Aseel Samaro

Tablets
Definition
Definition according to the BP
Tablets are dosage forms that are circular in shape with
either flat or convex faces and prepared by compressing
the medicament or mixture of medicaments usually with
added substances

Tablets are now the most popular dosage form ( 70% of

all ethical pharmaceutical preparations produced)
Advantages of tablets
1. Production aspect
.Large scale production at lowest cost
.Easiest and cheapest to package and ship
.High stability

2. User aspect (doctor, pharmacist, patient)

.Easy to handle
.Lightest and most compact
.Greatest dose precision and least variability
.Coating can mark unpleasant tastes and improve patient acceptability
Disadvantages of tablets
1. Some drugs resist compression into dense compact

2. Drugs with poor wetting, slow dissolution,

intermediate to large dosages may be difficult or
impossible to formulate & manufacture as tablet that
provide adequate or fill drug bioavailability

3. Bitter taste drugs, drugs with an objectionable odor,

or sensitive to oxygen or moisture may require
.Encapsulation or entrapment prior to compression or
.The tablets require coating
Tableting machine
TYPES OF TABLETS
1. COMPRESSED TABLETS
.In addition to the medicinal agent or agents, compressed tablets
usually contain a number of pharmaceutical adjuncts, including the
following:

.Diluents or fillers: which add the necessary bulk to a formulation to

prepare tablets of the desired size.

.Binders or adhesives: which promote adhesion of the particles of

the formulation, allowing a granulation to be prepared and maintaining
the integrity of the final tablet.
 Disintegrants or disintegrating agents: which promote breakup of the
tablets after administration to smaller particles for ready drug availability.

Antiadherents, glidants, lubricants, or lubricating agents: which

enhance the flow of the material into the tablet dies, minimize wear of the
punches and dies, prevent fill material from sticking to the punches and dies,
and produce tablets with a sheen.

Miscellaneous adjuncts: such as colorants and flavorants.

After compression, tablets may be coated with various materials as described

later. Tablets for oral, buccal, sublingual, or vaginal administration may be
prepared by compression.
MULTIPLY COMPRESSED TABLETS
Multiply compressed
tablets are prepared by
subjecting the fill material
to more than a single
compression.

The result may be a

multiple-layer tablet or a
tablet within a tablet, the
inner tablet being the
core and the outer portion
being the shell. .
 Layered tablets are prepared by initial compaction of a portion of fill
material in a die followed by additional fill material and compression to
form two-layered or three- layered tablets, depending on the number of
separate fills.

Each layer may contain a different medicinal agent, separated for

reasons of:
1. chemical or physical incompatibility
2. staged drug release
3. for the unique appearance of the layered tablet.

.Usually, each portion of fill is a different color to produce a distinctive-

looking tablet.

.In preparation of tablets within tablets, special machines are required to

place the preformed core tablet precisely within the die for application of
surrounding fill material.
SUGARCOATED TABLETS
Compressed tablets may be coated with a colored or an
uncolored sugar layer.

The coating is water soluble and quickly dissolves after

swallowing.

1. The sugarcoat protects the enclosed drug from the

environment and provides a barrier to
objectionable taste or odor.
2. The sugarcoat also enhances the appearance of
the compressed tablet and permits imprinting of
identifying manufacturers information.

.Among the disadvantages to sugarcoating tablets are 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
Film-coated tablets are compressed tablets coated with a thin layer of a
polymer capable of forming a skin-like film.

The film is usually colored and has the advantage over

sugarcoatings in that it is:
1. more durable
2. less bulky
3. less time- consuming to apply.

.By its composition, the coating is designed to rupture and expose the core
tablet at the desired location in the gastrointestinal tract.
GELATIN-COATED
TABLETS

A recent innovation is the gelatin-

coated tablet.

The innovator product, the gelcap, is

a capsule- shaped compressed tablet
that allows the coated product to be
about one-third smaller than a
capsule filled with an equivalent
amount of powder.
ENTERIC-COATED TABLETS
Enteric-coated tablets have delayed-release
features.

They are designed to pass unchanged

through the stomach to the intestines, where
the tablets disintegrate and allow drug
dissolution and absorption and/or effect.

Enteric coatings are employed when the drug

substance:
is destroyed by gastric acid or
is particularly irritating to the gastric mucosa
or
when bypass of the stomach substantially
enhances drug absorption.
BUCCAL AND SUBLINGUAL
TABLETS
Buccal and sublingual tablets are flat, oval tablets
intended to be dissolved in the buccal pouch (buccal
tablets) or beneath the tongue (sublingual tablets) for
absorption through the oral mucosa.
 They enable oral absorption of drugs that are
destroyed by the gastric juice and/or are poorly
absorbed from the gastrointestinal tract.

Buccal tablets are designed to erode slowly,

whereas those for sublingual use (such as
nitroglycerin) dissolve promptly and provide rapid
drug effects.

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, although some
are formulated for systemic absorption.
CHEWABLE TABLETS
Chewable tablets, which have a
smooth, rapid disintegration
when chewed or allowed to
dissolve in the mouth, have a
creamy base, usually of specially
flavored and colored mannitol.

Chewable tablets are especially

useful for administration of large
tablets to children and adults
who have difficulty swallowing
solid dosage forms.
EFFERVESCENT TABLETS
Effervescent tablets are prepared by
compressing granular effervescent
salts that release gas when in
contact with water.

These tablets generally contain

medicinal substances that dissolve
rapidly when added to water.

The bubble action can assist in

breaking up the tablets and
enhancing the dissolution of the
active drug.
MOLDED TABLETS
Certain tablets may be prepared by molding rather than
by compression. The resultant tablets are very soft and
soluble and are designed for rapid dissolution.
TABLET TRITURATES
Tablet triturates are small, usually cylindrical, molded or compressed tablets
containing small amounts of usually potent drugs.

Today, only a few tablet triturate products are available commercially, with
most of these produced by tablet compression.

Since tablet triturates must be readily and completely soluble in water, only
a minimal amount of pressure is applied during their manufacture.

A combination of sucrose and lactose is usually the diluent.

The few tablet triturates that remain are used sublingually, such as
nitroglycerin tablets.

Pharmacists also employ tablet triturates in compounding. For example,

triturates are inserted into capsules or dissolved in liquid to provide accurate
amounts of potent drug substances.
HYPODERMIC TABLETS
Hypodermic tablets are no longer available in the United States.

They were originally used by physicians in extemporaneous preparation of parenteral

solutions.

The required number of tablets was dissolved in a suitable vehicle, sterility attained, and
the injection performed.

The tablets were a convenience, since they could be easily carried in the physicians
medicine bag and injections prepared to meet the needs of the individual patients.

However, the difficulty in achieving sterility and the availability of prefabricated injectable
products, some in disposable syringes, have eliminated the need for hypodermic tablets.
DISPENSING TABLETS
Dispensing tablets are no longer in use.

They might better have been termed compounding

tablets because the pharmacist used them to compound
prescriptions; they were not dispensed as such to the
patient.
IMMEDIATE-RELEASE TABLETS
Immediate-release tablets are designed to disintegrate
and release their medication with no special rate-
controlling features, such as special coatings and other
techniques.
EXTENDED-RELEASE TABLETS
Extended-release tablets (sometimes called controlled-
release tablets) are designed to release their medication
in a predetermined manner over an extended period.
VAGINAL TABLETS
Vaginal tablets, also called vaginal inserts, are uncoated,
bullet-shaped or ovoid tablets inserted into the vagina for
local effects.

They contain :
antibacterials for the treatment of nonspecific vaginitis
caused by Haemophilus vaginalis
antifungals for the treatment of vulvovaginitis candidiasis
caused by Candida albicans and related species.
INSTANTLY DISINTEGRATING OR
DISSOLVING TABLETS
Instant-release tablets (rapidly dissolving tablets, or RDTs) 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

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.
 The original fast-dissolving tablets were molded tablets for
sublingual use.

They generally consisted of active drug and lactose moistened

with an alcoholwater mixture to form a paste.

The tablets were then molded, dried, and packaged.

For use, they were simply placed under the tongue to provide
a rapid onset of action for drugs such as nitroglycerin.

Also, they have been used for drugs that are destroyed in the
gastrointestinal tract, such as testosterone, administered
sublingually for absorption to minimize the first-pass effect.
 These RDTs are more convenient to carry and
administer than an oral liquid.

There are no standards that define an RDT, but one possibility is

dissolution in the mouth within approximately 15 to 30 seconds; anything
slower would not be categorized as rapidly dissolving.

Packaging
They are generally packaged in cards or bubble-type packaging
with each individual tablet in its own cavity.
 Not withstanding these advantages, there are a number
of disadvantages and difficulties associated with
formulating RDTs, including:
drug loading
taste masking
friability
manufacturing costs
stability of the product
 COMPRESSED TABLETS
The physical features of compressed tablets are well known:
Round, oblong or unique in shape
thick or thin
large or small in diameter
flat or convex
unscored or scored in halves, thirds, or quadrants
engraved or imprinted with an identifying symbol and/or code number
coated or uncoated
colored or uncolored
one, two, or three layered.
 Tablet diameters and shapes are determined by the die and
punches used in compression.

The less concave the punches, the flatter the tablets; conversely
The more concave the punches the more convex the resulting
tablets.

Punches with raised impressions produce recessed impressions on the

tablets
Punches with recessed etchings produce tablets with raised
impressions or monograms.

Monograms may be placed on one or on both sides of a tablet,

depending on the punches
QUALITY STANDARDS AND
COMPENDIAL REQUIREMENTS
In addition to the apparent features of tablets, tablets must meet other
physical specifications and quality standards.

These include criteria for:

Weight
Weight variation
Content uniformity
Thickness
Hardness
Disintegration
Dissolution

These factors must be controlled during production (in-process controls)

and verified after the production of each batch to ensure that established
product quality standards are met
1. Tablet Weight and USP Weight Variation
Test
The quantity of fill in the die of a tablet press determines the weight of
the tablet.

The volume of fill is adjusted with the first few tablets to yield the
desired weight and content.

For example, if a tablet is to contain 20 mg of a drug substance and if

100,000 tablets are to be produced, 2,000 g of drug is included in the
formula.

After the addition of the pharmaceutical additives, such as the diluent,

disintegrant, lubricant, and binder, the formulation may weigh 20 kg,
which means that each tablet must weigh 200 mg for 20 mg of drug to
be present
 Thus, the depth of fill in the tablet die must be adjusted to hold a volume of granulation
weighing 200mg.

During production, sample tablets are periodically removed for visual inspection and
automated physical measurement.

The USP contains a test for determination of dosage form uniformity by weight
variation for uncoated tablets.

In the test, 10 tablets are weighed individually and the average weight is calculated.

The tablets are assayed and the content of active ingredient in each of the 10 tablets is
calculated assuming homogeneous drug distribution.
2. Content Uniformity

By the USP method, 10 dosage units are individually assayed for their
content according to the method described in the individual
monograph.

Unless otherwise stated in the 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 standard deviation is less than 6%.

If one or more dosage units do not meet these criteria, additional

tests as prescribed in the USP are required.
3. Tablet Thickness
The thickness of a tablet is determined by:
1. The diameter of the die
2. The amount of fill permitted to enter the die
3. The compaction characteristics of the fill material
4. The force or pressure applied during compression.

.To produce tablets of uniform thickness during and between batch

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

.The degree of pressure affects not only thickness but also hardness of
the tablet; hardness is perhaps the more important criterion since it can
affect disintegration and dissolution.
4. Tablet Hardness and Friability
It is fairly common for a tablet press to exert as little as 3,000 and as much as
40,000lb of force

In production of tablets. Generally, the greater the pressure applied, the harder the
tablets, although the characteristics of the granulation also have a bearing on
hardness.

Certain tablets, such as lozenges and buccal tablets, that are intended to dissolve
slowly are intentionally made hard; other tablets, such as those for immediate drug
release, are made soft.

Tablets should be sufficiently hard to resist breaking during normal

handling and yet soft enough to disintegrate properly after swallowing.
 Special dedicated hardness testers or multifunctional systems are used to
measure the degree of force (in kilograms, pounds, or in arbitrary units)
required to break a tablet.

A force of about 4kg is considered the minimum requirement for a

satisfactory tablet.

A tablets durability: may be determined through the use of a friabilator.

A maximum weight loss of not more than 1% generally is considered

acceptable for most products.
5. Tablet Disintegration
For the medicinal agent in a tablet to become fully available for absorption,
the tablet must first disintegrate and discharge the drug to the body fluids
for dissolution.

Tablet disintegration also is important for tablets containing medicinal

agents (such as antacids and antidiarrheals) that are not intended to be
absorbed but rather to act locally within the gastrointestinal tract.

In these instances, tablet disintegration provides drug particles with an

increased surface area for activity within the gastrointestinal tract.

All USP tablets must pass a test for disintegration, which is conducted in
vitro using a testing apparatus.

The apparatus consists of a basket and rack assembly containing six open-
ended transparent tubes of USP-specified dimensions, held vertically upon a
10-mesh stainless steel wire screen.
 Tablets must disintegrate within the times set in the individual monograph, usually 30
minutes, but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for
buccal tablets.

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 tested in
simulated gastric fluid for 1 hour, after which no sign of disintegration, cracking, or
softening must be seen.

They are then actively immersed in the simulated intestinal fluid for the time stated in the
individual monograph, during which time the tablets disintegrate completely for a positive
test.
6. Tablet Dissolution
In vitro dissolution testing of solid dosage forms is important
for a number of reasons :

It guides formulation and product development toward

product optimization.

Dissolution studies in the early stages of a products

development allow differentiation between formulations and
correlations identified with in vivo bioavailability data.

Consistent in vitro dissolution testing ensures

bioequivalence from batch to batch.
 The goal of in vitro dissolution testing is to provide insofar as is possible a reasonable
prediction of or correlation with the products in vivo bioavailability.

The system relates combinations of a drugs solubility (high or low) and its intestinal permeability
(high or low) as a possible basis for predicting the likelihood of achieving a successful in vivoin
vitro correlation (IVIVC).
 Using this system, drugs are placed into one of four categories as follows:

1. Category I drug (high-solubility and high-permeability)

2. Category II drug, dissolution may be the rate-limiting step for absorption, and an
IVIVC may be expected. - dissolution rate is slower than the rate of gastric emptying -

3. Category III drug (In the case of a high-solubility and low- permeability ), permeability
is the rate-controlling step, and only a limited IVIVC may be possible.

4. Category IV drug (low solubility and low permeability) significant problems are
likely for oral drug delivery
 Tablet disintegration is the important first step to the dissolution of the drug in a tablet.

A number of formulation and manufacturing factors can affect the disintegration

and dissolution of a tablet, including
1. particle size of the drug substance
2. solubility and hygroscopicity of the formulation
3. type and concentration of the disintegrant
4. binder
5. lubricant
6. manufacturing method
7. particularly the compactness of the granulation
8. compression force used in tableting
9. any in-process variables
COMPRESSED TABLET MANUFACTURE
Compressed tablets may be made by three basic methods:
wet granulation
dry granulation
direct compression

Most powdered medicinal agents require addition of excipients such as:

diluents
binders
disintegrants
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.
Reasons for Granulation
1. To avoid powder segregation

2. To enhance the flow of powder

3. Granules have higher porosity than powders

4. To improve the compressibility of powders.

5. Avoid dustiness , The granulation of toxic materials will reduce the hazard of generation of toxic dust,
which may arise during the handling of the powders.

6. Materials, which are slightly hygroscope, may adhere & form a cake if stored as a powder.

7. Granules, being denser than the parent powder mix, occupy less volume per unit weight.
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) sizing the granulation by dry screening
(f) adding lubricant and blending
(g) forming tablets by compression.
Weighing and Blending
Specified quantities of active ingredient, diluent or filler, and disintegrating agent
are mixed by mechanical powder blender or mixer until uniform.
Fillers include:
1. lactose
2. microcrystalline cellulose
3. starch
4. powdered sucrose
5. calcium phosphate.

The choice of filler usually is based on:

6. the experience of the manufacturer with the material
7. its relative cost
8. its compatibility with the other formulation ingredients.
EXAMPLE
For example, calcium salts must not be used as fillers with
tetracycline antibiotics because of an interaction between the two
agents that results in reduced tetracycline absorption from the
gastrointestinal tract.

Among the fillers most preferred are:

lactose, because of its solubility and compatibility,
microcrystalline cellulose, because of its easy compaction,
compatibility, and consistent uniformity of supply
 Disintegrating agents include:
1. croscarmellose
2. corn and potato starches
3. sodium starch glycolate
4. sodium carboxymethylcellulose
5. polyvinylpyrroli-done (PVP)
6. crospovidone
7. cation exchange resins
8. alginic acid
9. other materials that swell or expand on exposure to moisture and effect the
rupture or breakup of the tablet in the gastrointestinal tract.
Croscarmellose (2%) and sodium starch glycolate (5%) are often preferred because of
their:
high water uptake
rapid action.

One commercial brand of sodium starch glycolate is reported to swell up to 300% of its
volume in water

When starch is employed, 5% to 10% is usually suitable, but up to about 20% may be
used to promote more rapid tablet disintegration.

The total amount of disintegrant used is not always added in preparing the granulation.
Preparing the Damp Mass
A liquid binder is added to the powder mixture to
facilitate adhesion of the powder particles.

A good binder results in appropriate tablet hardness and

does not hinder the release of the drug from the tablet.
Among binding agents:
solutions of povidone, an aqueous preparation of cornstarch (10% to 20%)
glucose solution (25% to 50%)
molasses
methylcellulose (3%)
carboxymethyl- cellulose
microcrystalline cellulose.

If the drug substance is adversely affected by an aqueous binder, a

nonaqueous solution, or dry binder, may be used.
The amount of binding agent used is part of the
operators art; however, the resulting binderpowder
mixture should compact when squeezed in the hand.

The binding agent contributes to adhesion of the

granules to one another and maintains the integrity of
the tablet after compression.
 Overwetting can result in granules that are too hard
for proper tablet formation
Underwetting can result in tablets that are too soft
and tend to crumble.

When desired, a colorant or flavorant may be added to

the binding agent to prepare a granulation with an
added feature.
Screening the Damp Mass into
Pellets or Granules
The dampened powder granules are screened or the wet mass
is pressed through a screen (usually 6 or 8 mesh) to prepare
the granules.

This may be done by hand or with special equipment that

prepares the granules by extrusion through perforations in the
apparatus.

The resultant granules are spread evenly on large lined trays

and dried to consistent weight or constant moisture content.
Drying the Granulation
Granules may be dried
in thermostatically
cotrolled ovens that
constantly record the
time, temperature, and
humidity.
Sizing the Granulation by Dry
Screening
After drying, the granules are passed through a screen of a smaller mesh than that used to
prepare the original granulation.

The degree to which the granules are reduced depends on the size of the punches to be used.

In general, the smaller the tablet to be produced, the smaller the granules.

Screens of 12- to 20-mesh size are generally used for this purpose.

Sizing of the granules is necessary so that the die cavities for tablet compression may be
completely and rapidly filled by the free-flowing granulation.

Voids or air spaces left by too large a granulation result in the production of uneven
tablets.
Adding Lubrication and Blending
After dry screening, a dry lubricant is dusted over the spread-out
granulation through a fine- mesh screen.

Lubricants contribute to the preparation of compressed tablets in several

ways:
1. They improve the flow of the granulation in the hopper to the die cavity.
2. They prevent adhesion of the tablet formulation to the punches and dies
during compression.
3. They reduce friction between the tablet and the die wall during the
ejection of the tablet from the machine.
4. They give a sheen to the finished tablet
 Among the more commonly used lubricants are:
magnesium stearate
calcium stearate
stearic acid
talc,
sodium stearyl fumarate.

Magnesium stearate is most used.

The quantity of lubricant used varies from one operation to another but
usually ranges from about 0.1% to 5% of the weight of the granulation.
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.
The fluid bed granulator performs the following steps:
(a) preblending the formulation powder, including active
ingredients, fillers, and disintegrants, in a bed with
fluidized air
(b) granulating the mixture by spraying onto the fluidized
powder bed, a suitable liquid binder, such as an aqueous
solution of acacia, hydroxypropyl cellulose, or povidone
(c) drying the granulated product to the desired moisture
content.
 Another method, microwave vacuum processing, also allows the powders to be:
mixed
wetted
agglomerated
dried within the confines of a single piece of equipment.

o The wet mass is dried by gentle mixing, vacuum, and microwave.

o The use of the microwave reduces the drying time considerably, often by one fourth.

o The total batch production time is usually in the range of 90 minutes.

o After adding lubricants and screening, the batch is ready for tablet formation or capsule filling.
Advantages of wet granulation
Advantages
Reduced segregation of formulation components during
storage and/or processing

Useful technique for the manufacture of tablets containing

low and or high concentrations of therapeutic agent

Employs conventional excipients and therefore is not

dependent on the inclusion of special grades of excipients
Disadvantages of wet granulation

Disadvantages
1. Often several processing steps are required
2. Solvents are required in the process: this leads to a
number of concerns:
.Drug degradation may occur in the presence of the
solvent
.The drug may be soluble in the granulation fluid
.Heat is required to remove the solvent
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.
Slugging
After weighing and mixing the ingredients, the powder mixture is slugged,
or compressed, into large flat tablets or pellets about 1 inch in diameter.

The slugs are broken up by hand or by a mill and passed through a screen
of desired mesh for sizing.

Lubricant is added in the usual manner, and tablets are prepared by

compression.

Aspirin, which is hydrolyzed on exposure to moisture, may be prepared

into tablets after slugging.
Roller Compaction
Instead of slugging, powder compactors may be used to increase the density of
a powder by pressing it between rollers at 1 to 6 tons of pressure.

The compacted material is broken up, sized, and lubricated, and tablets are
prepared by compression in the usual manner.

The roller compaction method is often preferred to slugging.

Binding agents used in roller compaction formulations include

Methylcellulose
hydroxy methylcellulose (6% to 12%),
which can produce good tablet hardness and friability.
Advantages of dry granulation

Advantages of dry granulation

1. These methods are not generally associated
with alterations in drug morphology during
processing.
2. No heat or solvents are required.
Disadvantages of dry granulation
1. Specialist equipment is required for granulation by roller compaction.

2. Segregation of components may occur mixing.

3. There may be issues regarding powder flow.

4. The final tablets produced by dry granulation tend to be softer than those
produced by wet granulation

5. Slugging and roller compaction lead to the generation of considerable dust

DIRECT COMPRESSION TABLETING
Some granular chemicals, like potassium chloride, possess free-
flowing and cohesive properties that enable them to be compressed
directly in a tablet machine without any need of granulation.

For chemicals 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
sucroseinvert sugarcorn starch mixtures
microcrystalline cellulose
crystalline maltose
dicalcium phosphate
Disintegrating agents, such as:
direct compression starch
sodium carboxymethyl starch
cross-linked carboxymethylcellulose fibers
cross-linked polyvinylpyrrolidone

lubricants, such as:

magnesium stearate
talc

Glidants, such as
fumed silicon dioxide
Advantages and disadvantages of
direct compression
Advantages:
1. Low labour input
2. A dry process
3. Fewest processing steps

Disadvantages:
4. Stratification (layers) may occur due to differences in particle size and bulk density which
results poor content uniformity.

5. A large dose drug may cause problem in direct compression. It requires diluents. The tablet
becomes large in size which is difficult to swallow and also costly.

6. During handling of dry materials static charge may form which may present uniform distribution
of drug.

7. Direct compression diluent may interact with the drug. For example, amine drug with Lactose
produce discoloration of tablet
 WET GRANULATION DRY GRANULATION DIRECT
COMPRESSION
1. Milling and mixing of 1. Milling and mixing of 1. Milling and
drugs and excipients drugs and excipients mixing of drugs
and excipients
2 .Preparation of binder 2. Compression into 2. Compression of
solution slugs or roll compaction tablet
3. Wet massing by 3. Milling and screening
addition of binder solution of slugs and compacted
or granulating solvent powder
4. Screening of wet mass 4. Mixing with
disintegrant/lubricant
5. Drying of the wet 5. Compression of tablet
granules
6. Screening of dry
granules
7. Blending with
disintegrant / lubricant
and
Compression process

Filling: By gravitational flow (or mechanical conveyors) 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

Ejection: 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.
Tablet compression machine
1. Hopper for holding and feeding granulation to be compressed

2. Dies that define the size and shape of the tablet

3. Punches for compressing the granulation within the dies

4. Cam tracks for guiding the movement of the punches

5. Feeding mechanisms for moving granulation from the hopper

into the die

6. Tablet ejector
 Tablets Defects
Laminatio
n
Cappi
Sticking &
ng
Picking

Chippi
ng

Double Impressions Splitting

Erosio
n

Hardness Thicknes
Black
variation s
Spots
variation
 1. Capping

CAPPING happened when the upper

or lower segment of the tablet
separates horizontally, either
partially or completely from the
main body of a tablet and comes off
as a cap, during ejection from the
tablet press, or during handling or
other process.

Reason: Capping is usually due

to the
1. Air entrapment
2. Large amount of fines in the
2. Lamination
Lamination is the separation of a tablet
into two or more distinct horizontal
layers.

Reason:
1. Air - entrapment during compression
2. Too much of hydrophobic lubricant e.g.: Magnesium-stearate
3. Rapid decompression
3. Sticking & Picking
Sticking is one of the most common problems of tablet making. It occurs
when granules attach and stick to the faces of the punches instead of
locking together to create a uniform tablet.

Picking is a specific type of sticking in which particles stick within the

letters and logos that are embossed or debossed on the faces of the
compression tooling
Weight variation ---- hardness
thickness- dissolution
moisture content
particle size distribution
Bad quality of the punches surface not
smooth
Air entrapment
Tablet Dedusting
To remove traces of loose powder adhering to tablets
following compression, the tablets are conveyed directly
from the tableting machine to a deduster.

The compressed tablets may then be coated.

Tablet coating
 Tablet coating
Coated tablets are defined as tablets
covered with one or more layers of mixture of
various substances.

Coating may also contain active ingredient.

Substances used for coating are usually

applied as solution or suspension under
conditions where vehicle evaporates.
Objectives of Coating/why coating

1. Reduce influence of atmosphere

2. Mask: taste odor & color of drug
3. Control or Modify drug Release: CR, SR .
4. Protect drug against GI environment : Enteric
coating
5. Avoid irritation of esophagus and stomach
6. Incompatibility: Drug & drug
7. Improve elegance : color imprinting & patient
acceptance
8. Increases the mechanical strength of the core
tablet
Types of coating processes
The main types are used in the pharmaceutical
industry today
Functional
coating
Coating Non Functional
coating

- Sugar coating Compression 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.
Sugar coating
Description of tablets: Smooth, rounded and polished to
a high gloss.
Process: Multistage process involving 6 separate
operations
Sugar coating
Sealing tablet core: application of a water impermeable polymer such
as Shellac, cellulose acetate phthalate and polyvinyl acetate
phthalate, which protects the core from moisture, increasing its shelf
life.

Sub coating After the tablets are waterproofed if needed, three to five
subcoats of a sugar-based syrup are applied. This bonds the sugar coating to
the tab- let and provides rounding. The sucrose and water syrup also contains
gelatin, acacia, or PVP to enhance coating.

Smoothing process -remove rough layers formed in step 2 with the

application of sucrose syrup. This syrup is sucrose based, with or without
additional com- ponents such as starch and calcium carbonate.
Sugar coating
Colouring - for aesthetic purposes often
titanium based pigments are included.

Polishing - effectively polished to give

characteristic shine, commonly using
beeswax, carnauba wax.

Printing -permanent ink for characterization

 Film coating
Coating tablets, capsules, or pellets by
surrounding them with a thin layer of
polymeric material.
Process: Single stage process, which involves
spraying a coating
The solution or suspension is sprayed to
a rotating tablet bed followed by drying,
which facilitates the removal of the
solvent leaving behind the deposition of
thin film of coating materials around each
tablet
Film coating

Film coating contains the following;

1. Film forming Polymer
2. Solvent
3. Plasticizer
4. Colourant
Film forming Polymer
 Plasticizer

LOW MOLECULAR WEIGHT ORGANIC MOLECULES,

CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A
POLYMER
- Better mechanical properties
Resistance to deformation
Flexible, elastic films (high modulus of
elasticity)
Continuous film
 Solvent

Solvent

organic Product Stability P. Water

Environmental
Safety
Financial
Solvent residues
 Film-coating solutions may be nonaqueous or aqueous.

The nonaqueous solutions contain the following types of materials to provide

the desired coating to the tablets:

1. A film former capable of producing smooth, thin films reproducible under

conventional coating conditions and applicable to a variety of tablet shapes.
Example: cellulose acetate phthalate.

2. An alloying substance providing water solubility or permeability to the film

to ensure penetration by body fluids and therapeutic availability of the drug.
Example: polyethylene glycol.
3. A plasticizer to produce flexibility and elasticity of the coating and thus provide
durability. Example: castor oil.

4. A surfactant to enhance spreadability of the film during application. Example:

polyoxyethylene sorbitan derivatives.

5. Opaquants and colorants to make the appearance of the coated tablets handsome
and distinctive. Examples: Opaquant, titanium dioxide; colorant, FD&C or D&C dyes.

6. Sweeteners, flavors, and aromas to enhance the acceptability of the tablet by the
patient. Examples: sweeteners, saccharin; flavors and aromas, vanillin.

7. A glossant to provide luster to the tablets without a separate polishing operation.

Example: beeswax.

8. A volatile solvent to allow the spread of the other components over the tablets
while allowing rapid evaporation to permit an effective yet speedy operation.
Example: alcohol mixed with acetone.
 One commercial water-based colloidal coating dispersion called
Aquacoat (FMC Corporation) contains a 30% ethyl cellulose
pseudolatex.

Pseudolatex dispersions have a high solids content for greater coating

ability and a relatively low viscosity.

The low viscosity allows less water to be used in the coating dispersion,
requiring less evaporation and reducing the likelihood that water will
interfere with tablet formulation.

In addition, the low viscosity permits greater coat penetration into the
crevices of monogrammed or scored tablets.

A plasticizer may be added to assist in the production of a dense,

relatively impermeable film with high gloss and mechanical strength.
 A typical aqueous film-coating formulation contains the following:
1. Film-forming polymer (7% to 18%). Examples: cellulose ether polymers such
as hydroxypropyl methylcellulose, hydroxypropyl cellulose, and
methylcellulose.

2. Plasticizer (0.5% to 2.0%). Examples: glycerin, propylene glycol, polyethylene

glycol, diethyl phthalate, and dibutyl subacetate.

3. Colorant and opacifier (2.5% to 8%). Examples: FD&C or D&C lakes and iron
oxide pigments.

4. Vehicle (water, to make 100%).

Film coating Sugar coating
Film coating Sugar coating
Tablet appearance Tablet appearance
Retains shape of original Rounded with high degree of
core polish
Small weight increase of Larger weight increase 30-100 %
2-10 % due to coating due to coating material
material Logo or break lines are
logo or break lines Impossible
possible
Process Wait & size variation within the
Process
No Wait & size variation
Can be automated batch or from batch to batch
Difficult to automated
Easy training operation Considerable training operation
Single stage process Multi stage process
Less Time More time
Easily adaptable for controlled Not able to be used for controlled
release allows for functional Release
coatings.
 Problems of Film Coating
PICKING/ STICKING: small
holes pulled in film or small
amount of the film flaking from
the tablet surface

PEELING: the coating peels

away from the tablet surface or
large amount of the film
flaking from the tablet surface
 Problems of Film Coating
Roughness or orange peel :
film not smooth

Twinning: two or more tablets that

stick together. Common problem
with flat or capsule shaped tablets
 Problems of Film Coating

CRACKING: Torn or cracked films

CORE EROSION: loss of

material from tablet surface
 Problems of Film Coating
Color Variation or mottling

LOGO BRIDGING: the

coating fills in the logo on
the tablets
Functional coatings
Functional coatings are coatings, which perform a
pharmaceutical function
Enteric coating
Controlled release coating
 ENTERIC COATING
The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH
sensitive polymer, which swell or solubilize in response to an increase in pH
to release the drug.

Aims of Enteric protection:

1. Protection of active ingredients, from the
acidic environment of the stomach.

2. Protection from local irritation of the

stomach mucosa.

3. Release of active ingredient in specific

target area within gastrointestinal tract.
Among the materials used in enteric coatings are:
1. Pharmaceutical shellac
2. Hydroxypropyl methylcellulose phthalate
3. Polyvinyl acetate phthalate
4. Diethyl phthalate
5. Cellulose acetate phthalate.
FLUID BED COATER
 Press coating

Press coating process involves compaction of coating

material around a preformed core

for creating modified-released

products involves the compaction of
granular materials around preformed
tablet core using specially designed
tableting equipment. Compression
coating is a dry process
COMPRESSION COATING

Compared to sugarcoating using pans, compression

coating is more uniform and uses less coating material,
resulting in tablets that are lighter, smaller, and easier
to swallow and less expensive to package and ship.
CHANGES ON SOLID DOSAGE FORM
Starting materials
Manufacturing process
PACKAGING AND STORING TABLETS
Tablets are stored in tight containers, in places of
low humidity, and protected from extremes in
temperature.
 Products that are prone to
decomposition by moisture generally
are packaged with a desiccant packet.

Drugs that are adversely affected by

light are packaged in light-resistant
containers.

With a few exceptions, tablets that are

properly stored will remain stable for
several years or more.
Upon aging
Hardness - The increase in tablet hardness can
frequently be attributed to the increased adhesion of
the binding agent and other formulative components
within the tablet
 In tablets containing volatile drugs, such as nitroglycerin, the drug
may migrate between tablets in the container, resulting in a lack of
uniformity among the tablets.

Also, packing materials, such as cotton and rayon, in contact with

nitroglycerin tablets may absorb varying amounts of nitroglycerin,
reducing potency of the tablets.

The USP directs that nitroglycerin tablets be preserved in tight

containers, preferably of glass, at controlled room
temperature.
Also, migration within tablets can occur resulting in
unequal distribution within a single tablet; this can be
problematic if the tablet is scored and designed to be
broken in half where the two halves may not contain equal
portions of the drug.

Storage of a container next to a heat source may

result in greater loss or movement of the volatile
drug in the portion of the bottle closest to the heat.
 The USP further directs that nitroglycerin tablets be
dispensed in the original unopened container, labeled
with the following statement directed to the patient.
Warning: to prevent loss of potency, keep these tablets
in the original container or in a supplemental
nitroglycerin container specifically labeled as being
suitable for nitroglycerin tablets. Close tightly
immediately after use (4).
 OTHER SOLID DOSAGE FORMS FOR ORAL
ADMINISTRATION
LOZENGES
LOLLIPOPS
Chewable tablets
Chewable tablets are pleasant-tasting tablets formulated to
disintegrate smoothly in the mouth with or without chewing.

They are prepared by wet granulation and compression, using

only minimal degrees of pressure to produce a soft tablet.

Generally, chewable tablets do not contain disintegrants, so

patients must be counseled to chew the tablets thoroughly
and not swallow them whole.
 Mannitol, a white crystalline hexahydric alcohol, is used as the excipient
in most chewable tablets.

Mannitol is about 70% as sweet as sucrose, with a cool feel in the mouth.

Mannitol accounts for 50% or more of the weight of many chewable

tablet formulations.

Sometimes other sweetening agents, such as:

sorbitol
lactose
dextrose
crystalline maltose
glucose
may be substituted for part or all of the mannitol.
Xylitol may be used in the preparation of sugar- free chewable tablets.
Among the types of products prepared as chewable tablets are:
1. antacids (e.g., calcium carbonate)
2. antibiotics (e.g., erythromycin)
3. anti-infective agents (e.g., didanosine)
4. anticonvulsants (e.g., carbamazepine)
5. vasodilators (e.g., isosorbide dinitrate)
6. analgesics (e.g., acetaminophen)
7. various vitamins
8. Cold allergy combination tablets.
The following is a formula for a typical
chewable antacid tablet
Aluminum hydroxide 325.0mg

Mannitol 812.0mg

Sodium saccharin 0.4mg

Sorbitol (10% w/v solution) 32.5mg

Magnesium stearate 25.0mg

Mint flavor concentrate 4.0mg