Professional Documents
Culture Documents
Powder
Powder
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
D16M137
PUCP
There are two types of capsules available
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.
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.
Manufacture:
Some special techniques used in hard gelatin capsule manufacturing are
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
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
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
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 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.
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.
Prepared by: Muhammad Muneeb
D16M137
PUCP
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.
Materials to be filled:
They may be employed to contain:
Liquids
Suspensions
Pasty materials
Dry powders
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.
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.
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
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.
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.
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:
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.
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.
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:
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.
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.
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.
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:
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
Prepared by: Muhammad Muneeb
D16M137
PUCP
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:
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:
Drugs are prepared in different forms and shapes but many of them are prepared by using
powder in one way or the other.
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).
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.
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.
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.
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
As a drying agent
As adsorbent of bacteria, bacterial toxins, poisons , gases etc
It is cheap and wastage is minimum
DISADVANTAGES OF POWDERS:
CLASSIFICATION OF POWDERS:
1. Simple powders
Prepared by: Muhammad Muneeb
D16M137
PUCP
2. Compound powders
SIMPLE POWDERS:
This dosage form consists of one active ingredient mixed with some inert substance i.e.
lactose, starch.
EXAMPLE:
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:
Prepared by: Muhammad Muneeb
D16M137
PUCP
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.
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:
It is used for potent drugs or for drugs to be used at controlled rate and dosage.
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.
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.
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
Prepared by: Muhammad Muneeb
D16M137
PUCP
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.
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.
A. 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.
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:
DISADVANTAGE:
It is tedious and expensive process and requires accurate and precise machinery.
The mode of operation of repeat action coated tablets and their limitations are based on
uncontrolled and unpredictable gastric employing.
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:
Compressed tablets may be coated with colored or uncolored sugar layer. This coating is
water soluble and quickly dissolves after swallowing.
ADVANTAGES:
DISADVANTAGES:
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.
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.
i. Buccal Tablets
ii. Sublingual Tablets
iii. Troches and Lozenges
iv. Dental Cones
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.
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.
Prepared by: Muhammad Muneeb
D16M137
PUCP
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.
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.
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.
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.
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).
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.
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.
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.
Granules may be dried in thermostatically controlled ovens that constantly record the time,
temperature, and humidity.
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.
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.
A. Slugging
B. Roller Compactation
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
DISADVANTAGES
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.
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,
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.
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.
Mechanical Release
Weight Content Visual
Strength Profile
Variation Uniformity defects
Related Altered
Hardness Friability
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.
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
v. Hardness Variation:
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.
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
Dissolution Test:
In vitro dissolution testing of solid dosage forms is important for a number of reasons:
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:
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.
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.
Advantages of Tablets:
They are easy to carry.
They are easy to swallow.
Prepared by: Muhammad Muneeb
D16M137
PUCP
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.
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