Tablet, Granules, Capsules PDF

Pharmaceutics – II (Dosage Form Science):
CAPSULES DOSAGE FORM

Definition:
 Encapsulation refers to a range of techniques used to enclose medicines in a relatively stable
shell known as a capsule.
 Capsules are dosage form containing unit doses of drugs enclosed in a soluble shell of gelatin,
starch or similar material and intended to be swallowed whole orally.
Introduction:
 Capsules equal the tablets in their popularity and usage.
 They are convenient means of dispensing a variety of solids, semi-solids and liquids.
 All capsules basically consist of soluble shells of a material like gelatin. The solid substances are
dispensed in hard capsules for dispensation of liquids and semi-solids soft capsules are preferred.
 Capsules are generally employed for enclosing materials meant for oral administration and are
swallowed as a whole.
 Nowadays some capsules are administered through rectum or vagina and are useful substitutes
for the more conventional types of suppositories based on oleaginous or water soluble bases.
 Soft capsules can also be employed for enclosing single application of eye ointments. Here the
capsules have to be pricked with needle and the contained ointment transferred to ophthalmic
cavity by application of slight pressure.
 Capsules afford a tasteless, odorless enclosure, convenient for administration of variety of
medicaments, which are otherwise difficult to administer.
 However, aqueous or hydroalcoholic liquids cannot be enclosed in capsules because they
dissolve gelatin.
Danger:
 Capsules should not be used for packaging of highly water soluble materials such as ammonium
chloride, potassium bromide, potassium chloride etc., because sudden release of such compounds
can cause irritation.
 It is also not advisable to use capsules for very deliquescent (to become liquid) or efflorescent
(loss of water of hydration) materials. Deliquescent substances may draw up moisture from the
capsule shell rendering it brittle. The efflorescent materials may cause softening of the capsules.
Types of Capsule:
Prepared by: Muhammad Muneeb
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There are two types of capsules available
1. Hard Gelatin Capsules

2. Soft Gelatin Capsules
HARD GELATIN CAPSULE

o This type is also referred as the dry filled capsule, which consists of two sections, one slipping
over the other, thus completely surrounding the drug formulation.
o These are formed from gelatin containing sugar and water in appropriate proportions.
o Hard gelatin capsules are manufactured in two sections:-
o The capsule body
o Shorter cap
o The two parts overlap when joined, with the cap fitting snugly-over opened of capsule body.
Types of Hard Gelatin Capsules:

Hard gelatin capsules are of following types:
 Snap Fit
 Coni Snap
 Coni Snap Supro
All these types have locking grooves, generally, two, Snap Fit Capsules are bearing the
disadvantage of slitting and denting due to contact b/c the rim of capsule body is straight.
Capsule Shell:
The shell of hard gelatin capsules basically consists of gelatin, plasticizers and water. Modern
day shells may, in addition, consist of preservatives, colours, opacifying agents, flavours, sugars, acids,
enteric materials etc. The gelatin is marketed in a large number of varieties and a specific quality and
gelatin having specified gel strength, viscosity, iron content etc. should be selected for capsules.
The variations in gelatin properties arise because of changes in molecular weights and methods
followed in conversion into gelatin.
The average molecular weight of gelatin varies between 20,000 and 2, 00,000. Two popular
grades of gelatin, Pharmagel-A and Pharmagel-B, are acid processed and alkali processed
respectively
For capsule shells generally a mixture derived from pork skin and bones is used. Pork skin
gelatin contributes plasticity while bone gelatin gives firmness. However, in using bone gelatin
its calcium phosphate content should be watched since undue amounts can make capsules hazy.

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One important reason for the exclusive use of gelatin for making hard and soft capsules is its
solubility characteristics in stomach fluids. It absorbs cold water readily, though the rate of
absorption depends upon moisture content of gelatin.
The plasticizers used are glycerin, sorbitol etc. The exact proportions of gelatin and plasticizers
have to be determined on the basis of the use of capsules and their storage conditions.
Preservatives, if included, are generally a mixture of methyl-paraben (4 parts) and propylparaben
(1 part) to the extent of 0.2%.
Flavors, if added, should not exceed 2% and are generally ethyl-vanillin or essential oils. Sugar,
if included, may be up to 5% to give the gelatin shell desirable chewable characteristics.
The capsule shells are nowadays produced on mass scale by sophisticated machinery.
Fundamentally speaking, in every machinery, pairs of pins corresponding to the bodies and the
caps of the capsules are dipped in heated gelatin solutions containing the necessary additives.
The dipping is followed by withdrawal of pins and their rotation a few times to distribute the
solutions evenly. Cold air is simultaneously blown on the rotating pins to firm up the gelatin
shells. These pins are, thereafter, passed though series of kilns with controlled rates of drying.
After drying, the bodies and caps are remove4d from pins by mechanical jaws and are trimmed
to appropriate lengths by rotating blades. Finally the caps are placed on the bodies.
Storage:
The capsules shells should be stored under controlled conditions of temperature and humidity.
The normal moisture content of shell is 10 to 15%. Under conditions of low humidity they may soften
and grow tacky.
Sizing:
 In Canada, starch or cellulose are available in a range of sizes with designations 000, 00, 0E, 0,
1, 2, 3, and 4. The respective volumetric capacities are 1.37ml, 950μl, 770μl, 680μl, 480μl,
360μl, 270μl, and 200μl.
 The shells for human use are marketed in 8 sizes depends upon its density and compressibility.
Normally the shell manufacturers give a guidance of the approximate quantities of selected drugs
that can be contained in different sizes. For instance, data from Parke Davis & Co. with respect
to aspirin is reproduced below: For veterinary use larger capsules Nos. 10, 11 and 12
approximating to capaciti9es of 30, 15 and 7.5 gms. Are also marketed.
Hard Gelatin Capsules for Human Use:

Hard gelatin capsules intended for human are manufactured in eight sizes.
 000 _______ 1000mg

 00 ________ 650mg
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 0 _________ 520mg
 1 _________ 320mg
 2 _________ 260mg
 3 _________ 195mg
 4 _________ 160mg
 5 _________ 97mg
Manufacture:
Some special techniques used in hard gelatin capsule manufacturing are
 Imprinting (a word or company name)

 Sealing or banding (tamper proofing)
 Two-phase filling (to separate incompatible material in same capsule)
 Various coating etc.
HARD GELATIN CAPSULE MANFACTURING STEPS

1. Before capsule manufacturing start, first all raw materials should be released by Quality Control
and all equipment should be validated.
2. First step is make gelatin solution 25-30%: gelatin and hot demineralized water are mixed under
vacuum in Gelatin Melting System.
3. After aging in stainless steel receiving tanks, the gelatin solution is transferred to stainless steel
feed tanks.
4. Dyes, opacifants, preservative and any needed water are added to the gelatin in the feed tanks.
The feed tanks are then used to gravity-feed gelatin into the machine for making capsules.
5. Dipping: At the end of machine is a hopper called a dip pan or pot. This holds a fixed quantity of
gelatin at constant temperature between 45 to 55 C. capsules are formed by dipping the sets of
molds which are at the room temperature, 22 C into this solution.
6. Spinning: The molds are slowly withdrawn from solution and then rotated during their transfer
to upper level of the machine in order to form a film of uniform thickness.
7. Drying: Groups of pin bars are then passed through a series of drying kilns in which large
volume of controlled humidity air are blown over them. When they reach the rear of machine the
bars are transferred back to the lower level and pass through the further drying kilns.
8. Cutting and joining: In the front of machine the dried films are removed from mold, cut to
correct length. The two parts are joined together and the complete capsule delivered from the
machine.
9. Output: The output per machine is about 1 million capsules per day, depending upon the size the
smaller the capsule the higher the output.

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10. Assembling: The assembled capsules are not fully closed at this stage and are in a pre-locked
position which prevent them from falling apart before they reach the filling machine
Materials to be filled:
The materials to be filled in the hard capsules may need formulation to a certain extent and the
following additives may have to be incorporated:
DILUENTS
 The dose of a particular medicament may be enough to fill in a suitable size of the capsule. But
there may also be occasions when it is too small in bulk falling far short of the quantity needed
for smallest available capsule size.
 In such instances one or the other diluents has to be added to bring the medicament up to a
desired bulk. The usual diluents selected are lactose, mannitol, sorbitol, starch etc. The quantities
of diluents are related to the dose of the medicament and the capsule size.
PROTECTIVE SORBENTS
In some cases inclusion of inert materials may be called for to physically separate incompatible
or eutectic substances. Sometimes some inert materials are included to prevent absorption of moisture by
hygroscopic substances. Materials like oxides and carbonates of magnesium or calcium are suitable for
these purposes.
GLIDANTS

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Glidants become essential when the powders are filled by s\automated machinery requiring their
regular flow into the capsule bodies many materials by themselves lack the desired degree of flow and
hence glidants like talcum, stearates etc. are included in suitable amounts.
ANTI-DUSTING COMPOUNDS
 In large scale filling operations dust is a real problem and if allowed to go unchecked, can pose
serious health hazards for the workers. Presence of potent drugs in the dust can cause its
continuous inhalation. Hence, material to be filled in the capsules should include some anti-
dusting components like inert edible oils. The quantities of oils have to be carefully worked out
since excessive amounts can cause the particles to cohese together.
 Although normally only powders are filled but on occasions fixed oils and other liquids, that do
not permeate through gelatin wall, can be filled in the hard capsules. Filling of liquids is done by
the use of calibrated droppers or pipettes. The other materials to be filled in could be plastic
dough like masses rolled into uniform pipes. Before filling pipes are cut into uniform pieces and
put in the capsules. Sometimes potent drugs are filled in the form of small tablets or pellets and
are then covered with inert materials to fill the body. Granular materials can also be conveniently
filled in the capsules.
 Substances which are highly soluble in water lice citric acid, sodium chloride and ammonium
compounds should not be filled in gelatin capsules since they may affect the gelatin shell owing
to abstraction of water from it. Some water soluble substances may also migrate into the gelatin
shell thus reducing potency of the encapsulated substance. Excellent examples were thiamine
HCl and ascorbic acid. Sometimes even poorly water soluble substances like benzocaine migrate
into the shell.
FILLING
Extemporaneous filling of a small number of capsules is possible by spreading the powder to be

filled in on a tile or a sheet of paper and pressing the body of capsule on to it until it is full. Cap is
inserted on the body and the capsule weighed against a tare of empty capsule to get a feel about the drug
amount. It may be necessary to fill in some more or tap out some filled in material in case of variations
in weights beyond permitted limits. On an industrial scale semi automatic or fully automatic equipment
is used for filling. In these operations the caps are removed, bodies filled, caps replaced and filled
capsules ejected. Some machines can fill 15000 to 20000 capsules per hour.
FINISHING
The filled and sealed capsules necessitate a finishing operation before inspection, bottling or
packing in strips/blisters and labeling. The following steps are involved in the finishing process:
SALT POLISHING

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In salt polishing, the capsules are rotated in a coating pan type device along with sodium chloride
granules. Later the capsules and granules are separated by screening on a suitable device. Such a
polishing removes adhering materials from the surfaces of capsules. However, salt polishing should be
done before imprinting, if any, since imprinting may be affected by salt.
CLOTH DUSTING
In this process individual capsules are rubbed with cloth which may or may not contain inert oil.
This removes some remaining materials and also imparts improved gloss.
BRUSHING
In brushing capsules are projected under soft a rotating brush which removes all remaining dust.
This operation must be supplemented by exposure of capsules to regulated vacuum.
INSPECTION
This process is desirable to pick up imperfect and damaged capsules manually or with automated
inspecting systems.
SEALING AND LOCKING
Sealing and locking devices invented by various manufacturers as their novelties are basically
guards against separation of the caps from the bodies during handling, transport etc. However,
incidentally these devices do not permit any tampering of their contents ruling out foul play. Sealing of
the caps on to bodies is possible by moistening the upper part of the body and slipping the cap on.
However, many manufacturers seal capsules by means of a colored band of gelatin placed at the junction
of the body and the cap. More recently some configurations have been developed in the bodies and caps
which enable their mechanical locking. For instance, Snap Fit capsules, marketed by Parke Davis, have
matching interlocking rings on the body and in the cap. Another method suggested is to bring a hot
needle like structure against the cap where it overlies the body to form a sort of spot weld.
Some Modern Uses of Hard Gelatin Capsules:

 Traditionally hard gelatin capsules have been used for enclosure of powders or other solid
substances like granules and pellets.
 Recently pastes and oils have also been filled in hard gelatin capsules.
 To prevent leakage of oily materials either thixotropic substances can be added or the cap and
body joints banded with molten gelatin or sealed with lacquers.
 Incompatible drugs also can be usefully supplied in capsules.
 Multilayer tablets are devices towards this end. But it would be more useful to make small
tablets from each individual drug and encapsulate them all in one capsule.
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 Hard gelatin capsules have also been used for drug delivery in bronchial tract.
 To release the drug the capsule is punctured thereby releasing a fine powder mist which is
inhaled into the lungs along with the breath. Maybe with passage of time some new applications
are developed.
SOFT GELATIN CAPSULES

 “The soft gelatin is a soft, globular, gelatin shell somewhat thicker than that of hard gelatin
capsules. The gelatin plasticized by the addition of glycerin and sorbitol”
 These are prepared from gelatin to which glycerin or a polyhydric alcohol such as sorbitol has
been added to render the gelatin elastic or plastic like.
Introduction:
 Although soft gelatin capsules are nearly a century and a half old, their increased and varied use
is a recent phenomenon.
 As discussed earlier, these capsules can not only be used for packaging of liquid/semisolid
dosage forms, powders etc. but have also been used as substitutes for suppositories and for
containing ear, eye, nose and throat formulations.
 Suggestions have also been made for packaging cosmetics and foods in soft gelatin capsules.
 Their popularity is on the increase. Besides being elegant the capsules are hermetically sealed
and are suitable for drugs liable to volatilization and atmospheric deterioration.
Composition:
The composition of soft gelatin capsule shells is similar to the hard gelatin capsules except that a
larger proportion of plasticizer is incorporated to make them soft and elastic.
Shapes:
These capsules are available in a variety of shapes.
 Spherical
 Round
 Oval
 Oblong
 Elliptical
 Tube shape
Size wise also the range is bigger and capsules of capacities ranging from 0.1 ml to 30 ml are
used.
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Manufacture:
They are not easily prepared except on a large scale with specialized equipments
 Plate process
 Rotary die process
 Reciprocating die process
 Accogel machine
 Soft gelatin capsules are usually prepared, filled and sealed in a continuous process using special
equipment.
 Empty soft gelatin capsules may be prepared and hermetically sealed for filling at a later time.
PLATE PROCESS:
 Soft gelatin capsules may be prepared by plate process using a set of mold to form the capsules.
 By the plate process
 A warm sheet of plain or colored gelatin is placed on the bottom plate of the mold and the
medication containing liquid is evenly
poured on it.
 Then a second sheet of gelatin is
carefully placed on the top of
medication and the top plate of mold
is put into the place.
 Pressure is than applied to the mold to
form, fill and seal the capsules
simultaneously.
 The capsules are removed and washed
with a solvent harmless to the
capsules.
ROTARY DIE PROCESS:

Most soft gelatin capsules are
prepared by rotary die process, a method
developed in 1933 by Robert P. Scherer. By
this method:
 Liquid gelatin flowing from an

overhead tank is formed into two
continuous ribbons by the rotary die

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machine and brought together between twin rotatory dies.
 At the same time, metered fill material is injected between the ribbons precisely at the moment
that dies form pockets of gelatin ribbons.
 These pockets of fill containing gelatin are sealed by pressure and heat and then severed from the
ribbons.
 Use of ribbons of two different colors result in bi-colored capsules.
RECIPROCATING DIE PROCESS

 This process is similar to the rotary process in that ribbons of gelatin are formed used to
encapsulate the fill, but it differs in the actual encapsulating process.
 The gelatin ribbons are fed between a set of vertical dies that continuously open and close to
form rows of pockets in gelatin ribbons.
 These pockets are filled with the medication and are sealed, shaped and cut out of the film as
they progress through the machinery.
 As the capsules are cut from the ribbons, they fall into refrigerated tanks that prevent the capsule
from adhering to one another.
Materials to be filled:
They may be employed to contain:
 Liquids
 Suspensions
 Pasty materials
 Dry powders
Soft gelatin capsules are especially important to contain:-
 Drug solutions
 Liquid drugs
As stated earlier, it is possible to fill liquids, semi-solids as well as solids into soft gelatin
capsules. The liquids that are packaged are generally of the following kinds:
1. Vegetable or aromatic oils, hydrocarbons, ethers, esters, alcohols and organic acids which are
water immiscible;
2. Polyethylene glycols and non-ionic surfactants which are water miscible;
3. Water miscible and relatively non-volatile compounds such as glycerin, propylene glycol (up to
5-10% of total liquid), isopropyl glycol etc.

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Conditions for Filling:
 The liquid combinations for encapsulation in soft gelatin capsules must be able to flow by
gravity at about 350C or less.
 In general, liquids ranging in viscosity from 0.2 to 3000 cps. At 250C, can be encapsulated
without any difficulty, except in few cases like glycerin, where due to lack of tack, the blinding
of slide valves and pumps may be caused.
 The liquids to be filled in soft capsules generally call for no formulation and can be right away
filled.
 Liquids which cannot be capsulated thus are water (more than 5%), alcohols, ketones, acids,
amines, esters etc. which can leak through the capsule shell. Liquids with pH below 2.5 or above
7.5 should also be avoided since acidic liquids cause hydrolysis of the shell and alkaline ones
cause tanning affecting solubility characteristics of the shells.
 The same criteria holds good for solutions as well.
 The soft gelatin capsules these days are being increasingly used for encapsulation of suspensions
of solids in suitable bases.
 The important requirement that a suspension should necessarily meet is that it must have flow
properties similar to liquids and the suspended solids remain uniformly suspended during the
filling operation to ensure homogeneity of the encapsulated mix.
 To achieve this liquid bases should be carefully chosen. The common materials cited in literature
for this purpose are admixtures of vegetable oils and non-ionic surfactants, carbowax 400 etc.
 These bases could be used for oral as well as topical dosage forms. For veterinary dosage forms
aliphatic or aromatic hydrocarbons and chlorinated hydrocarbons can be chose alone or in
combination with the above mentioned materials.
Applications:
 Soft gelatin capsules are useful when it is desirable to seat medication within the capsule.
 Soft gelatin capsules are handsome and are easily swallowed by the patient.
 Examples of drugs dispensed in soft gelatin capsule are:-
o Vitamin E
o Digoxin
o Demectocycline HCL etc.
PHYSICAL STABILITY OF CAPSULES

 In the use of capsules one important aspect to be remembered is the physical stability of the
capsule shells under varying storage conditions.

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 In hard capsules excessive or low humidity conditions must be avoided as the former tend to
soften and the later can make the capsules brittle. The soft gelatin capsule rapidly attains
equilibrium with the environmental conditions.
 However, the nature of thee product encapsulated may have an effect on the capsule shell calling
for setting up of physical standards for each product.
 A control capsule, containing mineral oil with a gelatin shell having a ratio of dry glycerin: dry
gelatin between 0.5 to 1 and water to dry gelatin ratio of 1:1 dried to equilibrium at 20 to 30%
relative humidity at 70 to 800F is used as standard.
 This capsule unprotected by any other method will be only transiently effected by humidities
lower than 20% R.H. or temperatures ranging from less than 30F to more than 100F.
 As soon as extremes of conditions are removed the capsules return to normal form. High
humidities of more than 60% RH at 70 to 75F can have lasting effects making the capsules
bloated or softer and tackier. The capsules may also get stuck together and it may be difficult to
separate them.
 Increase in temperature beyond 750F along with high humidities (>45% RH) may fuse the
capsules. Capsules containing water soluble liquids are damaged t greater extents than the ones
having oleaginous products. It is better to expose newly developed capsules with or without
products packed in them to accelerated tests like exposure to 80% RH at room temperature and
to 1040F temperatures, in open as well as closed containers, and observe for 15 days. Such tests
give a fair idea of likely behaviour under storage conditions that capsules may have to face.
Manufacturers generally pack capsules in devices/containers designed to prevent exposure to
excessive humidity conditions and advise storage within certain temperature ranges only.
Advantages of Capsules:
 Capsules may be used for dispensing solid, semisolid and liquid drugs
 Avoidance of the contact with the unpleasant odour and flavor of medicines
 Easy to swallow
 Disintegration is both satisfactory and reliable
 Attractive dosage form
 Shells can be colored to give protection from light
 Shells are physiologically inert and are easily and quickly digested in GIT
 Less adjuncts are necessary than for tablets
 If properly stored, the shells contain 12-15% of moisture which gives flexibility and
consequently very considerable resistance to mechanical stresses
Disadvantages of Capsules:
 Capsules are expensive than tablets

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 They cannot be used for aqueous or alcoholic solutions as they will attack the shell
 Salts which are very readily soluble should not be capsulated as their sudden release will cause
the irritation
 Deliquescent or hygroscopic substances cannot be capsulated
 Insoluble substances such as some bismuth salts are reported to cause formation of enteroliths in
the intestine when administered in the form of capsules
GRANULES
Introduction:
The term Granules is derived from Latin word “Granulum” meaning little grain, Granules are
prepared from powdered substances, the particles which are made up of powders aggregate with the help
of solvent or binder.
Definitions:
 Granules are prepared Agglomerates of smaller particles.
 GRANULES are small particles gathered into a larger, permanent aggregate in which the
original particles can still be identified.
Shape and Size:

 They are generally irregular shaped and behave as single large particle.
 They are usually in 4-12 sieve size range, however granules of various mesh size maybe
prepared depending upon the requirements.

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Characteristics:
Bulk flow characteristics of granular materials do differ from those of homogeneous fluids in
several important ways:
 Shearing or shaking a granular material may result in its becoming inhomogeneous in space and
time
 Granular materials tend to clog when forced through a constriction
 A compacted granular material must expand (or dilate) before it can deform
 Turbulence is almost impossible to achieve in granular materials
 Granular materials can support (small) shear stresses indefinitely
 Granular materials are often inhomogeneous and anisotropic
 Granular materials exhibit avalanches
Types:
Granules can be categorized as follows.
1. Effervescent Granules:
Effervescent granules are uncoated granules generally containing acid substances and carbonates
or hydrogen carbonates which react rapidly in the presence of water to release carbon dioxide. They are
intended to be dissolved or dispersed in water before administration.
2. Coated Granules:
Coated granules are usually multi-dose preparations and consist of granules coated with one or
more layers of mixtures of various excipients.
3. Gastro-Resistant Granules:
Gastro-resistant granules are delayed-release granules that are intended to resist the gastric fluid
and to release the active substance(s) in the intestinal fluid. These properties are achieved by covering
the granules with a gastro-resistant.
4. Modified-Release Granules:
Modified-release granules are coated or uncoated granules which contain special excipients or
which are prepared by special procedures, or both, designed to modify the rate, the place or the time at
which the active substance or substances are released.
5. Granules Result after Wet Granulation:

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The following types of granules result after wet granulation.
A. Crust Granules:
A fluid substance is used to as a moistening agent that partially dissolves the contents. A
concentrated solution thus formed, leaves a crust after drying, which is then transformed into granules.
B. Binder Granules:
Gelatin, starch or similar substance is used as a binder in manufacturing this type of granules.
C. Sintered Granules:
When heat is employed to melt the substance during the manufacture process, such type of
granules is called sintered granules.
Granules Coating:
Granules may be coated in order to improve the flavor or to modify the release of drug.
Procedure:
A. IF SMALL DOSE OF DRUG IS REQUIRED
Starch granules of (25/20 mesh size) are first coated with an adhesive material, followed by the
powdered drug, and the pellets are dried. This process is repeated until the desired amount of drug
appears on the granules.
B. IF DOSE OF DRUG IS LARGE:
 The starting material may be drug itself, instead of the starch granules.
 The resultant granules are then subjected to coating with the required material.
 In case of slow release granules some of the granules may remain uncoated, to provide
immediate release,
 Others receive varying coats of lipid material like
o bees wax
o carnauba wax
o glyceryl-monostearate
o Cellulosic material like
o Ethylcellulose, or a mixture of both
Granules of different coating thickness are then obtained and the coating material maybe colored
in order to distinguish granules of different coating thickness.

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Desired Release Characteristics:
The granules of different groups are then blended properly in certain proportion, to attain the
desired release characteristics. In case of gastro-resistant or enteric coated formulations, there is a wide
range of choice of materials. These materials range from water-resistant films to pH-sensitive materials.
Some are digested or emulsified by intestinal juices, and some slowly swell and fall apart when solvated.
Many formulations use a combination of these effects to achieve the desired objective.
Examples of Materials used for Enteric Coating:
 Cellulose Acetate Phthalate (dissolves above pH 6.0) Acrylate Polymers (pH 6-7)
 Hydroxypropyl Methylcellulose Phthalate (pH 5.0-5.5) Polyvinyl Acetate Phthalate (pH 5.0-5.5)
 Sometimes sucrose or other flavoring agent is used to mask the undesirable taste of a
formulation.
Preparation:
Following Methods are employed for the preparation of granules:
1. Wet method which is further subdivided into;

a. Simple wet method
b. Fluid bed processing
2. Dry method which is further subdivided into;
a. Slugging method
b. Roll compactor method
WET METHOD:
A. SIMPLE WET METHOD:
In this method first step is the moistening of powder or powder mixture which is then passed
through a screen of the mesh size for the production of desired size of granules. The granules are placed
on drying trays and dried by air or under the heat and are periodically moved about on the drying trays
which prevents its adhesion into a large mass or bulk.
B. FLUID BED PROCESSING:
In this method particles are vigorously dispersed and suspended in a conical piece of equipment
while a liquid excipient is sprayed on them and the product on drying form granules or pellets of defined
particle size.

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DRY METHOD:
A. ROLL COMPACTOR METHOD:
The dry powder is passed through a roll compactor & then through a granulation machine. A roll
compactor, also called a Roll Press or Roller Compactor, processes a fine powder into dense sheets or
forms by forcing it through two mechanical rotating metal rolls running counter to each other. The
surface of the compacting rolls may be smooth or may have pocket indentations or corrugations
allowing compaction of different forms & textures. The compacted powder is granulated to uniform
particle size in a mechanical granulator. Powder compactors are generally combined in sequence in
integrated compactor granulation system.
B. SLUGGING METHOD:
In this method compression of powder or powder mixture into large tablet or slugs takes place by
a compressing machine under 8000 to 12000 pounds of pressure, depending on the physical
characteristics of the powder. The slugs are generally flat faced & about 2.5cm (1 inch) in diameter. The
slugs are granulated into the desired particle size, generally for use in the production of tablets. The dry
process often results in production of fines, which is powder that has not agglomerated into granules.
These fines are separated, collected & reprocessed.
TABLET GRANULES DOSAGE FORM GRANULES
It consists of grains which show It consists of grains that are as uniform as

considerable variation in size. possible.
It contains quite a large amount of It contains a minimum quantity powder.
powder.
Advantages of Granules:
 Easier to handle than powders
 Large doses are difficult to be formulated into tablets, so they can easily be given in the form of
granules
 The chemical and physical stability of granules is more than the mother powder
 Granules do not become hard mass or cake, on standing as powders do.
 The surface area of granules is much less than that of powders, so environmental factors have
less deteriorating effect on them.
 They get easily dissolved in water as compared to some light and fluffy powders which usually
float on the surface of water.
 They possess much better flow properties as compared to powders

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 They maybe coated with sugar or other material to mask the undesirable taste, but this cannot be
done with powders.
Disadvantages of Granules:
 Packaging of granules requires special care and is less economical than that of capsules and
tablets.
 It is difficult for the patient to measure the exact amount of dose to be taken.
 In case to damage to the packing material, the entire product gets exposed to environment,
whereas in case of tablets only single tablet gets exposed.
 The drugs liable to hydrolysis cannot be formulated in the form of granules, which mostly
require formation of aqueous solution or suspension prior to administration.
EFFERVESCENT GRANULES:
Definition:
Effervescent Granules or Salts are the coarse or very coarse powders containing a medicinal
agent in a dry mixture composed of sodium bicarbonate, citric acid and tartaric acid.
Explanation:
When added to water they liberate carbon dioxide due to the reaction of acids and bases. This is
the basic cause of production of effervescence. The carbonated solution produced due to above reaction
masks the saline or undesirable taste of medicinal agent present. Citric acid and tartaric acid are used
together for ease. If tartaric acid is used alone as acid then granules produced will lose their firmness and
crumbliness will be the result. Similarly if citric acid is used alone then results will be a sticky mixture
difficult to granulate.
Methods of Preparation:
Effervescent Granules are produced by two general methods:-
FUSION METHOD:
In this method, one water molecule in each molecule of citric acid will act as binding agent for
the powder mixture. The citric acid crystals are powdered before mixing with other powders. Then it is
mixed with the other powders of same sieve size to ensure the uniformity of mixture. To avoid the effect
of acids the sieve and other equipments should be made of stainless steel or other resistant material. The
mixing of powders is done rapidly. Similarly to avoid the absorption of moisture and premature
chemical reaction, the mixing is done in an environment of low humidity. The powder is placed on a
suitable dish in an oven at 34°C to 40°C. In heating process, an acid-resistant spatula is used to turn the
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powder. The water of crystallization will be released during the heating. So in the result of this some
portion of the powder will be dissolved and the reaction will set which in turn releases carbon dioxide.
Due to release of carbon dioxide and the reaction the soft mass of powder will turn into spongy when it
become as bread dough. It is removed from the oven and rubbed through sieve of desired size. A No. 4
sieve produces granules of size large. Similarly a No. 8 produces medium size and No. 10 of small size
granules. The granules are dried at a temperature of 54°C not more than that. It is immediately placed in
containers and tightly sealed.
WET METHOD:
It is another method of preparation of Effervescent Granules. The main difference between wet
method and fusion method is that in wet method the binding agent is the water added in the alcohol as
the moistening agent, forming a pliable mass for granulation. The liquid is added in portions till a mass
like bread dough is formed. Then granules are prepared by usual method of granulation through sieve.
Significance:
Effervescent Granules have following significances:
1. They have effective effervescence.

2. In this effective utilization of the acids and bases present.
3. There is a stable granulation.
4. They have pleasant tasting.
5. They are efficacious product.

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POWDERS
Definition:
 Powders are intimate mixture of dry finally divided drugs or chemicals that may be
intended for internal or external purposes.
 Powders are solid dosage form of medicaments which are meant for internal and external
uses.
Introduction:
 They are available in amorphous or crystalline form.
 Drugs are prepared in different forms and shapes but many of them are prepared by using
powder in one way or the other.
 Powder used as dosage forms may be prepared from:

o A naturally occurring vegetable drug.
o A physical admixing of two or more powdered pure chemical agents present in
definite proportions.
o Powders may contain small proportions of liquids dispersed thoroughly and
uniformly over the solid components of the mixture or may be composed entirely
of solid materials.
Powders and Particle Size:
 The physiochemical properties of powders are largely dependent upon the size and
surface area of particles.
 The particles of pharmaceutical powders may be very fine (1u or less), maybe very
coarse (10,000u or 10 mm).
 In order to standardize particle size of a powder, USP employs descriptive terms

depending upon proportion of powder that is capable of passing through the opening of
standardize sieves of varying dimensions in a specified time period under shaking in
mechanical shaker.
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USP defined powders as:
 VERY COARSE: (no.8): All particles pass through this sieve and no more than 20%
through no. 60 sieve.
 COARSE: (no.20): All particles pass through this sieve and no more than 40% through
no.60 sieve.
 MODERATELY COARSE: (NO.40): All particles pass through this sieve and no more
than 40% through a no.80 sieve.
 FINE: (no.60): All particles pass through this sieve and no more than 40% through no.
100 sieve.
 VERY FINE: (no.80): All particles pass through this sieve and no limit as to greater
fineness.
Particle size can influence:
 DISSOLUTION RATE: Drug micronization can increase the rate of drug dissolution
and its bioavailability.
 SUSPENDABILITY: Suspendability of particles intended to remain same, but
uniformly dispersed in a liquid vehicle.
 DISTRIBUTION: Uniform distribution of a drug substance in a powder mixture form to

ensure dose-to- dose uniformity.
 NONGRITTINESS: Lack of grittiness of solid particles in dermal ointments, creams,

ophthalmic preparations.
Determination of Particle Size:
 SIEVING: Particles are passed by series of sieves of known and successively smaller
size by shaking.
 LIGHT ENERGY DIFFRACTION: In which particle size is determined by reduction
in light reaching the sensor as the particle, dispersed in a liquid or gas, passes through
the sensing zone.
 MICROSCOPY: In which particle size are sized through the use of a grid.
 SEDIMENTATION RATE: In which particle size is determined by measuring terminal
settling velocity of particles through a liquid medium.

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 CASCADE IMPACTION: Particles are separated into various size ranges by
successively increasing velocity of airstream in which they are carried.
 LASER HOLOGRAPHY: A pulsed laser is fired through n aerosolized particle spray
and is photographed in 3 dimensions with a holographic camera, allowing particles to be
imaged and sized individually.
ADVANTAGES OF POWDER:
 Powders are more stable than liquid dosage forms because of reactions between drug and
drug, drug and other substance.
 Rate of dissolution is more than that of capsule , tablets etc
 Rapid dissolution produces high blood levels in shorter time.

 Easy to swallow even in bulk form, when mixed with food or drink.
 Used as a dry lubricant
 As a drying agent
 As adsorbent of bacteria, bacterial toxins, poisons , gases etc
 It is cheap and wastage is minimum
DISADVANTAGES OF POWDERS:
 Drugs which deteriorate upon exposure to atmospheric conditions cannot be dispensed

properly in powder dosage forms.
 Bitter, nauseating or corrosive drugs cannot be dispensed in powder form.
 Powders are costly than tabelets and capsules, as there preparation is more time
consuming.
 Inaccuracy of dose in bulk powders is another disadvantage.
 Packaging may prove costly.
CLASSIFICATION OF POWDERS:
ACCORDING TO THE NO. OF ACTIVE INGREDIENTS PRESENT:
1. Simple powders
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2. Compound powders
SIMPLE POWDERS:
 This dosage form consists of one active ingredient mixed with some inert substance i.e.
lactose, starch.
EXAMPLE:
 Hyoscine hydrobromide powder used as an anti-emetic.

COMPOUND POWDERS:
 This dosage form contains more than one active ingredient.

EXAMPLE:
 Compound bismuth powder

 Compound effervescent powder.
 Compound kaolin powder.
ACCORDING TO MODE OF DISPENSING:
1. Bulk powders.
2. Divided powders.
BULK POWDERS:
 These are the types of powders which are not divided into doses before being handed to
the patient.
 Generally less potent drugs are supplied in the form of bulk powders.
 These are packed in bulk containers after preparation with special directions on the label
for mixing, usage and dosage.
 Boric acid and ZnO Powder used as dusting powder for face and neck.
EXAMPLE:
 Rhubarb powder.
DIVIDED POWDERS:
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 After preparation of powder, it may be divided into individuals units based upon the dose
to be administered at a single time.
 Potent drugs and those drugs that should be administered in controlled dosage are usually
supplied to the patient in divided powders.
 Each divided portion of powder is placed on a small piece of paper which is then folded
so as to enclose the medication.
EXAMPLE:
 Headache powders
 Laxatives powders
 ORS
PREPARATION OF POWDERS:
Following are the steps for preparation of powders:
1. SPATULATIONS: Small amounts of powders, having same range of particle size and
densities maybe mixed on a sheet of paper with spatula.
2. TRITURATION: Powders may be mixed in a mortar to attain properties of lightness and

diffusibility.
3. SIFTING: Compound powders containing vegetable substances often requires sifting to

break up the small masses of cohering particles. When free flowing, light powders are desired,
ingredients maybe brushed through a sieve.
4. TUMBLING: When simple mixing powders is desired without reduction in particular size.
Wide mouthed containers are used, they rotate generally by a motorized process. Tumbling is
recommended for mixing powders with considerable density difference.
PACKAGING OF POWDERS:
Packaging takes place in two ways:
DIVIDED POWDER PACKAGING OR UNIT DOSE PACKAGING:
 It is used for potent drugs or for drugs to be used at controlled rate and dosage.

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 Powder after mixing is divided into portion and then wrapped in a paper to enclose the
required amount for single dose.
 These single dose wrappers are then packaged in envelopes or boxes.
 If powder, for divided packaging is, hygroscopic, volatile etc then an inner wrapper of
parchment is necessary.
BULK PACKAGING OR MULTIDOSE PACKING:
 This is recommended for less potent drugs.

 Bulk powders are usually sent out in screw capped jars or bottles with mouth sufficiently
wide to take tea spoon as required.
 They may be supplied in the form of aerosols.

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TABLET DOSAGE FORM

Introduction:
 Tablets are the most common solid dosage form that is given by Oral route (GIT).
 They are safer than injectables.
 Pills are small, round, solid dosage forms containing a medicinal agent and intended for oral
administration. Nowadays pills have been replaced by tablets and capsules.
 Friable pills were first prepared by Upjohn in the 1950s. Later, pills were replaced by
compressed tablets.
Definition:
 Tablets may be defined as solid dosage pharmaceutical forms containing drug substances
with or without suitable diluents and prepared either by compression or molding method.
 Tablets are solid dosage forms usually prepared with the aid of suitable pharmaceutical
excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and
dissolution characteristics and in other aspects depending on their intended use and method
of manufacturing.
 Tablets may be defined as the solid unit dosage form of medicament or medicaments with or
without suitable diluents and prepared either by molding or by compression
 A tablet is a mixture of active substances and excipient, usually in powder form, pressed or
compressed or compacted into a solid. The excipient include binders, glindants (flow aids)
and lubricants to ensure efficient tableting, disintegrates to ensure that the tablets break up in
the digestive tract; sweetness or flavor to mask the taste of bad-tasting active ingredients and
pigments to make uncoated tablets, visually attractive.
Properties of Tablets:
The properties of tablets are following:
 They are different in shape, size and weight which depend upon the amount of medicament
and the mode of administration.
 It should be an elegant product having its own identity.
 It should have the strength to withstand the rigors of mechanical shocks.
 It should have the chemical and physical stability to maintain its physical attributes.
 It must be able to release the mechanical agent.
 Tablets are disk shaped with convex surfaces but they are also-available in special shapes
like round, oval, oblong, cylindrical, square, triangular etc.

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 The weight of oral tablets may range from 0.2 to 0.8 gm including the diluents but the tablets
meant for administration other than oral route may be lighter or heavier.
 They offer a number of advantages to the patient, prescribers‟ manufacturer and the
manufacturing pharmacist.
 Because of these advantages their popularity is continuously increasing day by day.
Composition of Tablets:
 It comprises a mixture of active substances and excipients, usually in powder form,
pressed or compacted from a powder into a solid dose.
 The excipients can include diluents, binders or granulating agents, glidants (flow aids) and
lubricants to ensure efficient tableting; disintegrants to promote tablet break-up in the
digestive tract; sweeteners or flavors to enhance taste; and pigments to make the tablets
visually attractive.
 A polymer coating is often applied to make the tablet smoother and easier to swallow, to
control the release rate of the active ingredient, to make it more resistant to the environment
(extending its shelf life), or to enhance the tablet's appearance.
Properties of Excipients:
 It should be Inert – shouldn‟t have pharmacological effect.
 It should be compatible with API – shouldn‟t later the API.
 It should be cheap.
 It should be easy to handle.
 It should be stable and pure.
Selection Criteria of Excipients:

 It should give proper shape to tablet.
 It should have proper weight.
 It should have proper hardness.
 It should have proper rate of dissolution.
 It should have proper disintegration.
 It should have friability – strength of tablet to withstand with the shock and aberration.
Characteristics of an Ideal Tablet:

1. FREE OF DEFECTS:
A tablet should be an elegant product having its own identity while being free of defects
such as contamination, chips, cracks and discoloration.
2. PHYSICAL STABILITY:
A tablet should have the chemical and physical stability to maintain its physical attributes
over time .Various physical properties of tablets can undergo change under the environment or
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stress conditions and that physical stability, through its effects on bioavailability in particular can be
of more significance.
3. CHEMICAL STABILITY:
A tablet should have the chemical and physical stability to maintain its physical attributes
over time so as not to allow alternation of medicinal agents.
4. RELEASE OF MEDICINAL AGENTS:

The tablet must be able to release the medicinal agents in the body in a predictable manner
and reproducible manner.
5. STRENGTH:
A tablet should have strength to withstand the rigors of mechanical shocks encountered in its
production, packaging, shipping and dispensing.
6. COLOUR:
The colour of product must be uniform within a single tablet. Non uniformity of coloring not
only lacks esthetic appeal but could be associated by the consumer with non- uniformity of content
and general poor quality of product.
7. ODOUR:
The presences of an odour in a batch of tablets could indicate a stability problem, such as the
characteristics odour of acetic acid in degrading the aspirin tablets.
Note:
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 coating and / or drug-release
features that would be compromised by altering the tablet‟s physical integrity.
Types and Classes of Tablets:

There are four major types of tablets. These are following:
1. Tablets ingested orally

2. Tablets used in oral cavity
3. Tablets administered by other routes
4. Tablets used to prepare solutions
1. Tablets Ingested Orally:

Orally ingested tablets are designed to be swallowed intact, with exception of chewable
tablets. These are further classified as:
A. Compressed tablets

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B. Multiple compressed tablets.
A. Compressed Tablets:
These tablets are swallowed as such. They are placed over the tongue and swallowed with a
drink of water or any other suitable liquid. Most of them are formulated in such a way that they
disintegrate in the stomach and dissolve in the gastric fluids thus absorption takes place from there.
Compressed tablets are prepared by single compression using tablet machines. After a
quantity of powdered or granulated tableting material flow into a die, the upper and lower punches
of the tablet machine compress the material under a high pressure (~tons/in2). This category refers
to standard uncoated tablets made by compression and employing any of three basic methods of
manufacture.
They include two types of tablets.
I. Direct Compressed Tablets

II. Wet Granulation Tablets
B. Multiple Compressed Tablets:

Multiple compressed tablets are prepared by subjecting the fill material to more than a single
compression. This results into two types of tablets:
 Layered Tablets
These are the compressed tablets in which the granules of incompatible substances are
compressed into two or more layers successively in the same tablet. Special tablet making
machines are required for making layered tablets. Layered tablets are prepared by initial
compactation 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.
 Compression Coated Tablets (Tablet within tablet)
In preparation of compression coated tablets special machines are required to place the
performed core tablet precisely within the die for application of surrounding fill material.
Examples include Norgesic Tablet.
This class is further divided into following subclasses. These are as follow:
i. Repeat-action tablets
ii. Delayed-action and enteric coated tablets
iii. Sugar and chocolate coated tablets
iv. Film coated tablets
v. Chewable tablets
ADVANTAGE:

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An advantage of multiple compressed tablets is that medicinal agents are separated to
prevent incompatibility, or each layer provides drug release at a different stage or for coating
purposes.
DISADVANTAGE:
It is tedious and expensive process and requires accurate and precise machinery.
i. Repeat Action tablets:
The mode of operation of repeat action coated tablets and their limitations are based on
uncontrolled and unpredictable gastric employing.
ii. Delayed Action and Enteric Coated Tablets:
The delayed action and enteric coated dosage form is intended to release a drug after
sometime delay, or after the tablet has passed through one part of GI tract into another. Ecotrine
tablets and caplets are example.
ADVANTAGES:
 Protects drugs that are destroyed in acid medium.

 Protects the stomach from drugs that cause irritation to the gastric mucosa.
iii. Sugar and Chocolate Coated Tablets:
Compressed tablets may be coated with colored or uncolored sugar layer. This coating is
water soluble and quickly dissolves after swallowing.
ADVANTAGES:
 Sugar coat protects drug from effects of air and humidity.

 It provides a barrier to objectionable taste or odor.
 Enhances the appearance of compressed tablets and permits of identifying manufacturer‟s
information.
DISADVANTAGES:
 Time and Expertise is required in the coating process.

 Size and weight is increased (50 %) so shipping cost is also increased.
iv. Film-coated Tablets:
Film-coated tablets are compressed tablets coated with a thin layer of a polymer capable of
forming a skin line film. By its composition, the coating is designed to rupture and expose the core
tablet.
ADVANTAGE:
These have an advantage over sugar coated tablets that they are more durable, less bulky,
and less time consuming to apply.

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v. Chewable Tablets:
 Chewable tablets are intended to be chewed in the mouth prior to swallowing and are not
intended to be swallowed intact. It can easily administer to children. A number of antacid
tablets and multivitamin tablets are prepared as chewable tablets.
 For the preparation of chewable tablets mannitol is used as a base.
 It is a white crystalline, chemically inert, non hygroscopic, thermo stable powder and is as
sweet as that of glucose.
 It does not have any objectionable effects but since it is expensive so i cannot be used in
tablets of low cost, therefore other substances like sorbitol lactose, chocolate powder,
dextrose and glycine can be substituted in place of mannitol
 These tablets should have very acceptable taste and flavor. They should disintegrate in a
short time and produce cool sweet taste. Chewable tablets can be taken at any place even if
water is not available. These tablets do not require any disintegrating agent to be present in
the formulation. The use of gums and other substances which produce hard granules should
be avoided. The lubricants used should have agreeable taste.
ADVANTAGE:
Chewable tablets are mainly used mainly for children‟s multivitamin tablets and for the
administration of antacids and anti-flatulent. Examples are Pepcid chewable tablets and Rolaids
chewable tablets.
2. Tablets Used in Oral Cavity:

Tablets that are used in oral cavity are further classified in to two types. These are following:
i. Buccal Tablets
ii. Sublingual Tablets
iii. Troches and Lozenges
iv. Dental Cones
i. Buccal and Sublingual Tablets:
These two classes of tablets are intended to be held in the mouth. These are flat oval shaped
tablets. It is used because some of the drugs destroyed in gastric mucosa. These tablets contain large
proportions of sweetening agents like mannitol and/or sucrose to impart sweetness.
ADVANTAGE:
Sublingual tablets are used for drugs that are destroyed by gastric juice and/or are poorly
absorbed from the GI tract.
ii. Troches and Lozenges:
 These are two other types of tablets used in the oral cavity, where they are intended to exert
a local effect in the mouth or throat. These are made by moulding process.
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 Lozenges tablets should not disintegrate in the oral cavity but should dissolve slowly in the
mouth to produce continuous effect on the mucous membrane of the throat.
 They can be prepared by molding as well as by compression method.
 The lozenges prepared by compression are known as lozenge tablets.
 the formulation of lozenges contain no disintegrating agent
 The quantity of binding agent is increased so as to induce slow dissolution.
 The formulation must contain sweetening and flavoring agents.
iii. Dental Cones:
These are relatively minor tablet forms that are designed to be placed in the empty socket
remaining following a tooth extraction. Their usual purpose is to prevent the multiplication of
bacteria.
3. Tablets Administered by Other Routes:

There are two subclasses of tablets administered by other routes. These are as follow:
 Implantation Tablets
 Vaginal Tablets
i. Implantation Tablets:
 Implantation or depot tablets are designed for subcutaneous implantation in animals or man.
Their purpose is to provide prolonged drug action. These tablets are usually small,
cylindrical or rosette-shaped forms and are typically not more than 8mm in length.
 Since these tablets are to be implanted intramuscularly or subcutaneously therefore they
must be sterile.
 They must be prepared under aseptic conditions and packed in unit dose sterile containers.
 No excipients are used and they are compressed under heavy pressure.
 These tablets are more commonly used in veterinary medicine than human medicine.
 They can also be used for birth control in human beings. Generally steroidal hormones like
testosterone, stilbesterol etc. are formulated as implants.
ii. Vaginal Tablets:
Vaginal tablets or inserts are designed to undergo slow dissolution and drug release in the
vaginal cavity. The tablets are typically ovoid or pear-shaped to facilitate retention in the vagina.
This tablet form is used to release antibacterial agents, antiseptics or astringents to vaginal infection.
Some laxative suppositories are also formulated as compressed tablets. The active medicaments are
mixed with such disintegrating agents who either swell up after absorbing moisture or produce
effervescence thus facilitating disintegration. These rectal tablets are covered with thin layers of
polyethylene glycol which act as protective covering and also facilitate the insertion of these
tablets into the rectum.

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4. Tablets Used to Prepare Solutions:
Tablets used to prepare solutions are divided into subclasses. These are as follow:
i. Effervescent Tablets
ii. Dispensing Tablets (DP)
iii. Tablets Triturates (TT)
iv. Hypodermic Tablets (HT)
i. Effervescent Tablets:
 These tablets are designed to provide a solution rapidly with the simultaneous release of
carbon dioxide.
 The tablets are typically prepared by compressing the active ingredients with mixtures of
organic acids such as citric acid or tartaric acid.
 The most widely produced effervescent tablet is one that contains Aspirin.
 Examples are Alka-Seltzer Original and Zantac EFFER dose.
ADVANTAGE:
 Fast disintegration and dissolution of drug for rapid action (alkalinizing analgesic tablets).
ii. Dispensing Tablets:
 Dispensing tablets are intended to be added to a given volume a water by the pharmacist or
the consumer, to produce a solution of a given drug concentration.
 Materials that have been commonly incorporated in dispensing tablets include mild silver
proteinate, bichloride of mercury, merbronium and quaternary ammonium compounds.
 Dispensing tablets are less commonly used or they‟re no longer in use.
 These tablets had the dangerous potential of being inadvertently dispensed as such to
patients.
iii. Tablets Triturates:
 Tablets triturates are small, usually cylindrical, molded or compressed tablets.

 These are rarely used tablets. Generally potent medicaments and highly toxic drugs in small
doses are used for preparing the molded tablets.
 They provided an extemporaneous method of preparation.
 The potent medicament is diluted with a diluents like Lactose, Dextrose,
 The mixed powders are moistened with a suitable dilution of alcohol.
 The soft mass so prepared is pressed into perforations of the mold with a spatula
 The excess of the mass is removed by applying pressure over the spatula.
 This perforated plate of the mold filled with the mass is placed over another plate having
exactly the same number of projecting pegs as that of to get a soft mass.
 The perforations and these projecting pegs completely fit into the holes.

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 A little pressure is applied over top plate which will force the plate move downward, leaving
the molded tablets on the projecting pegs.
 The ejected tablets are spread in single layers on clean surface and dried either by keeping in
a warm place or hot air oven.
 Now a day‟s tablet triturates may also be prepared on automatic tablet triturate machines.
 A tablet triturate machine can prepare 2500 tablet triturates per minute.
 Pharmacists also employ tablet triturates in compounding.
 For example, triturates are inserted in capsules or dissolved in liquid to provide accurate
amounts of potent drug substances.
iv. Hypodermal Tablets:
 They were originally used by physicians in extemporaneous preparation of parental

solutions.
 These tablets are composed of one or more drugs with other readily water soluble
ingredients are intended to be added to sterile water or water for injection.
 These are less used tablets today.
 Hypodermic tablets are soft readily soluble tablets which are made in a tablet triturate mold.
 They are used for preparing solutions to be injected, therefore in selecting the materials used
for preparing the hypodermic tablets care must be taken that they should be completely and
readily soluble and no insoluble particle should be present.
 They should be free from bacterial contamination and proper precautions should be taken
during molding regarding contamination and cleanliness.
 Since the solutions prepared from hypodermic tablets are rarely sterile and a number of
sterile parenteral solutions are now available therefore the use of hypodermic tablets for
preparing solution for injections is being discouraged. They are no longer used.
Methods to Prepare Tablets:

There are four methods to prepare tablets. These are as follow:
1. Direct Compression Method

2. Wet Granulation Method
3. Dry Granulation Method
4. Fluid Bed Granulation Method
1. Direct Compression Method:

 Some granular chemicals, like potassium chloride, possess free-fl owing 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:

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o Spray-dried lactose
o Micro-crystals of alpha-monohydrate lactose
o Sucrose–invert sugar–corn starch mixtures,
o Microcrystalline cellulose
o Crystalline maltose
o Dicalcium phosphate
o Disintegrating agents, such as direct compression starch, sodium carboxymethyl starch,
cross-linked carboxymethylcellulose fibers, and cross-linked polyvinylpyrrolidone;
lubricants, such as magnesium stearate and talc
o Glidants, such as fumed silicon dioxide.
 Binders include such as:
o Carboxymethylcellulose, sodium cellulose, microcrystalline, starch
o Agar, acacia gum, glucose
 The capping, splitting, or laminating of tablets is sometimes related to air entrapment during
direct compression.
 When air is trapped, the resulting tablets expand when the pressure of tableting is released,
resulting in splits or layers in the tablets.
 Forced or induced feeders can reduce air entrapment, making the fill powder more dense and
amenable to compaction.
 Lubricants are used to:
o Improve the flow of granules in the hopper to the die cavity
o Prevent sticking of tablet formulation to the punches and dies during formulation
o Reduce the friction between the tablet and the die wall during the tablet‟s ejection from
the tablet machine.
o Give sheen to the finished tablets.
2. Wet Granulation Method:

Wet granulation is a widely employed method for the production of compressed tablets. The
steps required are
a) Weighing and blending the ingredients

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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
A. Weighing and blending the ingredients:
Specified quantities of active ingredient, diluent or filler, and disintegrating agent are mixed
by mechanical powder blender or mixer until uniform. Fillers include lactose, microcrystalline
cellulose, starch, powdered sucrose, and calcium phosphate. The choice of filler usually is based on
the experience of the manufacturer with the material, its relative cost, and its compatibility with the
other formulation ingredients.
Disintegrating agents include croscarmellose, corn and potato starches, sodium starch
glycolate, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), crospovidone, cation
exchange resins, alginic acid, and other materials that swell or expand. The total amount of
disintegrant used is not always added in preparing the granulation. Often a portion (sometimes half)
is reserved and added to the finished granulation prior to tablet formation. This results in double
disintegration of the tablet. One portion assists in the breakup of the tablet into pieces and the other
portion assists in the breakup of the pieces into fine particles. On exposure to moisture and effect the
rupture or breakup of the tablet in the gastrointestinal tract occur.
B. Preparing a dampened powder or a damp mass:

A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles.
Either a dampened powder formed into granules or a damp mass resembling dough is formed and
used to prepare the granulation. A good binder results in appropriate tablet hardness and does not
hinder the release of the drug from the tablet. The binding agent contributes to adhesion of the
granules to one another and maintains the integrity of the tablet after compression. However, care
must be exercised not to overwet or underwet the powder. When desired, a colorant or flavorant
may be added to the binding agent to prepare a granulation with an added feature.
C. Screening the dampened powder or 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.
D. Drying the Granulation:
Granules may be dried in thermostatically controlled ovens that constantly record the time,
temperature, and humidity.

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E. 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. Screens of 12- to 20-mesh size are generally used for this purpose. Voids
or air spaces left by too large a granulation result in the production of uneven tablets.
F. Adding lubricant 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:
 They improve the flow of the granulation in the hopper to the die cavity.
 They prevent adhesion of the tablet formulation to the punches and dies during compression.
 They reduce friction between the tablet and the die wall during the ejection of the tablet from
the machine.
 Among the more commonly used lubricants are magnesium stearate, calcium stearate, stearic
acid, talc, and sodium stearyl fumarate. Magnesium stearate is most used.
3. Dry Granulation Method:

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.
Two process involve in dry granulation method that are
A. Slugging
B. Roller Compactation

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A. 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.
B. Roller Compactation:
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 or hydroxyl methylcellulose (6% to 12%), which can produce good tablet
hardness and friability.
ADVANTAGES
 May produce up to 1150 tablets per minute

 Double rotary presses produce 2 tablets for each die.
DISADVANTAGES
 Lamination (horizontal striations) occur due to high

speed.
 Capping, in which top of the tablet separates from the
whole because fill material does not have enough time to bond after compression.
4. Fluid Bed Granulation Method:

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. This is the
latest method of preparation of tablet.

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Process after Preparation:
After preparation of tablets, tablets undergoes following processes:
1. 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.
2. Tablet Coating:
Tablets are coated for a number of reasons, including to protect the medicinal agent against
destructive exposure to air and/or humidity; to mask the taste of the drug; to provide special
characteristics of drug release (e.g., enteric coatings); and to provide aesthetics or distinction to the
product.
3. Waterproofing and Sealing Coats:
For tablets containing components that may be adversely affected by moisture, one or more
coats of a waterproofing substance, such as pharmaceutical shellac or a polymer, are applied to the
compressed tablets before the sub-coating application. The waterproofing solution (usually
alcoholic) is gently poured or sprayed on the compressed tablets rotating in the coating pans. Warm
air is blown into the pan during the coating to hasten the drying and to prevent tablets from sticking
together.
4. Sub-coating:
After the tablets are waterproofed if needed, three to five subcoats of sugar-based syrup are
applied. This bonds the sugar coating to the tablet and provides rounding. The sucrose and water
syrup also contains gelatin, acacia, or PVP to enhance coating. When the tablets are partially dry,

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they are sprinkled with a dusting powder, usually a mixture of powdered sugar and starch but
sometimes talc, acacia, or precipitated chalk as well.
5. Smoothing and Final Rounding:
After the tablets are subcoated, 5 to 10 additional coatings of thick syrup are applied to complete
the rounding and smooth the coatings. This syrup is sucrose based, with or without additional
components such as starch and calcium carbonate. As the syrup is applied, the operator moves his or
her hand through the rolling tablets to distribute the syrup and to prevent the tablets from sticking to
one another. A dusting powder is often used between syrup applications. Warm air is applied to
hasten the drying time of each coat.
6. Finishing and Colouring:
To attain final smoothness and the appropriate color to the tablets, several coats of thin syrup
containing the desired colorant are applied in the usual manner. This step is performed in a clean
pan, free from previous coating materials.
7. Imprinting:
Solid dosage forms may be passed through a special imprinting machine to impart
identification codes and other distinctive symbols. Technically, the imprint may be debossed,
embossed, engraved, or printed on the surface with ink. Debossed means imprinted with a mark
below the surface; embossed means imprinted with a mark rose above the surface; and engraved
means imprinted with a code that is cut into the surface during production.
8. Polishing:
Coated tablets may be polished in several ways. Special drum-shaped pans or ordinary coating
pans lined with canvas or other cloth impregnated with carnauba wax and/or beeswax may be used
to polish tablets as they tumble in the pan. Or, pieces of wax may be placed in a polishing pan and
the tablets allowed tumbling over the wax until the desired sheen is attained. A third method is light
spraying of the tablets with wax dissolved in a non-aqueous solvent.
9. Packing process:
At the end of all above, packing of tablets has done with packing machine and tablets are
available in market.
Problems Associated in the Manufacturing of Tablets:

There are two major problems associated in the manufacturing of tablets. These are as
follow:
1. In-process Manufacturing Issues

2. Post Manufacturing Issues

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Basic
Problems
Mechanical Release
Weight Content Visual
Strength Profile
Variation Uniformity defects
Related Altered
Hardness Friability
1. in-process Manufacturing Issues:

These problems occurred during manufacturing of tablets. There are following problems
occurred during manufacturing of tablets:
i. Capping and Lamination:
 Capping is a term used to describe the partial and the complete separation of the top or
bottom crowns of tablet from main body of tablet.
 Lamination is the separation of the tablet into two or more distinct layers. Capping and
lamination encountered in direct compression.
ii. Picking and Sticking:
 Picking is a term used to describe the surface material from a tablet sticking to and being
removed from tablet‟s surface.
 In some cases, colloidal silica is added to formula acts as polishing agent and makes the
punch faces smooth.
iii. Mottling:
 Mottling is an unequal
Capping
distribution of color on the
tablet, with light or dark areas Lamination
Process
standing out in otherwise Related
Cracking
uniform surface.
 One cause of mottling is a Chipping
drug whose color differs from
tablet excipients or a drug Visual Sticking
Defects
whose degradation products Formulation
Picking
are colored. Related
Binding
iv. Punch Variation:
Machine Double
Related Impression

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Thousandths of an inch the fill in each die varies because the fill is volumetric.
v. Hardness Variation:
Hardness variation may occur due to personal or mechanical error.
vi. Double Impression:
This problem involves only punches that have monogram or other engraving on them. At the
moment of compression, the tablet receives imprint of the tablet.
2. Post Manufacturing Issues:

 These are the problems occurred after manufacturing of tablets. One of the basic problem
occurred during transportation of the tablets. In process of transportation, tablets broken
down that is called Friability.
 This cause the loss of therapeutic efficacy of the tablets. Others are disintegration and
dissolution problems.
Quality Control Tests of Tablets:

There are two major types of quality control tests of tablets and these are as follow:
 Official Tests
 Non-official Tests
Official Tests:
These tests include
 Disintegration Tests
 Dissolution Tests
 Friability Tests
Disintegration Tests:
Tablet disintegration also is important for tablets containing medicinal agents (such as
antacids and anti-diarrheals) 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. During testing, a tablet is placed in each of the six tubes of the basket, and through the
use of a mechanical device, the basket is raised and lowered in the immersion fluid at 29 to 32
cycles per minute, the wire screen always below the level of the fluid. For uncoated tablets, buccal
tablets, and sublingual tablets, water at about 37°C serves as the immersion fluid unless another
fluid is specified in the individual monograph. For these tests, complete disintegration is defined as

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“that state in which any residue of the unit, except fragments of insoluble coating or capsule shell,
remaining on the screen of the test apparatus is a soft mass having no palpably firm core”. Tablets
must disintegrate within the times set forth 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.
Dissolution Test:
In vitro dissolution testing of solid dosage forms is important for a number of reasons:
1. It guides formulation and product development toward product optimization. Dissolution

studies in the early stages of a product‟s development allow differentiation between
formulations and correlations identified with in vivo bioavailability data.
2. Manufacturing may be monitored by dissolution testing as a component of the overall
quality assurance program. The conduct of such testing from early product development
through approval and commercial production ensures control of any variables of materials
and processes that could affect dissolution and quality standards.
The USP includes seven apparatus designs for drug release and dissolution testing of
immediate-release oral dosage forms, extended release products, enteric-coated products, and
transdermal drug delivery devices. The equipment consists of:
(a) A variable speed stirrer motor

(b) A cylindrical stainless steel basket on a stirrer shaft (USP Apparatus 1) or a paddle as the
stirring element (USP Apparatus 2)
(c) A 1,000-mL vessel of glass or other inert transparent material fitted with a cover having a
center port for the shaft of the stirrer and three additional ports, two for removal of samples
and one for a thermometer
(d) A water bath to maintain the temperature of the dissolution medium in the vessel. For use of
USP Apparatus 1, the dosage unit is placed inside the basket. For use of USP Apparatus 2,
the dosage unit is placed in the vessel. In each test, a volume of the dissolution medium (as
stated in the individual monograph) is placed in the vessel and allowed to come to 37°C ±
0.5°C. Then the stirrer is rotated at the speed specified, and at stated intervals, samples of the
medium are withdrawn for chemical analysis of the proportion of drug dissolved. The tablet
or capsule must meet the stated monograph requirement for rate of dissolution.
Friability:
A tablet‟s durability may be determined through the use of a friabilator. This apparatus
determines the tablet‟s friability, or tendency to crumble, by allowing it to roll and fall within the
drum. The tablets are weighed before and after a specified number of rotations and any weight loss
is determined. Resistance to loss of weight indicates the tablet‟s ability to withstand abrasion in
handling, packaging, and shipment. A maximum weight loss of not more than 1% generally is
considered acceptable for most products.

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2. Non Official Tests:
These tests include
 Weight Variation
 Thickness of Tablets
 Hardness of Tablets
 Diameter of Tablets
Weight Variation:
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 homogenous drug distribution.
Thickness of Tablets:
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. Thus, for tablets of uniform
thickness and hardness, it is doubly important to control pressure. Tablet thickness may be measured
by hand gauge during production or by automated equipment.
Hardness of Tablet:
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 4 kg
is considered the minimum requirement for a satisfactory tablet. Multifunctional automated
equipment can determine weight, hardness, thickness, and diameter of the tablet.
Sr. CAUSES REMIDIES

The Causes and Remedies of Capping related to ‘Formulation’
1. Large amount of fines in the granulation Remove some or all fines through 100 to 200
mesh screen
2. Too dry or very low moisture content Moisten the granules suitably. Add
(leading to loss of proper binding action). hygroscopic substance e.g.: Sorbitol,
Methylcellulose or PEG-4000.
3. Not thoroughly dried granules. Dry the granules properly.
4. Insufficient amount of binder or Increasing the amount of binder OR
improper binder. Adding dry binder such as pre-gelatinized
Starch, Gum acacia, powdered Sorbitol, PVP,
hydrophilic Silica or powdered Sugar.
5. Insufficient or improper lubricant. Increase the amount of lubricant or change the
type of lubricant.
6. Granular mass too cold to compress firm. Compress at room temperature.

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The Causes and Remedies of Capping related to ‘Machine’
1. Poorly finished dies Polish dies properly. Investigate other steels or
other materials.
2. Deep concave punches or beveled-edge Use flat punches.
faces of punches.
3. Lower punch remains below the face of Make proper setting of lower punch during
die during ejection. ejection.
4. Incorrect adjustment of sweep-off blade. Adjust sweep-off blade correctly to facilitate
proper ejection.
5. High turret speed. Reduce speed of turret (Increase dwell time).
The Causes and Remedies of Lamination related to ‘Formulation’
1. Large amount of fines in the granulation Remove some or all fines through 100 to 200
mesh screen
2. Too dry or very low moisture content Moisten the granules suitably. Add
(leading to loss of proper binding action). hygroscopic substance e.g.: Sorbitol,
Methylcellulose or PEG-4000.
3. Not thoroughly dried granules. Dry the granules properly.
4. Insufficient amount of binder or Increasing the amount of binder OR
improper binder. Adding dry binder such as pre-gelatinized
Starch, Gum acacia, powdered Sorbitol, PVP,
hydrophilic Silica or powdered Sugar.
5. Insufficient or improper lubricant. Increase the amount of lubricant or change the
type of lubricant.
The Causes and Remedies of Lamination related to ‘Machine’
1. Rapid relaxation of the peripheral regions Use tapered dies, i.e. upper part of the die bore
of a tablet, on ejection from a die. has an outward taper of 3° to 5°.
2. Rapid decompression Use pre-compression step. Reduce turret speed
and reduce the final compression pressure.
The Causes and Remedies of Chipping related to ‘Formulation’
1. Sticking on punch faces Dry the granules properly or increase
lubrication.
2. Too dry granules. Moisten the granules to plasticize. Add
hygroscopic substances.
3. Too much binding causes chipping at Optimize binding, or use dry binders.
bottom.
The Causes and Remedies of Chipping related to ‘Machine’
1. Groove of die worn at compression point. Polish to open end, reverse or replace the die.
2. Barreled die (center of the die wider than Polish the die to make it cylindrical
ends)
3. Edge of punch face turned inside/inward. Polish the punch edges
4. Concavity too deep to compress powder Reduce concavity of punch faces. Use flat
blend. punches.
The Causes and Remedies of Cracking related to ‘Formulation’
1. Large size of granules. Reduce granule size. Add fines.
2. Too dry granules. Moisten the granules properly and add proper
amount of binder.
3. Tablets expand. Improve granulation. Add dry binders.
4. Granulation too cold. Compress at room temperature.
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The Causes and Remedies of Cracking related to ‘Machine’
1. Tablet expands on ejection due to air Use tapered die.
entrapment.
2. Deep concavities cause cracking while Use special take-off.
removing tablets
The Causes and Remedies of Sticking related to ‘Formulation’
1. Granules not dried properly. Dry the granules properly. Make moisture
analysis to determine limits.
2. Too little or improper lubrication. Increase or change lubricant.
3. Too much binder Reduce the amount of binder or use a different
type of binder.
4. Hygroscopic granular material. Modify granulation and compress under
controlled humidity.
5. Oily or way materials Modify mixing process. Add an absorbent.
The Causes and Remedies of Sticking related to ‘Machine’
1. Concavity too deep for granulation. Reduce concavity to optimum.
2. Too little pressure. Increase pressure.
3. Compressing too fast. Reduce speed.
The Causes and Remedies of Picking related to ‘Formulation’
1. Excessive moisture in granules. Dry properly the granules, determine optimum
limit.
2. Too little or improper lubrication. Increase lubrication; use colloidal silica as a
„polishing agent‟, so that material does not
cling to punch faces.
3. Low melting point substances, may Add high melting-point materials. Use high
soften from the heat of compression and meting point lubricants.
lead to picking.
4. Low melting point medicament in high Refrigerate granules and the entire tablet press.
concentration.
5. Too warm granules when compressing. Compress at room temperature. Cool
sufficiently before compression.
6. Too much amount of binder. Reduce the amount of binder, change the type
or use dry binders.
The Causes and Remedies of Picking related to ‘Machine’
1. Rough or scratched punch faces. Polish faces to high luster.
2. Embossing or engraving letters on punch Design lettering as large as possible.
faces such as B, A, O, R, P, Q, G. Plate the punch faces with chromium to
produce a smooth and non-adherent face.
3. Bevels or dividing lines too deep. Reduce depths and sharpness.
4. Pressure applied is not enough; too soft Increase pressure to optimum.
tablets.
The Causes and Remedies of Binding related to ‘Formulation’
1. Too moist granules and extrudes around Dry the granules properly.
lower punch.
2. Insufficient or improper lubricant. Increase the amount of lubricant or use a more
effective lubricant.
3. Too coarse granules. Reduce granular size, add more fines, and
increase the quantity of lubricant.
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4. Too hard granules for the lubricant to be Modify granulation. Reduce granular size.
effective.
5. Granular material very abrasive and If coarse granules, reduce its size.
cutting into dies. Use wear-resistant dies.
6. Granular material too warm, sticks to the Reduce temperature.
die. Increase clearance if it is extruding.
The Causes and Remedies of Binding related to ‘Machine’
1. Poorly finished dies. Polish the dies properly.
2. Rough dies due to abrasion, corrosion. Investigate other steels or other materials or
modify granulation.
3. Undersized dies. Too little clearance. Rework to proper size.
Increase clearance.
4. Too much pressure in the tablet press. Reduce pressure. OR
Modify granulation.
The Causes and Remedies of Mottling
1. A colored drug used along with colorless Use appropriate colorants.
or white-colored excipients.
2. A dye migrates to the surface of Change the solvent system,
granulation while drying. Change the binder,
Reduce drying temperature and
Use a smaller particle size.
3. Improperly mixed dye, especially during Mix properly and reduce size if it is of a larger
„Direct Compression‟. size to prevent segregation.
4. Improper mixing of a colored binder Incorporate dry colour additive during powder
solution. blending step, then add fine powdered
adhesives such as acacia and tragacanth and
mix well and finally add granulating liquid.
The Causes and Remedies of Double Impression
1. Free rotation of either upper punch or -Use keying in tooling, i.e. inset a key
lower punch during ejection of a tablet. alongside of the punch, so that it fits the
punch and prevents punch rotation.
-Newer presses have anti-turning devices,
which prevent punch rotation.
Note:
Applications have been:

1. Oil/water emulsifier: pharmaceutical and cosmetic lotions and creams
2. Emulsion stabilizer: pharmaceutical and cosmetic creams
3. Foam stabilizer: aerosol foams
4. Suspending agent: pharmaceutical and cosmetic suspensions, recon-stitutable
pharmaceutical suspensions such as antibiotics
5. Bodying agent, thickener, opacifier: pharmaceutical and cosmetic creams, vaginal gels,
cosmetic gels.
Advantages of Tablets:
 They are easy to carry.
 They are easy to swallow.
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 They are attractive in appearance.
 Unpleasant taste can be masked by sugar coating.
 They do not require any measurement of dose i.e. their dose is accurate.
 The strip or blister packing has further facilitated the process of taking the dose by the
patient.
 Moreover it provides a sealed covering which protects the tablets from atmospheric
conditions like air, moisture and light etc.
 Some of the tablets are divided into halves and quarters by drawing lines during
manufacturing to facilitate breakage whenever a fractional dose is required
 An accurate amount of medicament even if very small amount can be incorporated.
 Tablets provide prolonged stability to medicament.
 The incompatibilities of medicaments and their deterioration due to environmental factors
are less in tablet forms.
 The cost of production is relatively low, hence economical.
 Tablets have good physical and chemical stability.
 Tablets are essentially tamper proof dosage form.
 Tablets are the unit dosage form and they offer the greatest capabilities of all oral dosage
forms.
 Their cost is lowest of all dosage forms
 They are the lightest of all dosage forms.
 They are in general the easiest and cheapest to package and transport of all oral dosage
forms.
 Identification of the products of the tablets is potentially the simplest and cheapest, requiring
no addition process.
 Swallowing of the tablets is very easy especially when intake of tablet is through any
suitable liquid, like water.
 Handling of the solid dosage form i.e. tablet is very easy. No special prevention or
precautionary measures are required for handling the tablets.
 The chances of microbial or bacterial attack are very less for dry, solid dosage form i.e.
tablet as compared to syrups.
 Tablets are better suited to large scale production than other unit oral forms.
 Tablets are one of those oral, solid dosage forms to whom coating can be applied to improve
palatability or reduce the incidence of gastric irritation.
Advantages Afforded to Manufacturer:

1- Simplicity
2- Economy of preparation
3- Stability
4- Convenience in packaging, shipping and dispensing
Disadvantages of Tablets:
 Irritant effects on the GI mucosa by some solids (e.g., aspirin)
 Possibility of bioavailability problems resulting from slow disintegration and dissolution

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 Some patients, particularly the children and seriously ill, may experience difficulty in
swallowing tablets. (If the tablet is too large, reformulation as two smaller units each
containing half the required dose, may minimize the problem in some case)
 One of the disadvantages of tablets is that demulcent action of linctuses cannot be effectively
obtained with a tablet.
 Drugs with poor wetting, low dissolution and optimum absorption high in the gastro
intestinal tract may be difficult to formulate as a tablet that will provide adequate or fuel
drug bioavailability.
 Bitter tasting drugs, drugs with an objectionable odour, or drugs that are sensitive to oxygen
or atmospheric moisture may require capsulation prior to compression or tablets may require
coating.

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Pharmaceutics – II (Dosage Form Science):

CAPSULES DOSAGE FORM

1. Hard Gelatin Capsules

HARD GELATIN CAPSULE

Types of Hard Gelatin Capsules:

Prepared by: Muhammad Muneeb

Hard Gelatin Capsules for Human Use:

 000 _______ 1000mg

 Imprinting (a word or company name)

HARD GELATIN CAPSULE MANFACTURING STEPS

Prepared by: Muhammad Muneeb

Prepared by: Muhammad Muneeb

Extemporaneous filling of a small number of capsules is possible by spreading the powder to be

Prepared by: Muhammad Muneeb

SEALING AND LOCKING

Some Modern Uses of Hard Gelatin Capsules:

SOFT GELATIN CAPSULES

ROTARY DIE PROCESS:

 Liquid gelatin flowing from an

Prepared by: Muhammad Muneeb

RECIPROCATING DIE PROCESS

Soft gelatin capsules are especially important to contain:-

Prepared by: Muhammad Muneeb

PHYSICAL STABILITY OF CAPSULES

Prepared by: Muhammad Muneeb

Prepared by: Muhammad Muneeb

Pharmaceutics – II (Dosage Form Science):

Shape and Size:

Prepared by: Muhammad Muneeb

5. Granules Result after Wet Granulation:

Prepared by: Muhammad Muneeb

A. IF SMALL DOSE OF DRUG IS REQUIRED

B. IF DOSE OF DRUG IS LARGE:

Prepared by: Muhammad Muneeb

Examples of Materials used for Enteric Coating:

1. Wet method which is further subdivided into;

A. SIMPLE WET METHOD:

B. FLUID BED PROCESSING:

Prepared by: Muhammad Muneeb

TABLET GRANULES DOSAGE FORM GRANULES

It consists of grains which show It consists of grains that are as uniform as

Prepared by: Muhammad Muneeb

Effervescent Granules are produced by two general methods:-

Effervescent Granules have following significances:

1. They have effective effervescence.

Prepared by: Muhammad Muneeb

 They are available in amorphous or crystalline form.

 Powder used as dosage forms may be prepared from:

Powders and Particle Size:

 In order to standardize particle size of a powder, USP employs descriptive terms

Particle size can influence:

 DISTRIBUTION: Uniform distribution of a drug substance in a powder mixture form to

 NONGRITTINESS: Lack of grittiness of solid particles in dermal ointments, creams,

Determination of Particle Size:

Prepared by: Muhammad Muneeb

 Rapid dissolution produces high blood levels in shorter time.

 Drugs which deteriorate upon exposure to atmospheric conditions cannot be dispensed

ACCORDING TO THE NO. OF ACTIVE INGREDIENTS PRESENT:

 Hyoscine hydrobromide powder used as an anti-emetic.

 This dosage form contains more than one active ingredient.

 Compound bismuth powder

 Compound kaolin powder.

ACCORDING TO MODE OF DISPENSING: