25/09/2014

SUPPOSITORY

Page 1

SUPPOSITORY
It is solid dosage form meant to be
inserted into Body cavity like rectum ,
urethra, vagina, where they melt or soften
to release the drugs and produce their
local or systemic effect.

It is comes under semi solid preparation

because it is prepared by melting all
ingredients (bases and other additives
along with active ingredient).

All types of suppositories are melt at

normal body temperature after
introducing in body cavity and produce
their effect. Page 2

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ADVANTANGE OF SUPPOSITORY
It is the alternated dosage form for drugs
which have less bioavailability when it is
taken orally.
Drugs having bad odour and taste can be
used in suppository form.
It is suitable for unconscious patients
which can not taken drugs orally.
It is suitable for drugs which produce
irritating effect in GIT.
It is suitable for infants and old people
who find difficulty in swallowing of drugs.
It is suitable for the drugs which are
destroyed by portal circulation.
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DISADVANTAGE OF SUPPOSITORY
The manufacturing process is more
difficult as compare other formulation.
The drugs which cause irritation to
mucous membrane can not be
administrated by this form.
The most important problem is storage
condition because it stored at low
temp.(10-20 0c ). Other than the bases get
liquefied.
Leakage problem is also most critical
problem along with suppository after
introducing in body cavity at elevated
temperature.

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TYPES OF SUPPOSITORY

(A)RECTAL SUPPOSITORY-

It is inserted in the rectal .

The weight of suppository used in

children is about 1g and in adult
about 2g.

The shape of suppository used in rectal

is torpedo shape. The length is about 3
cm.
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(B) URETHRAL SUPPOSITORY

The weight of this type suppository is

about 2g and 60-75 mm long in Females.

Those intended for males weigh 4 gm

each and are 100-150 mm long.

It is available in pencil shape.

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(C) VAGINAL SUPPOSITORY

It is in oviform shape.

It is about 3-5g in weight.

It is contains the drugs which are used in

treatment of the infections of female
genitourinary tract and meant for
contraception.

It is contains the combination of

polyethylene glycol of different molecular
weights as suppository bases.
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(D) NASAL SUPPOSITORY

These suppository are meant for
introduction into nasal cavity.
It is about 1g in weight.
The glycero- gelatin is used as
suppository bases.

(E) EAR CONE

It is also known as AURINARIES.
These are meant for introduction into the
ear.
It is cylindrical in shape.
It is about 1g in weight.

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VARIOUS SHAPES OF SUPPOSITORY

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FORMULATION OF SUPPOSITORIES
(A) SUPPOSITORIES BASES-

IDEAL PROPERTIES OF SUPPOSITRIES

BASES-
The following properties should be required
for bases---
Bases should be exist in solid form at
room temperature.
It should not irritate and produced
inflamed sensation in body cavity.
It should be stable during storage
condition , No change in colour, shape ,
odour.
It should retain hardness and shape
during manufacturing and handling. Page 10

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IDEAL PROPERTIES OF SUPPOSITRY BASES

It should not reacts with drugs and additives.

It should have good emulsifying and wetting

property.

It should have acid value less than 0.2 or

zero.

It should have iodine value less than 7.

It should have sponification no. range

between200-245.
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(1) HYDROPHILIC BASES

(A) WATER DISPERSIBLE BASES-

These are the mixture of non ionic

surfactants which are chemically related
to polyethylene glycol.

These are used alone or in combination

with other type of bases.

Cellulose derivatives like

methylcellulose, sod.carboxymethyl
cellulose are also comes under this
class.

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Advantages
They are suitable for both water soluble
and oil soluble drugs.
They do not support the growth of
microbes in the preparation.
They can be stored at elevated
temperature.

Disadvantages-

This types of bases are interact with few

drugs and alter the bioavailability of
these drugs.

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EXAMPLES

Polyoxyethylene sorbitan fatty acid

ester(TWEENS)

Polyoxyethelene stearates(MYRIS)

Sorbitan fatty acid esters(SPANS)

Combination of Tween 61(60%) and

Tween 60(40%)

Combination of Tween 61 (85%) and

glyceryl monostearate (15%)
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(B) WATER SOLUBLE BASES

(1) GLYCERO-GELATIN-
This occurs as a gels
It is a mixture of gelatin, glycerol, and
water.
According to BP the composition of the
bases –
GELATIN- 14% w/w
GLYCEROL– 70% w/w
WATER– QS

For gets a stiff mass , the quantity of

gelatin should be increased to 32.5% and
reduced the glycerol to 40%.
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PREPARATION OF GLYCERO-GELATINE
BASES

GLYCEROL WATER GELATINE

GLYCERO-GELATINE BASES

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ADVANTAGES

Suppository prepared by glycero-gelatin

bases are strong and translucent unlike
cocoa butter suppositories.

This base is disperse slowly in the body

cavity fluids and provides prolonged
release and action of drugs.

DISADVANTAGES-

It absorbs moisture and promotes

microbial growth , so this reason
preservatives are used . Page 17

DISADVANTAGES

The bases are show incompatibility with

protiens prescipitants due to the gelatin

It causes dehydration and irritation of

rectal mucosa

It exerts undesirable laxative action.

It requires special storage condition at

about 10-15 0c.

Handling and manufacturing of these type

of suppository are difficult. Page 18

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(2) POLY ETHYLENE GLYCOL(POLYGLYCOL)

It is also called as PASTONALS
(GERMANY).
CARBOWAXES(U.S)
They are long chain polymers of ethylene
oxide.
They occur in liquid and solids.
Liquids have mol.weight about 200-600.
Solid have mol.weight about more than
1000.
They are also called as macrogols.
They are the mixture of two or more
grades of macrogols used as
suppository bases.
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EXAMPLES

PEG 4000- 33 parts

PEG 6000- 47 parts
PURIFIED WATER- 20 parts

FOR HARD SUPPOSITORY

PEG 1000- 75 parts
PEG 4000- 25 parts

FOR SOFT SUPPOSITORY

PEG 1000- 96 parts
PEG 4000- 4 parts

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ADVANTAGES

This base is thermostable.

It does not get degraded or hydrolysed.

It does not support microbial growth.

It dose not move out from body cavity

after introducing.

It has good water absorbing capacity.

It is chemically stable.
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DISADVANTAGES
It is susceptible to rancidification,so it
should be stored in dry place away from
light.
It melt easily in warm weather,so it should
stored in cool place in warm season.
Large quantities of water can not be
incorporated into the bases.So emulsifier
such as tween 61 (6-10%) are useful to
increase the absorption of water.
The physical characteristics of the bases
are change from batch to batch.
Some times leakage may be occur after
introducing in body cavity.

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(2) LIPOPHILIC BASES

(a) COCOA BUTTER

It is natural triglyceride.
Among all fatty acid about 40% are
unsaturated fatty acid .
It can exist in more than one crystalline
form or exhibits polymorphism.
At room temperature ,it is yellowish-white
with a paints,chocolate like odour.
It consists of a mixture of ester of oleic
acid,palmatic acid,stearic acid and other
fatty acid with glycerol.

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ADVANTAGES

It is liquified readily on warming and

sets rapidly on cooling.

It has emollient effect which is useful to

relieve inflammation.

It shows good release of water soluble

drugs.

It does not cause irritation in mucous

membrane.

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DISADVANTAGES
It is susceptible to rancidification ,so it
should be stored in dry place away from
light.
It gives soft suppository when
formulated along with chloral hydrate ,
phenol, volatile oil, which have lower
melting point.
The physical property of the base is vary
from batch to batch.
It required extra lubricant during poring
in holder.
Some times leakage may be occur.

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(B) ANTI OXIDANTS

It is protect the drugs and bases from

getting degraded due to oxidation.
These are commonly used in all types of
suppositories.
EXAMPLES-
Ethyl or propyl gallate
Ascorbic acid
Butylated hydroxy anisole (BHA)
Butylated hydroxy toluene (BHT)
Hydroquinone
Tocopherol

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(C) EMULSIFYING AGENTS

These are increase the water absorbing

capacity of fatty bases.

EXAMPLES

Poly sorbates (TWEEN 61)

Wool alcohol

Wool fats

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(D) HARDENING AGENTS

These are involved in those formulation

where the melting point of the bases is
decrease by the drugs.

These are the agents which are used to

bring the melting point to normal.
EXAMPLES
Beeswax
Macrogols at high molecular weight.

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(E) PRESERVATIVES

These are the agents which are used in

prevent the growth of microbial in
suppository which contains water
soluble bases.

EXAMPLES

Chorocresol

Methyl paraben

Propyl paraben
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(F) THICKENING AGENTS

These are the agents which are used to
increases the viscosity of molten bases
and prevent sedimentation of suspended
in solid bases.

EXAMPLES

Aluminium monostearate
Colloidal silica
Magnisium stearate
Steary alcohol

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(G) PLASTICIZERS
These are the agent which are used to
improved flexibility of suppositories.
It is also used to make the less brittles
to suppositories.

EXAMPLES
Castor oils
Glycerine
Glycol
Tween 80
Tween 85

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METHODS OF PREPARATION OF
SUPPOSITORIES

MOLDS USED IN PREPARATION OF

SUPPOSITORIES-
Molds used in preparation of
suppositories are the metals devised with
different shape.
It is consists of two or more parts which
are joined with a screw.
In side the molds the cavities are made
up of aluminium , brass, stainless steel ,
plastics.
Molds have different capacities like
1,2,4,8gm.
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Mold

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PLASTICS MOLDS

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CALIBRATION OF THE MOLDSCC

The first step is to prepare molded

suppositories from base material alone.

The suppository's combined and average

weight is recorded.

To determine the volume of the mold, the

suppositories are melted in a calibrated
beaker, and the volume of the melt is
determined.
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LUBRICANTS USED IN MOLDS

Cocoa butter and glycero-gelatine bases
are required lubrication of molds.
This is prevent sticking of bases to the
wall of molds cavity.
It is also useful in easy removal of
suppositories from the molds.
The lubricants are form a film between
the wall of mold cavity and base of
suppositories so it prevent adhering of
bases to the molds.
The nature of lubricants should be
different from nature of bases.

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EXAMPLES

(1) FOR COCOA BUTTER BASES

ALCOHOL(90%)- 50ml
GLYCEROL - 10ml
SOFT SOAP - 10 gm

(2) LIQUID PARAFFIN

(3) ARACHIS OILS

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MANUFACTURING OF SUPPOSITORIES
Hand molding
Automatics Machine Molding
Compression Molding
Heat Molding

1) HAND MOLDING-
Hand molding is useful when we are
preparing a small number of
suppositories.
It is suitable for thermo labile drugs.
It is more economical methods.
It is more time consuming and not
uniformity process.
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STEPS INVOLVED IN HAND MOLDING

The drugs and other additives are made

into a fine powder .

It is incorporated into the suppository

base by kneading with it or by trituration
in a mortar.

Then these masses are rolled into the

shape of a cylindrical rod on the rolling
tile in presence of lubricants to prevent
the adherence of masses.

Then cut the rods and made one end to

Page 39
pointed.

DRUG+ADDITIVES FINE POWDER

MIXED IN BASES

APPLY LUBRICANTS ON ROLLING TILE

ABOVE MASSES ARE ROOLED IN

CYLINDRICAL SHAPE

CUT THE RODS

PACKED

STORED
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(2) AUTOMATIC MACHINE MOLDING

All the operations in pour molding are
done by automatic machines.
Using this machine, up to about 10,000
suppositories per hour can be produced.
By this the rate of production of
suppositories is more higher than hand
molding.
In this ,there are no chance of air
entrapment and contamination of
suppositories.
In this ,if any mass deposited in mold is
not removed during cleaning, so produce
overweight suppositories with mold
marks.
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There are two types of machines used they

are following---
(a) Rotary Machine-
The rate of production of suppositories
are about 3500-6000/hr.
This machine consists of a turn table in
which metal molds are fitted.
This table rotates sequentially, the mold
gets filled with drug , additives, bases
and cooled and ejects the suppositories.
Before mass filled in mold ,the lubricant
are apply in mold wall.
The excess mass is removed by the
scraping unit.
The cooling system results the
solidification of suppositories. Page 42

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After the cooling the mold is moves

towards ejection station , it consists of a
stainless steel rod which push out the
suppositories from molds.
Then completed the ejection process , the
empty molds are again moves towards
the filling unit for further processes.

STEPS INVOLVED IN PROCESS AS

FOLLOWING

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DRUG+ADDITIVES FINE POWDER

MELT BASES + POWER

HOPPER

LUBRICATED THE MOLDS

FILL ABOVE MIXTURE IN MOLD

COOLING SYSTEM

EJECTION SYSTEM

PACKED STORED Page 44

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(b) LINEAR MACHINE

It is similar to rotary machine.

Except the rate of production is more

higher than rotary machine about
10000/hr.

All steps involved is similar to rotary

machine.

There is no chance of air entrapment

and contamination of suppositories as
similar to rotary machine.
The rate of production is higher than
rotary machine. Page 45

(3) COMPRESSION MOLDING

CONSTRUCTION- The compression
machine consists of a cylinder, piston ,
molds, and a metallic stop plate at the
bottom.

WORKING- When placed the mass in

cylinder and apply the pressure .
Then mass fulfill in mold move and s
remove the suppositories and keep them
in cool placed.
After cooling release them from
compression machine and packed .

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PROCEDURE
DRUG+ADDITIVES FINE POWDER

MIXED WITH BASES

LUBRICANTS APPLY IN MOLDS

PLACED THE MASSES IN CYLINDER

APPLY PRESSURE

RELEASE SUPPOSITORY

COOLED PACKED STORED

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ADVANTAGE-

It is suitable for thermolabile drugs

because in this method no heat is
required.

Rate of production is more.

DISADVANTAGE-

The main disadvantage is air

entrapment occurs during production
so oxidation takes place in suppository.

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(4) HEAT MOLDING

In this process the bases are melted and
the drugs , additives are mixed in bases.

The following methods are involved in

this process-

(a) Melting the bases

(b) Incorporation of the drugs and other
additives
(c) Filling of mold
(d) Cooling and collection of suppositories

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Incorporation of drug and additives-

the drugs and additives are in solid form ,

they are converted in fine powder and
mixed properly on a warm tile.

Triturate the ingredient on warm tile with

the sufficient water.

These above liquid are mixed in melted

bases in half amount after mixing , then
added remaining liquid in bases.

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FILLING OF MOLDS-

First the lubricants are apply in molds.

Then the above masses are introducing

in molds.

During introducing the masses in

molds the stirring should be done to
prevent the sedimentation of insoluble
solids , if they present.

Overfilling is required to prevent the

depression in suppositories.

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COOLING AND COLLECTION OF

SUPPOSITORIES

After the2-3 min . the mass just sets.

Then remove the excess mass with warm
spatula.

Cool the suppositories for 10-15 min. in

refrigerators.

Then open the mold and collect the

suppositories and packed.

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MELTING THE BASES DRUGS

FINE POWDER

TRITURATE
WITH WARM WATER

LIQUIDS

MIXED ½ PARTS OF LIQUIDS

MIXING PROPER

ADD REMAINS LIQUIDS

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CONT……

APPLY THE LUBRICANTS IN MOLD

OVERFILLING OF MASSESIN MOLDS

REMOVE THE EXTRA MASSES

COOLING (10-15MIN)

OPEN MOLDS

PACKED

STORED Page 54

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PACKING OF SUPPOSITORIES

(1) DISPOSABLE MOLDS-

These are meant for packing the
suppositories.
These are made of plastics or aluminium
foil.

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(2) MODERN PACKING MACHINE

It is consist of roll of packing material

which cut in the required size and rolled
around each suppositories.

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• STORAGE CONDITION

It is stored at 10-15 0c

Used air tight container

The suppositories with cocoa butter

stored at < 30 0c.

The suppositories with glycero-gelatin

stored at < 35 0c.
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EVALUATION OF SUPPOSITORIES

Test of appearance(size , shape)

Test of physical strength

Test of dissolution rate

Test of melting range

Test of softening time

Test of uniformity of drug content

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STABILITY PROBLEMS OF
SUPPOSITORIES
BLOOMING-
During storage , cocoa butter
suppositories sometimes show
deposition of white powder on the
surface.
This result in suppositories of
disagreeable appearance.
HARDENING-
During storage , the suppositories made
of fatty bases become hard.
I is occurs due to crystallization of bases.
This also effect the melting and rate of
absorption of drugs. Page 59

THANKS

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