TABLETS

Solid-dosage forms broadly encompass two types of formulation, namely tablets and capsules. It has been
estimated that solid-dosage forms constitute circa 90% of all dosage forms used to provide systemic
administration of therapeutic agents. The term ‘tablet’ (from Latin tabuletta) is associated with the
appearance of the dosage form, i.e. tablets are small disc-like or cylindrical specimens.

Tablets are defined as ‘solid preparations each containing a single dose of one or more active substances.
They are obtained almost always by compressing uniform volumes of particles and their shape and size are
determined by the use of various shaped punches and dies (sometimes by another suitable manufacturing
technique, such as extrusion, molding or freeze-drying).

Some tablets are scored, or grooved, which allows them to be easily broken into two or more parts. This
enables the patient to swallow smaller portions as may be desired, or when prescribed, it allows the tablet to
be taken in reduced or divided dosage. Some tablets that are not scored are not intended to be broken or cut
by the patient since they may have special coatings and/or drug-release features that would be
compromised by altering the tablet’s physical integrity.

Tablets are used mainly for systemic drug delivery but may also be used for local drug action.

Advantages of Tablets
 The oral route represents a convenient and safe way of drug administration.
 Compared to liquid dosage forms, tablets (and other solid dosage forms) have general advantages in
terms of the chemical, physical and microbiological stability of the dosage form.
 A wide range of tablet types is available, offering a range of drug release rates and durations of
clinical effect. Tablets may be formulated to offer rapid drug release or controlled drug release, the
latter reducing the number of daily doses required (and in so doing increasing patient compliance).
 Tablets may be formulated to release the therapeutic agent at a particular site within the
gastrointestinal tract to reduce side effects, promote absorption at that site and provide a local effect
(e.g. ulcerative colitis). This may not be easily achieved by other dosage forms that are administered
orally.
 Tablets may be formulated to contain more than one therapeutic agent (even if there is a physical or
chemical incompatibility between each active agent). Moreover, the release of each therapeutic agent
may be effectively controlled by the tablet formulation and design.
 With the exception of proteins, all classes of therapeutic agents may be administered orally in the
form of tablets.
 It is easier to mask the taste of bitter drugs using tablets than for other dosage forms, e.g. liquids.
 Tablets are generally an inexpensive dosage form.
 Tablets may be easily manufactured to show product identification, e.g. exhibiting the required
markings on the surface
Disadvantages of Tablets
 Poor bioavailability of drugs due to unfavourable drug properties, e.g. poor solubility, poor
absorption properties
 The compression properties of certain therapeutic agents are poor and may present problems in
their subsequent formulation and manufacture as tablets.
 The administration of tablets to certain groups, e.g. children and the elderly, may be problematic due
to difficulties in swallowing
 Some drugs that cause local irritant effects can cause more harm to the gastrointestinal mucosa
when administered as tablets.

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Types of Tablets
A common means of classifying tablets is based on the drug release pattern from the tablets. The
following categories are often used in this context: immediate release, prolonged (sustained) release,
pulsatile release and delayed release. The latter three types are also referred to as modified-release tablets.
For immediate-release tablets, the drug is intended to be released rapidly after administration, or the tablet
is dissolved in liquid before intake and thus administered as a solution.
Immediate-release tablets are the most common type of tablet and include disintegrating, chewable,
effervescent, sublingual and buccal tablets. Modified-release tablets should normally be swallowed intact.
The formulation and thus also the type of excipients used in such tablets might be quite different from those
of immediate-release tablets.
The term prolonged-release tablet is used to indicate that the drug is released slowly at a nearly constant
rate.
A pulsatile release tablet is another means to increase the time period for drug absorption after a single
administration and is accomplished by releasing the drug in two or more pulses.
For delayed-release tablets the drug is liberated from the tablet sometime after administration. After this
period has elapsed, the release is normally rapid.

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Comparison between release profiles and plasma profiles of tablet types classified according to
release pattern.

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0 1 2 3 4 5 6

Relation between percent of drug released from the tablet and time in hours

10
9
8
7
6
5
4
3
2
1
0
0 1 2 3 4 5 6

Relation between conc. of drug in plasma and time in hours

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Another method of classifying tablets is according to method of manufacture and intended use
Conventional compressed tablets
These tablets are designed to provide rapid disintegration and hence rapid drug release, and represent a
significant proportion of tablets that are clinically used. The manufacture of these tablets involves the
compression of granules or powders (both containing drug) into the required geometry. Following ingestion,
the tablets will disintegrate within the gastrointestinal tract (stomach), allowing the drug to dissolve in the
gastric fluid and, ultimately, be absorbed systemically.
Multiple compressed tablets
These are tablets that are composed of at least two layers. Typically
there are two designs of multiple compressed tablets: (1) multiple-
layered; and (2) compression coated. In the former design the first layer
is formed by a relatively light compression of the drug containing
powder mix/granules. The next layer is then formed by compression of
the powder/granule mix containing drug) on top of the lightly
compressed first layer. Additional layers are formed in a similar fashion.
In the second approach the initial layer is prepared by light compression
(as described above), removed and located in a second tablet press. The
granules/powders of the second coat are fed into the press and allowed
to form a constant mass around the surface (and edges) of the pressed tablet prior to compression to form
the finished product. It is, of course, possible to prepare tablets containing more than two layers although, in
so doing, the complexity of the manufacturing process is dramatically increased.
There are several applications of the use of multiple compressed tablets, including:
 The separation of drugs into separate layers that may be incompatible when formulated as a (single-
layer) Conventional tablet
 The delivery of therapeutic agents at different rates or to different sites within the gastrointestinal
tract from a single tablet.
 May be simply for the unique appearance of the layered tablet.
 The production of tablets that are coated. This is important in cases where the drug has a bitter taste
or where the drug is irritant to the stomach or is chemically unstable under acidic conditions.
Enteric-coated tablets
These are tablets that are coated with a polymer that does not dissolve under acidic conditions (i.e. the
stomach) but does dissolve under the more alkaline conditions of the small intestine.
Enteric polymers are primarily employed as coatings of conventional tablet dosage forms and, by inhibiting
the dissolution of the therapeutic agent within the stomach, offer protection against possible drug
degradation (e.g. erythromycin) or irritation of the gastric mucosa (e.g. non-steroidal anti-inflammatory
drugs). Following dissolution of the coating, the tablet will disintegrate and the drug will dissolve in the
intestinal fluids (thereby facilitating absorption).
Sugar-coated tablets
These are conventional tablets that have been coated with a concentrated sugar solution to improve the
appearance of the formulation and/or to mask the bitter taste of the therapeutic agent. The use of sugar
coatings has dramatically decreased due to the time and expertise required in the coating process and the
increase in size, weight, and shipping costs. Sugarcoating may add 50% to the weight and bulk of the
uncoated tablet.
Film-coated tablets
These are conventional tablets that have been coated with a polymer or a mixture of polymers. Film coatings
show improved mechanical properties when compared to sugar coatings and, furthermore, film coatings
may be deposited over embossed markings on the tablet surface. Film coatings are generally less elegant
than sugar coatings but have the advantage over sugar coatings in that it is more durable, less bulky, and less
time consuming to apply.
In addition to improving the appearance of conventional tablets, film coatings are employed to control the
rate and duration of drug release or to target drug release to certain regions of the gastrointestinal tract, e.g.
the colon. If the film coating is insoluble, the tablet will retain its shape during transit along the
gastrointestinal tract. Drug release occurs by diffusion through the insoluble coating and subsequent
partitioning into the gastrointestinal fluids.
The use of film coatings to target drug release within the gastrointestinal tract requires the use of polymers
that dissolve within certain pH ranges. For example, enteric coatings offer drug targeting to regions of the
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gastrointestinal tract in which the pH is more than 5.5. Targeting drug release to the colon involves the use
of polymer coatings that dissolve at higher pH values (more than 7).

Chewable tablets
As indicated by the name, these tablets are chewed within the buccal cavity prior to swallowing. The main
applications for this dosage form are:
1- for administration to children and adults who have difficulty in swallowing conventional tablets
2- Antacid formulations in which the size of the tablet is normally large and the neutralization efficacy of
the tablet is related to particle size within the stomach.
Conversely, chewable tablets are not conventionally used if the drug has problem regarding taste
acceptability.

Effervescent tablets
Effervescent tablets are added to aqueous solutions where they will rapidly disintegrate and produce either
a drug suspension or an aqueous solution. The disintegration of the tablet is due to a chemical interaction
that occurs between two components: (1) an organic acid (e.g. citric acid); and (2) sodium bicarbonate in the
presence of water. The evolution of carbon dioxide from this reaction results in tablet disintegration. The
patient then consumes the solution/suspension. The main advantage of the use of effervescent tablets is the
production of a dosage form from which the therapeutic agent is more rapidly absorbed than from
alternative solid-dosage forms (e.g. conventional tablets).
Conversely, the main disadvantages of this type of dosage form are the possible (un)availability of water and
the need to package these tablets in moisture-impermeable packaging (typically aluminum foil), to inhibit
the interaction between the acid and sodium bicarbonate due to the presence of environmental moisture.

Buccal and sublingual tablets

Buccal and sublingual tablets are dosage forms that are held within the oral cavity and allowed to dissolve;
the drug is absorbed across the buccal mucosa to produce a systemic effect. Buccal tablets are designed to
erode slowly, whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid
drug effects.
The type of tablet dictates the location within the oral cavity. Accordingly buccal tablets are positioned
between the cheek and the gingiva whereas sublingual tablets are positioned underneath the tongue. These
tablets are employed to achieve either rapid absorption into the systemic circulation (e.g. glyceryl trinitrate
sublingual tablets) or, alternatively, to enable systemic drug absorption in situations where oral drug
delivery is inappropriate, e.g. nausea. Also; Drug absorption across the buccal mucosa avoids first-pass
metabolism.
Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a
flavoring substance in a hard candy or sugar base. They are intended to be slowly dissolved in the oral
cavity, usually for local effects.

INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS

Instant-release tablets (orally dissolving tablets or ODTs) are characterized by disintegrating or dissolving in
the mouth within 1 minute, some within 10 seconds. Tablets of this type are designed for children and the
elderly or for any patient who has difficulty in swallowing tablets. They liquefy on the tongue, and the
patient swallows the liquid. A number of techniques are used to prepare these tablets, including
lyophilization, soft direct compression, and other methods. These tablets are prepared using very water-
soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution. They have
the stability characteristics of other solid dosage forms but much lower mechanical stability.
These ODTs are more convenient to carry and administer than an oral liquid. They are generally packaged in
cards or bubble-type packaging with each individual tablet in its own cavity.
Beside its advantages, there are a number of disadvantages and difficulties associated with formulating
RDTs, including drug loading, taste masking, friability, manufacturing costs, and stability of the product.
Drug loading is incorporation of the drug into the dosage form. Some RDTs are made as blanks to which a
drug is post-loaded, or added after the blank is made. Generally the drug is in solution, often in an organic
solvent (alcohol), and is added to the tablet, after which the solvent evaporates. Most drugs, however, are
incorporated into the tablets during manufacturing.

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Taste masking poses numerous challenges for RDTs. Since the drug product dissolves in the mouth, any taste
of the drug must be covered, either by a flavoring technique or by microencapsulation or Nano
encapsulation. The product also should not be gritty, which necessitates very small particle sizes if
microencapsulation is used.
Friability is an inherent problem in RDTs. For a product to dissolve instantly, it may be quite friable. Making
it more firm and less friable may increase dissolution time. A balance generally must be achieved between
friability and the speed of dissolution.

Vaginal tablets
These are ovoid-shaped tablets that are inserted into the vagina (using a special inserter). Following
insertion, retention and slow dissolution of the tablet occur, releasing the therapeutic agent to provide the
local pharmacological effect (e.g. for the treatment of bacterial or fungal infection). Vaginal tablets may also
be used to provide systemic absorption of therapeutic agents.

Tablet manufacturing
Stages in tablet formation
The dominating technique of forming tablets is by powder compression, i.e. forcing particles into close
proximity to each other by confined compression. This enables the particles to cohere into a porous, solid
specimen of defined geometry. The compression takes place in a die by the action of two punches, the lower
and the upper, by which the compressive force is applied. Powder compression is defined as the reduction
in volume of a powder owing to the application of a force. Because of the increased proximity of particle
surfaces accomplished during compression, bonds are formed between particles which provide coherence to
the powder, i.e. a compact is formed. Compaction is defined as the formation of a solid specimen of defined
geometry by powder compression. The process of tableting can be divided into three stages (sometimes
known as the compaction cycle).
1-Die filling: The formulated powders or granules are fed
(usually by gravitational flow) into the die section, i.e. in
the space between the lower and upper punches, from the
hopper on the tablet press. The volume of space occupied
by the granules/powders is defined by the position of the
lower punch and the die plate

2-Tablet formation: This stage commences with the

retraction of the shoe to facilitate access of the upper
punch to the powder/granule bed. The upper punch then
descends to the powder/granule bed, at which point a
stress is applied, thereby compressing the
powder/granule bed into a tablet. In general the lower
punch remains static during this stage; or can move
upwards in the die during the compression phase. In
addition to the choice and concentration of formulation
components, changing the stress applied to the powder or
granule bed by the upper punch alters the tablet
hardness.
After the maximum applied force is reached, the upper
punch leaves the powder, i.e. the decompression phase.

3-Tablet ejection: Following compression, the upper

punch is elevated to its original position. At this stage the
lower punch moves upwards until it is flush with the die
plate. The shoe of the hopper is then moved across the die
plate where it pushes the tablet from the lower press. Simultaneously the lower punch descends to its
starting position and granules/powders fill the volume between the shoe and the lower plate. At this point
the manufacturing sequence returns to stage 1 once more.

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Tablet excipients
In addition to the active ingredient(s), a series of excipients is normally included in a tablet; their role is to
ensure that the tableting operation can run satisfactorily and that tablets of specified quality are prepared.
Depending on the intended main function, excipients to be used in tablets are subcategorized into different
groups. Examples of substances used as excipients in
tablets are given in the Table.

Diluents/fillers
Diluents are employed in the formulation of tablets (by
all methods) to increase the mass of the tablets that
contain a low concentration of therapeutic agent and
thereby render the manufacturing process more
reliable and reproducible. Diluents must exhibit good
compression properties and be inexpensive.
Tablets normally weigh at least 50 mg. Therefore, a low
dose of a potent drug requires the incorporation of a
substance into the formulation to increase the bulk
volume of the powder and hence the size of the tablet.
This excipient is not necessary if the dose of the drug
per tablet is high.
Lactose is the most common filler in tablets. It
possesses a series of good filler properties, e.g.
dissolves readily in water, has a pleasant taste, is
nonhygroscopic, is fairly non-reactive and shows good
compactability. Its main limitation is that some people
have intolerance to lactose.
Other sugars or sugar alcohols, such as glucose, sucrose,
sorbitol and mannitol, have been used as alternative
fillers to lactose, primarily in lozenges or chewable
tablets because of their pleasant taste. Mannitol has a
negative heat of solution and imparts a cooling
sensation when sucked or chewed.
Celluloses are biocompatible, chemically inert and have
good tablet-forming and disintegrating properties. They
are therefore also used as dry binders and disintegrants
in tablets. The most common type of cellulose powder
used in tablet formulation is microcrystalline cellulose.
Starch
Starch is a polysaccharide which is used as a diluent
(and also as a binder and disintegrant) in tablet
formulations. A pregelatinised grade is also available in
which the granules of starch have been physically and
chemically modified to produce a free-flowing powder.
Dibasic calcium phosphate is a commonly used diluent
in tablet formulations. It is a basic excipient and may
therefore chemically interact with acidic components in
the presence of moisture. It has excellent flow and
compression properties.

Binders
Binders are predominantly (but not exclusively)
polymeric components that are employed in the
production of tablets by the wet granulation method of
manufacture. In this role, binders are either added as a
solution or as a solid into the powder mix.

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Binders are included in the formulation at relatively low concentrations, typically 2–10% by weight.
Common traditional solution binders are starch, sucrose and gelatin. More commonly used binders today,
with improved adhesive properties, are polymers such as polyvinylpyrrolidone and cellulose derivatives
(In particular hydroxyl propyl methyl cellulose HPMC). Examples of dry binders are microcrystalline
cellulose and cross-linked polyvinylpyrrolidone.

Matrix Former
In order to control the release of the drug from the tablet, i.e. to speed up or to slow down its release rate,
the drug may be dispersed in a matrix formed by an excipient or a combination of excipients. This type of
excipient may thus be referred to as a matrix former. An alternative term is base, a term used in the
European Pharmacopoeia and there it is defined as ‘the carrier, composed of one or more excipients, for the
active substance(s) in semi-solid and solid preparations’. The matrix former is often a polymer or a lipid and
may constitute a significant fraction of the total tablet weight. When the objective is to increase drug
dissolution, the matrix former can be a water-soluble substance or a lipid and the drug is dissolved or
suspended as fine particles in the matrix. An example of a water-soluble matrix former is poly ethylene
glycol (PEG). When the objective is to prolong the drug release, the matrix former can be either an insoluble
substance (a polymer or a lipid) or a substance that forms a gel in contact with water. The drug is normally
dispersed in particulate form in the matrix. A common gel-forming substance in tablets is hydroxy propyl
methyl cellulose (HPMC).

Disintegrants
Disintegrants are employed in tablet formulations to facilitate the breakdown of the tablet into granules
upon entry into the stomach. If the formulated tablet is hydrophobic and/or it has been manufactured using
a high compression force, the rate of water uptake into, and hence disintegration of, the tablet will be
unacceptably low. In these situations disintegrants are an essential formulation component, enabling tablet
disintegration to occur within the specifications defined in the various pharmacopoeias (typically
disintegration of conventional tablets must occur within 15 minutes).
There are several mechanisms by which disintegrants elicit their effect:
■ Disintegrants may increase the porosity and wettability of the compressed tablet matrix. In so doing
gastrointestinal fluids may readily penetrate the tablet matrix and thereby enable tablet breakdown to
occur. In this approach it is necessary for the disintegrant to be homogeneously dispersed throughout the
tablet matrix (requiring concentrations between 5 and 20% w/w). Examples of disintegrants that operate in
this fashion include: starch – MCC – sodium starch glycolate.
■ Disintegrants may operate by swelling in the presence of aqueous fluids, thereby expediting tablet
disintegration due to the increase in the internal pressure within the tablet matrix. Disintegrants in this
category are typically hydrophilic polymers. To operate effectively it is important that the incorporated
disintegrant does not cause a significant increase in viscosity, thereby decreasing the diffusion of
gastrointestinal fluids into the tablet matrix. Examples of excipients that facilitate tablet disintegration by
swelling in the presence of aqueous fluids include: sodium starch glycolate– croscarmellose sodium –
crospovidone – pregelatinised starch
■ Tablet disintegration may also be mediated by the production of gas whenever the tablet contacts aqueous
fluids. This is the mechanism of disintegration of effervescent tablets.

Lubricants
The function of the lubricant is to ensure that tablet formation and ejection can occur with low friction
between the solid and the die wall. High friction during tableting can cause a series of problems, including
inadequate tablet quality (capping or even fragmentation of tablets during ejection and vertical scratches on
tablet edges called pitting). Lubricants are thus included in almost all tablet formulations.
The most effective of the lubricants are stearic acid or stearic acid salts, such as magnesium stearate.
Magnesium stearate has become the most widely used lubricant owing to its superior lubrication properties.
The stearic acid salts are normally used at low concentrations (<1% by weight).
Besides reducing friction, lubricants may cause undesirable changes in the properties of the tablet. The
presence of a lubricant in a powder is thought to interfere in a deleterious way with the bonding between
the particles during compaction, thus reducing tablet strength. Because many lubricants are hydrophobic,
tablet disintegration and dissolution are often retarded by the addition of a lubricant.

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Glidants
The role of the glidant is to improve the flowability of the powder. Glidants are used in formulations for
direct compaction but are often also added to granules before tableting to ensure that sufficient flowability
of the tablet mass is achieved for high production speeds.
Traditionally, talc has been used as a glidant in tablet formulations, in concentrations of about 1–2% by
weight. Today, the most commonly used glidant is probably colloidal silica, added in very low proportions
(About 0.2% by weight). Because the silica particles are very small they adhere to the particle surfaces of the
other ingredients and improve flow by reducing inter-particulate friction.
Glidants are typically hydrophobic and therefore care should be taken to ensure that the concentration of
glidants used in the formulation does not (in a similar fashion to lubricants) adversely affect tablet
disintegration and drug dissolution.
Magnesium stearate, normally used as a lubricant, can also promote powder flow at low concentrations.

Antiadherent
The function of an antiadherent is to reduce adhesion between the powder and the punch faces and thus
prevent particles sticking to the punches. Many powders are prone to adhere to the punches, a phenomenon
(known in the industry as sticking or picking) which is affected by the moisture content of the powder. Such
adherence is especially prone to happen if the tablet punches have markings or symbols. Adherence can lead
to a build-up of a thin layer of powder on the punches, which in turn will lead to an uneven and matt tablet
surface with unclear markings or symbols.
Many lubricants, such as magnesium stearate, also have antiadherent properties. However, other substances
with limited ability to reduce friction can also act as antiadherents, such as talc and starch.

Adsorbents
Adsorbents are substances that are capable of sorbing some quantities of fluids in an apparently dry state
and they are used whenever it is required to include a liquid or semisolid component, e.g. a drug or a flavour,
within the tablet formulation. As the production of tablets requires solid components, the liquid/semisolid
constituent is adsorbed on to a solid component which, in many cases, may be one of the other components
in the tablet formulation (e.g. diluent) during mixing. If this approach is not possible, an adsorbent is
specifically included in the formulation.
Microcrystalline cellulose, silica, magnesium oxide/carbonate, kaolin and bentonite are examples of sorbing
substances used in tablets.

Sweetening agents/flavours
Sweetening agents and flavours (in accordance with other dosage forms) are employed to control the taste
and hence the acceptability of tablets. These agents are of particular importance if the conventional tablet
contains a bitter drug (taste-masking can also be achieved by coating the tablet or the drug particles) or,
more importantly, if the tablet is a chewable tablet.
Flavouring agents are often thermo-labile and so cannot be added prior to an operation involving heat. They
are often mixed with the granules as an alcohol solution.

Colourant
Colourants are added to tablets to aid identification and patient compliance. Colouring is often accomplished
during coating but a colourant can also be included in the formulation prior to compaction. In the latter case,
the colourant can be added as an insoluble powder or dissolved in the granulation liquid.
In some formulations the drug is coloured and, when manufactured, may result in the tablet exhibiting a
speckled, and hence, inelegant appearance. To obviate this problem, an appropriate colouring agent is
included in the tablet formulation.

Surface-active agents
Surface-active agents may be incorporated into tablets to improve the wetting properties of hydrophobic
tablets and hence increase the rate of tablet disintegration. In addition, surface-active agents may increase
the aqueous solubility of poorly soluble drugs in the gastrointestinal tract and, as a result, the rate of
dissolution of the active agent will increase. One of the most popular choices of surface-active agent for this
purpose is sodium lauryl sulphate. However, it should be noted that the surface-active agent should not
interact with the therapeutic agent as this may affect the dissolution rate of the drug.

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Manufacture of Tableting Powder
Compressed tablets may be made by three basic methods: wet granulation, dry granulation, and direct
compression. Most powdered medicinal agents require addition of excipients such as diluents, binders,
disintegrants, and lubricants to provide the desired characteristics for tablet manufacture and efficacious
use. One important requirement in tablet manufacture is that the drug mixture flows freely from the hopper
of the tablet press into the dies to enable high-speed compression of the powder mix into tablets.
Granulations of powders provide this free flow. Granulations also increase material density, improving
powder compressibility during tablet formation.

WET GRANULATION Wet granulation is a widely employed method for the production of compressed
tablets. The steps required are (a) weighing and blending the ingredients, (b) preparing a dampened powder
or a damp mass, (c) screening the dampened powder or damp mass into pellets or granules, (d) drying the
granulation, (e) sieving the granulation by dry screening, (f ) adding lubricant and blending, and ( g) forming
tablets by compression.
ALL-IN-ONE GRANULATION METHODS Technologic advances now allow the entire process of granulation
to be completed in a continuous fluid bed process, using a single piece of equipment, the fluid bed granulator

DRY GRANULATION By the dry granulation method, the powder mixture is compacted in large pieces and
subsequently broken down or sized into granules. For this method, either the active ingredient or the diluent
must have cohesive properties. Dry granulation is especially applicable to materials that cannot be prepared
by wet granulation because they degrade in moisture or the elevated temperatures required for drying the
granules.

DIRECT COMPRESSION TABLETING Some granular drugs, like potassium chloride; possess free-flowing
and cohesive properties (compressibility) that enable them to be compressed directly in a tablet machine
without any need of granulation.
For drugs lacking this quality, special pharmaceutical excipients may be used to impart the necessary
qualities for the production of tablets by direct compression. These excipients include fillers, such as spray-
dried lactose, microcrystals of alpha-monohydrate lactose, sucrose–invert sugar–corn starch mixtures,
microcrystalline cellulose, crystalline maltose, and dicalcium phosphate; disintegrating agents, such as direct
compression starch, sodium carboxy methyl starch, cross-linked carboxy methyl cellulose fibers, and cross-
linked polyvinylpyrrolidone; lubricants, such as magnesium stearate and talc; and glidants, such as fumed
silicon dioxide. Such drugs are better suited for tableting by granulation techniques rather than direct
compression.

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| P a g e 11
Tablet tooling:
Tablets are formed in a variety of shapes. The most
common tablet shapes are circular, oval and oblong but
tablets may also have other shapes, such as triangular
or quadratic. From a side-view, tablets may be flat or
convex and with or without bevelled edges. Tablets
may also bear break marks or symbols and other
markings. Break marks (or breaklines) are used to
facilitate breaking of tablets in a controlled way to
ensure reproducible doses. Markings are used to
facilitate identification of a preparation and are of two
types: embossed and debossed. Debossed markings are
indented into the tablet and embossed markings are
raised on the tablet surface.

Tablet Coating
At the start of this chapter a description of the various
types of commercially available tablets was provided.
The reader will have observed that tablets are often
formulated with an external coating. A summary of
the rationale for tablet coatings is provided below:
■ to protect the drug from degradation in the stomach (an enteric coating)
■ to prevent drug-induced irritation at a specific site within the gastrointestinal tract, e.g. the stomach for
non-steroidal anti-inflammatory drugs
■ to provide controlled release of the drug throughout the gastrointestinal tract
■ to target drug release to a specific site in the gastrointestinal tract, e.g. the delivery of drug to the colon for
the treatment of inflammatory conditions
■ to mask the taste of drugs
■ to improve the appearance of the tablet.

General description of tablet coating

The main steps involved in the coating of tablets are as follows:
■ The tablets (or granules) are placed within the coating apparatus and agitated.
■ The coating solution is sprayed on to 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 solution.

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Tablet Testing and Quality Control

1- Content Uniformity
A fundamental quality attribute for all pharmaceutical preparations is the requirement for a constant dose of
drug between individual tablets. In practice, small variations between individual preparations are accepted
and the limits for this variation appear as standards in pharmacopoeias. Traditionally, uniformity of dose or
dose variation between tablets is tested in two separate tests: uniformity of weight (mass) and uniformity of
active ingredient. The test for uniformity of weight is carried out by collecting a sample of tablets from a
batch and determining their individual weights. The average weight of the tablets is then calculated. The
sample complies with the standard if the individual weights do not deviate from the mean more than is
permitted in terms of percentage. If the drug substance forms the greater part of the tablet mass, any weight
variation obviously indicates a variation in the content of active ingredient and compliance with the
standard thus helps to ensure that uniformity of dosage is achieved. However, in the case of potent drugs
which are administered in low doses, the excipients form the greater part of the tablet weight and the
correlation between tablet weight and amount of active ingredient can be poor
The test for uniformity of drug content is carried out by collecting a sample of tablets followed by a
determination of the amount of drug in each. The average drug content is calculated and the content of the
individual tablets should fall within specified limits.

2- Disintegration Test
The drug release process from tablets often includes a step at which the tablet disintegrates into smaller
fragments. In order to assess this, disintegration test methods have been developed and examples of these
can be found in pharmacopoeias. The test is carried out by agitating a given number of tablets in an aqueous
medium at a defined temperature and the time to reach the endpoint of the test is recorded. The preparation
complies with the test if the time to reach this endpoint is below a given limit. The endpoint of the test is the
point at which all visible parts of the tablets have been eliminated from a set of tubes in which the tablets
have been held during agitation. The tubes are closed at the lower end by a screen and the tablet fragments
formed during the disintegration are eliminated from the tubes by passing the screen openings, i.e.
disintegration is considered to be achieved when no tablet fragments remain on the screen (fragments of
coating may however remain).
Tests for disintegration do not normally seek to establish a correlation with in vivo behavior. Thus,
compliance with the specification is no guarantee of an acceptable release and uptake of the drug in vivo and
hence an acceptable clinical effect. However, it is reasonable to assume that a preparation which fails to
comply with the test is unlikely to be efficacious.

3- Dissolution Test
Dissolution testing is the most important way to study, under in vitro conditions, the release of a drug from a
solid dosage form and thus represents an important tool to assess factors that affect the bioavailability of a
drug from a solid preparation. During a dissolution test, the cumulative amount of drug that passes into
solution is measured as a function of time. The test thus describes the overall rate of all the processes
involved in the release of the drug into a bioavailable form.
Dissolution is accomplished by locating the tablet in a chamber containing a flowing dissolution medium. So
that the method is reproducible, all factors that can affect the dissolution process are standardized. This
includes factors that affect the solubility of the substance (i.e. the composition and temperature of the
dissolution medium) and others that affect the dissolution process (such as the concentration of dissolved
substance in, and the flow conditions of, the fluid in the dissolution chamber).
The composition of the dissolution medium might vary between different test situations. Pure water or
water mixed with acids or bases to adjust pH are frequently used. In addition, liquids showing a closer
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resemblance to physiological conditions are also used. These are often referred to as simulated gastric or
intestinal fluids or bio-relevant fluids. Also, other dissolution media might be used, such as solvent mixtures,
if the water solubility of the drug is very low. Finally, dissolution studies may be carried out in water-ethanol
solutions in order to assess the potential effect of intake of alcohol drinks close to the administration of a
tablet.

4- Mechanical strength
The mechanical strength of a tablet is associated with the resistance of the solid specimen to fracturing and
attrition. An acceptable tablet must remain intact during handling at all stages, i.e. during production,
packaging, warehousing, distribution, dispensing and administration by the patient. Thus, an integral part of
the formulation and production of tablets is the determination of their mechanical strength.
The most commonly used methods for strength testing can be subcategorized into two main groups:
attrition resistance methods (friability tests) and fracture resistance methods (hardness tests).

A- Attrition resistance methods (Friability test): The idea behind attrition resistance methods is to mimic
the kind of forces to which a tablet is subjected during handling between its production and its
administration. These are also referred to as friability tests; a friable tablet is one that is liable to erode
mechanically during handling.
During handling, tablets are subjected to stresses from collisions and tablets sliding towards one another
and other solid surfaces, which can result in the removal of particles or particle clusters from the tablet
surface. The result will be a progressive reduction in tablet weight and a change in its appearance. Such
attrition can occur even though the stresses are not high enough to break or fracture the tablet into smaller
pieces.
The most common experimental procedure for determining attrition resistance involves the rotation of
tablets in a cylinder, followed by the determination of weight loss after a given number of rotations. Another
approach is to shake tablets intensively in a jar of similar dimensions to a pack-jar. Normally, weight loss of
less than 1% during a friability test is required. In addition, the tablets should not show capping or cracking
during such testing.

B- Fracture resistance methods (Hardness test): Analysis of the fracture resistance of tablets involves the
application of a load on the tablet and the determination of the force needed to fracture or break the
specimen along its diameter or other axis. In order to obtain a controlled loading during the test, care must
be taken to ensure that the load is applied under defined and reproducible conditions in terms of the type of
load applied (compression, pulling, twisting, etc.) and the loading rate.
In such compression testing, the tablet is placed against a platen (a flat metal plate) and the load is applied
along its diameter by a movable platen. The tablet fails (fractures or breaks) ideally along its diameter, i.e.
parallel to the compression load, in a single fracture into two pieces of similar size and the fracture force is
recorded.
The force needed to fracture a tablet depends on the tablet’s dimensions. An ideal test, however, should
allow comparison between tablets of different sizes or even shapes. This can be accomplished by assessing
the strength of the tablet, i.e. the force needed to fracture the tablet per unit fracture area.

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