower
punch.
Stages in Tablet Compression
Capping

• Is the term used when the upper or lower segment of the tablet seperates
horizontally, either partially or completely from the main body of a tablet and
comes off as a cap.
Causes:
1. Large amount of fines in the granules.
2. Too dry or very low moisture content in granules.
3. Not thoroughly dried granules.
4. Insufficient amount of binder or improper binder.
5. Granular mass too cold to compress firmly.
6. Unpolished punch and die surfaces.
Lamination

• Is the separation of a tablet into two or more distinct horizontal layers.

Causes:
1. Air entrapment during compression and subsequent release on ejection.
2. Too much of hydrophobic lubricant. eg. magnesium stearate.
3. Rapid decompression
 Quality requirements for Tablets

Pharmacopeial/Official tests These factors must be

 Uniformity of weight controlled during
production (in-process
 Uniformity of content
controls) and verified after
 Thickness the production of each
 Disintegration batch to assure that
established product quality
 Dissolution
standards are met.
• Non-pharmacopeial/Unofficial tests
 Hardness
 friability
 Tablet Uniformity of weight
• The quantity of fill placed in the die of a tablet press determines the weight
of the resulting tablet.
• The volume of fill is adjusted with the first few tablets produced to yield
tablets of the desired weight.
• The USP contains a test for the determination of dosage-form uniformity
by weight variation for uncoated tablets.
• In the test, 20 tablets are weighed together and the average weight
calculated.
• The tablets are then weighed individually.
• The variation of the individual weights from the average weight is
expressed as a percentage.
• Not more than two (2) tablets should deviate by the stated percentage and
none should deviate by twice the stated percentage.
Tablet Uniformity of weight
USP BP

Average weight % Difference Average weight % Difference

130 mg or less 10 80 mg or less 10

More than 130 More than 80 mg

mg but less than 7.5 but less than 250 7.5
324 mg mg

More than 324 5 More than 250 mg 5

mg
Uniformity of content

• By the USP method, 10 dosage units are individually

assayed for their content according to the assay method
described in the individual monograph.

• The requirements for content uniformity are met if the

amount of active ingredient in each dosage unit lies
within the range of 85% to 115% of the label claim and
the relative standard deviation is less than 6.0%.
Tablet Thickness

- The thickness of a tablet is determined by the diameter of the die, the

amount of fill permitted to enter the die ， the compactability of the fill
material and the force or pressure applied during compression.

- To produce tablets of uniform thickness during batch production and

between batch productions for the same formulation, care must be
exercised to employ the same factors of fill, die, and pressure.

- Tablet thickness is determined with a caliper or thickness gauge that

measures the thickness in millimeters.
Tablet Disintegration
To be absorbed, a drug substance must be in solution, and the
disintegration test is a measure only of the time required under a
given set of conditions for a group of tablets to disintegrate into
particles.
• This test is used as a control for tablets intended to be administered
by mouth except for chewable tablets.
• Conditions:
Uncoated tablets: water at 37oC

• Tablets usually must disintegrate within 15 minutes.

• If one or more tablets fail to disintegrate, additional tests

prescribed by the USP must be performed.

• Enteric-coated tablets are similarly tested, except that the tablets

are permitted to be tested in simulated gastric fluid for one hour
after which no sign of disintegration, cracking, or softening must
be seen.
Tablet Dissolution

Dissolution test measures the amount of time required for a given

percentage of the drug substance in a tablet to go into solution under a
given set of conditions.
• It is a test intended to provide an evaluation of the physiological
availability of the drug Conditions: USP Apparatus II
• Paddle speed: 50, 75, 100 rpm
• Temperature: 37oC
• Sampling times: 5, 10, 15, 30, 45 and 60
mins
BP
• For uncoated tablets, 75% of the stated
amount of drug should dissolve within 45
minutes.
USP
• 85% dissolution within 30 minutes
In vitro dissolution testing of solid dosage forms is important for a
number of reasons.

- It guides the formulation and product development process toward

product optimization.

- The performance of the manufacturing process may be monitored

by dissolution testing.

- Consistent in vitro dissolution testing results assure bioequivalence

from batch-to-batch.

- It is a requirement for regulatory approval for product marketing

and product registration with regulatory agencies.
 Factors that may influence dissolution

Formulation and manufacturing factors that can affect the

disintegration and dissolution of a tablet include:
• The particle size of the drug substance in the formulation.
• 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 used in tableting.
Tablet hardness

• Tablets require a certain amount or strength or hardness to withstand

mechanical shocks of handling in manufacture, packaging and shipping.
• It is defined as the force required to break a tablet in a diametric
compression test.
Test:
A tablet is placed between two anvils and the crushing strength that just
causes the tablet to break is recorded.
Tablet Testers:
1. Monsanto tester
2. Strong-Cobb tester
3. Pfizer tester
4. Erweke tester
5. Schleuniger tester
A force of about 4 Kg is considered the minimum requirement
for a satisfactory tablet
Tablet friability
• Tablet hardness is an absolute indicator of tablet strength since some formulations
when compressed into hard tablets may chip or crack. Another measure of tablet
strength is friability.

Test
About 10 tablets are selected and
weighed.
• The tablets are put in the friabilator
and for 4 minutes (100 revolutions).
• The tablets are dedusted and
reweighed.
• Any loss in weight is determined.
• Loss in weight should not be more
than 1%.
 Technical problems during tabletting

• High weight and dose variation of the tablets

 Check die volume and compression force, poor flow of granules, different granule
sizes/densities
• Low mechanical strength of the tablets

 Check compression force

• Chipping

 Check machine settings, dry granules, excess binder

• Capping and lamination of the tablets

• Adhesion or sticking of powder material to punch tips – poor lubrication, wrong choice of
lubricant, film of fines
• High friction during tablet ejection

• Protracted disintegration – strong

granulating agent, high degree of compaction (hard
tablets), hydrophobicity (lubricant), wrong or inappropriate/inadequate
• Drug instability – dry air, moisture content of granules
• As the production manager, you developed a formula for an anti-helminthic
compressed tablet. During the initial run, the tablets were found to be too friable.
What can be done?
• Objective Information
• The formula for the tablet is as follows:
• Anti-helminthic….. 50 mg
• Directly compressible lactose…… 150 mg
• Magnesium stearate…… 10 mg
• Starch…….. 100 mg
• Talc …….25 mg
• The tablet is to be compressed, so it has the following
characteristics:
• Description 8-mm white biconvex bisected tablet Weight
335 mg
• Hardness 8 kg
• Dissolution Medium: 0.01 N hydrochloric acid, 500 mL
Apparatus 2: 50 rpm Time: 30 minutes
Formular for calculating friability

• W1 = Weight before test

• W2 = Weight after test
• Percentage friability = W1 – W2 X 100
W1
The loss in weight should not exceed 1%
Tablet Coating
• Tablet coating is the application of a coating material to the exterior of a tablet
with the intention of conferring benefits and properties to the dosage form over
the uncoated variety.
• Reasons for tablet coating:
1. Protecting the drug from degradation by air, moisture and light in order to improve
stability.
2. Masking unpleasant taste and odour
3. Making it easier for the patient to swallow the tablet
4. Improving product identity
5. Facilitating handling especially in high speed packaging or filling lines.
6. Improve product appearance
7. Modifying drug release as in enteric-coated, repeat-action and sustained-release
products.
8. To target drug release to a specific site in the GIT.
Types of Coating

• Sugar coating
• Film coating
• Enteric coating
• Compression coating
Main stages of coating:
• The tablets are placed in the coating apparatus and agitated.
• The coating solution is sprayed onto the surface of the tablets.
• Warm air is passed over the tablets to facilitate removal of the solvent from
the adsorbed layer of coating solution on the surface of the tablets.
• When the solvent has evaporated, the tablets will be coated with the solid
component of the original coating material.
Tablet Coating Machine
Coating formulation
• Two main formulation types:

1. Solutions
2. Emulsions

Typically comprises of
• Polymer – used to make the film. e.g. HPMC, MC, HPC, methacrylate copolymers (Eudragit – L, S, FS, and E
---- RS and RL)

• Plasticizer – used to increase flexibility in the coating, reduce film cracking and improves adhesion of the film
to the tablet. e.g. glycerin, propylene glycol, polyethylene glycol, triacetin, phthalate esters

• Colourants – to improve appearance and facilitate product identification. e.g. Iron oxides, caramel,
carotenoids, flavones, tartrazine, sunset yellow, erythrosine, amaranth,

• Solvent – aid in the application of the coat to the tablet surface e.g alcohols, ketones, esters, chlorinated
hydrocarbons, water
Sublingual tablets and buccal tablets

• Sublingual tablets and buccal tablets are used for drug

release in the mouth followed by systemic uptake of the
drug.
• A rapid systemic drug effect can thus be obtained without
first-pass liver metabolism.
• Sublingual tablets are placed under the tongue and buccal
tablets are placed in the side of the cheek or high up
between the inside of the upper lip and gum
Sugar coating
- This imparts a smooth, rounded and elegant appearance to the
tablet.
-Sugar-coating relies primarily on the use of sucrose.
The sugarcoating of tablets may be divided into the following steps:
- waterproofing and sealing: the sealing coat is applied to the tablet
to separate the tablet ingredients from water. It is also to strengthen
the tablet core. e.g. using alcoholic solutions of shellac, gelatin,
acacia, cellulose acetate phthalate or polyvinyl acetate phthalate.
- Sub-coating: this is the critical operation in sugar-coating. Gum
solutions (sucrose + acacia/gelatin) are mostly applied and weight
build-up is done at this stage as well as uniform edges.
- smoothing and final rounding: this is usually
accomplished by the application of a simple syrup
solution (60-70%).
- finishing and coloring if desired: Dyes or pigments are
used.
- Polishing: sugar-coated tablets are dull in appearance
and thus require polishing to achieve final elegance.
Waxes (beeswax, carnauba wax, candelila wax or hard
paraffin) are used.
- Printing: this is branding with inks.
•The sugar-coating process is tedious, time-consuming, and
requires the expertise of highly skilled technicians.
•It results in coated tablets that may be twice the size and
weight of the original uncoated tablets,
•Sugar-coated tablets may vary slightly in size from batch to
batch and within a batch.
• The sugar-coating process is tedious, time-consuming, and requires the expertise of
highly skilled technicians.
• It results in coated tablets that may be twice the size and weight of the original
uncoated tablets,
• Sugar-coated tablets may vary slightly in size from batch to batch and within a batch.

• The film-coating process places a thin, skin-tight coating of

a plastic-like material over the compressed tablet. Film-
coated tablets have essentially the same weight, shape, and
size as the originally compressed tablet.
• The coating is thin enough to reveal any identifying
monograms embossed in the tablet during compression by
the tablet punches.
• Film-coated tablets are also far more resistant to
destruction by abrasion than are sugarcoated tablets.
• Film-coating solutions may be non-aqueous or
aqueous. The non-aqueous solutions contain
- A film former – ethylcellulose, PVP
- A plasticizer
- A surfactant
- Opaquants and colorants