Suppository - Types & Formulation

Suppository - types, when to use, formulation and problems arising with Suppository

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SUPPOSITORIES

The term suppository comes from Latin and means "to place under."
Suppositories are solid or semisolid dosage form of medicament designed for insertion into body
cavity other than mouth like rectum, vagina or urethra cavity where they melt, dissolve or disperse to
release the medicament from suppository base and exert a local or systemic effect.

They are available in different sizes, shapes and weights. After insertion they melt or soften at
body temperature, whereas vaginal suppositories sometimes called as pessaries, are also made as
compressed tablets that disintegrate in body fluids.

• Solid or semi-solid dosage form
• Intended for insertion into body orifices ( Rectum, Vagina, Urethra )
• They melt, soften or dissolve in the body orifices and exert local or systemic effect.

Advantages of Suppositories
Over Oral Drug Administration:
1. Avoid first pass metabolism
2. Avoid any Gastrointestinal irritation
3. Beneficial for -
 Patients suffering from severe nausea and vomiting
 Babies and old age
 Post-operative patient
 Unconscious patient.
Over parenteral drug administration:
1. Self medication
2. Safe and painless form of administration.
3. No need of skilled healthcare personnel.
4. Localized action with reduced systemic side effects
Related to Drug itself :
1. Drugs which are not stable at Gastrointestinal pH
2. Drugs which are liable to enzymatic degradation in the GI tract
3. Drugs with an unacceptable taste
4. Prolonged drug action can be achieved
5. larger doses can be administered.
Over Vaginal Tablets:
1. Dissolves faster
2. Total bioavailability achieved
3. No residue remains like tablet
4. No need of applicator
5. Non-itching
6. Highly beneficial in haemorrhoids and vaginal infections .

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Disadvantages of Suppositories
1. Local Mucosal irritation
2. First Pass Metabolism due to upward movement
3. Not suitable for patients with diarrhoea.
4. Leakage of Suppositories
5. Poor patient acceptability
6. Sometimes incomplete absorption
7. Drug absorption is slow in comparison to oral or intravenous administration.
8. Inter and intra subject variation
9. Proctitis
10. GI state affects absorption
11. Embarrassment to the patients
12. Large scale production difficult and costly
13. Shelf life (Stringent [strict & precise] storage conditions)


‘Rectal administration should certainly not be the route of first choice but can in certain
circumstances be of great advantages to the patient’
Arguments for choosing the rectal route for drug administration include:
1) The patient is not able to make use of the oral route.
This may be the case when the patient has GIT infection, is nauseous, or is postoperative (when the
patent may be unconscious). Furthermore, the very young, the very old or mentally disturbed may
more easily use the rectal than the oral route.
2) The drug under the consideration is less suited for oral administration.
This may be so in cases where oral intake results in GI side effects, also the drug insufficiently stable
at the pH pf GIT or liable to degradation in GIT or during the first pass effect after absorption. Also,
the drugs with an unacceptable taste and certain drugs that are the candidates for abuse, as in
suicide can be considered and administered rectally.

Besides these apparent advantages, the rectal route also has several drawbacks-
1) Slow and sometimes incomplete drug absorption has been reported.
2) The development of proctitis has been reported.
3) Upward movement of suppository from local site of rectum can increase the
first pass metabolism.
4) Insertion of suppository may be problematic.
5) It causes embarrassment to the patient.
6) Patients acceptability and compliance is poor.

It can thus be concluded that `rectal administration should certainly not be the route of first choice but
can in certain circumstances be of great advantages to the patient`.

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Why medicaments are prescribed in suppositories ?
Medicaments are prescribed in suppositories for three reasons:
1. To exert a direct or local action on the rectum
Local action is desired in the case of pain and itching mostly due to occurrence of hemorrhoids. Locally
active drugs which are used include astringents, antiseptics, local anaesthetics, vasoconstrictors and
anti-inflammatory agents.
2. To promote the evacuation of the bowel
Some laxative drugs, e.g. glycerol and Bisacodyl, exert their effect by irritating the rectum.
3. To produce a systemic effect by the drug under the consideration is less suited for oral
administration.
Suppositories are convenient mode of administration of drugs which irritate GIT, cause vomiting and
destroyed in acidic pH of the gastric juice of stomach. The patients who are GIT infected, unconscious,
mentally disturbed or cannot tolerate oral medication, is not able to make use of the oral route. In that
case medicaments are formulated as suppositories for particular treatment value.

TYPES & SIZE OF SUPPOSITORIES
Size Of Suppositories
0 For Children
1,2 & 3 For rectal use
4 Pessaries
A & B Nasal & urethral bougies
Types Of Suppositories

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Shape Of Suppositories


RECTUM PHYSIOLOGY
In order to understand the mechanisms of drug absorption from rectum and vagina it is important to
know the anatomy and physiology of the region.
 Terminal 15-19 cm of large intestine (LI)
 Rectal Fluids -> no buffering capacity
 1. 2 - 3 mL
 pH 6.8
 Mild environment / drug can change pH
 LI function absorb H2O and electrolytes
 Low surface area -> poor absorption compares SI

RECTAL BLOOD CIRCULATION
Main blood supply- superior rectal artery.
Blood return by 3 blood veins-
1. Superior hemorrhoidal vein
2. Middle hemorrhoidal vein
3. Inferior hemorrhoidal vein

1. Superior hemorrhoidal vein
- Inferior mesenteric vein > Hepatic
portal vein > Liver
2. Middle and inferior hemorrhoidal vein
- Iliac vein > inferior vena cava
 Drug goes directly into systemic
circulation
 No first pass metabolism by liver
 Drug avoids stomach and digestive enzymes

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Patient counselling - don't place too high in rectum.
Location Of Suppository


Suppositories provide direct access to the systemic circulation, efficiently bypassing the portal
circulation and the liver metabolism on the first pass. It is a fact that the lower and middle hemorrhoidal
veins bypass the liver and do not undergo first-pass metabolism. Therefore, suppositories can deliver
the drug rapidly to the lower and middle hemorrhoidal veins for absorption. So, it should be advisable
to position the suppository in middle and lower part of the rectum for better absorption.

FORMULATION OF SUPPOSITORIES
Problems In Formulation Of Suppositories -
• Water content
• Viscosity
• Drug-Excipient interaction
• Lubrication of mould
• Brittleness
• Rancidity
• Packaging

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PROBLEMS IN FORMULATION OF SUPPOSITORIES
1. Water in suppositories
Formulators do not like to use water for dissolving drugs in suppositories for the following reasons:
a) Water causes oxidation of fats.
b) If the suppositories are manufactured at a high temperature, the water evaporates, the drugs
crystallize out.
c) Absorption of water soluble drugs is enhanced only if the base is an oil – in – water emulsion
with more than 50% of the water in the external phase.
d) Drug excipient interactions are more likely to happen in the presence of water.
e) Bacterial contamination may be a problem, so we may be forced to add a preservative.
2. Hygroscopicity
• Glycerogelatin suppositories lose moisture in dry climates and absorb moisture in humid
conditions
• The hygroscopicity of polyethylene glycol bases depends on the chain length of the molecule
• As the molecular weight of these ethylene oxide polymers increases the hygroscopicity decreases
3. Drug-excipient interactions
a) Incompatibilities exist between polyethylene glycol base and some drugs.
b) Sodium barbital and salicylic acid crystallize out of polyethylene glycol.
c) High concentrations of salicylic acid soften polyethylene glycol to an ointment like consistency.
d) Penicillin G is stable in cocoa butter and other fatty bases. It decomposes in polyethylene
glycol bases.
4. viscosity
A) when the base has low viscosity, sedimentation of the drug is a problem.
B) 2% aluminium monostearate may be added to increase the viscosity of the base
C) cetyl and stearyl alcohols or stearic acid are added to improve the consistency of suppositories.
5. Brittleness
a) Cocoa butter suppositories are elastic, not brittle
b) Synthetic fat bases are brittle
c) This problem can be overcome by keeping the temperature difference between the melted
base and the mould as small as possible
d) Materials that impart plasticity to a fat and make them less brittle are small amounts of Tween
80, castor oil, glycerine or propylene glycol
6. Density
Density of the base, the drug, the volume of the mould and whether the base is having the property of
volume contraction are all important. They all determine the weight of the suppository
7. Lubrication of moulds
Some widely used lubricating agents are mineral oil, aqueous solution of SLS, alcohol and tincture of
green soap. These are applied by wiping, brushing or spraying

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8. Volume contraction
On solidification the volume of the suppository decreases. The mass of the suppository pulls away from
the sides of the mould. This contraction helps the suppository to easily slip away from the mould,
preventing the need for a lubricating agent.
Sometimes when the suppository mass is contracting, a hole forms at the open end. This gives an
inelegant appearance to the suppository. Weight variation among suppositories is also likely to occur.
This contraction can be minimized by pouring the suppository mass slightly above its congealing
temperature into a mould warmed to about the same temperature. Another way to overcome this
problem is to overfill the moulds, and scrape off the excess mass which contains the contraction hole.
9. Displacement value
The volume of suppositories from a particular mould will be constant but the weight will vary because
the densities of the medicaments usually differ from the density of the base, and hence the density of
the medicament will affect the amount of the base required for each suppository
10. Weight and volume control
Various factors influence the weight of the suppository, the volume of the suppository and the
amount of active ingredient in each suppository.
They are:
1. Concentration of the drug in the mass
2. Volume of the mould cavity
3. The specific gravity of the base
4. Volume variation between moulds
5. Weight variation between suppositories due to the inconsistencies in the manufacturing
process.
The limit for the weight variation in suppositories is 5%.
11. Rancidity
The unsaturated fatty acids in the suppository bases undergo auto oxidation and decompose into
aldehydes, ketones and acids. These products have strong, unpleasant odours.
The lower the content of unsaturated fatty acids in a base, the higher is its resistance to rancidity.

FORMULATION
Suppositories are formulated in different shapes and sizes usually 1- 4g. Their drug content varies
widely from less than 0.1% up to almost 40%. Generally, the suppositories consist of a vehicle or base
in which the drug is incorporated and in some cases additives are co-formulated.
What type of drugs can be used as suppository?
Drugs -
1. Should have sufficient absorption in particular body cavity (if for systemic use)
2. Best suited for drugs undergoing first pass metabolism, degrade in GI fluids or irritate
the GI mucosa

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3. Should be easily dispersible or soluble in the base
4. Should be soluble homogenously
5. should not have more affinity for the base so that it wouldn't get released
6. Particle size should be less to improve bioavailability and decrease irritation
7. Density and solubility of the drug should ensure minimum usage of base and formation
of smaller suppositories
8. Drug should be compatible and stable in base and at processing conditions
SUPPOSITORY BASES
Since suppositories are special solid dosage form of medicament, so it is formulated in such a way that
they will retain its shape, solidity and firmness during storage and administration but melt or dissolve
in the cavity fluid to release the medicament when inserted into the body cavity. Therefore, the material
used as suppository bases must impart these properties and also fulfill the other formulation
requirements.
An ideal suppository base should have the following properties:
• Melt at body temp.
• Dissolve or disperse in body fluids
• Release any medicament readily
• Retain its shape when handled
• Non-toxic & non-irritant to mucous membrane
• Stable on storage
• Compatible with all medicaments
• Stable above its melting point
• Easily mouldable
• Should not adhere to the mould
There is no single suppository base which possesses all the qualities of an ideal suppository base. So,
it becomes necessary to use more than one suppository base during the preparation of suppositories.

TYPES OF SUPPOSITORIES BASES
Based on their physical properties, suppository bases fall into the following categories-
a. Fatty bases
i. Cocoa Butter
ii. Synthetic fats
iii. Proprietary synthetic bases
b. Water soluble or water miscible bases
i. Glycero-gelatin
ii. Macrogols

FATTY BASES
Cocoa Butter (Theobroma Oil)
Properties-
a) It is the most widely used suppository base. It solid at room temperature but melts at body
temperature to release the medicaments for rapid absorption.

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b) It is naturally occurring triglyceride with oleopalmitostearin and oleodistearin glyceride chain
and contains 40% of the unsaturated fatty acid.
c) It is yellowish white solid, brittle fat, which smells and tastes like chocolate. Ready liquefaction
on warming and rapid settling on cooling.
d) Its melting point lies between 30-35
o
C (86-95
o
F), its iodine value is between 34 and 38 and its
acid value is no higher than 4.
e) It satisfies the requirements for an ideal base – non-reactive, and melts at body temp. Miscible
with many ingredients.

Disadvantages of Cocoa Butter
• Polymorphism
• Adherence to mould
• Low softening point
• Melting point reduction
• Deterioration during storage
• Poor water absorbing capacity
• Leakage from the body

Polymorphism
 Polymorphism in cocoa butter is observed due to high proportion of unsaturated triglycerides.
 The formation of various forms of cocoa butter depends on the degree of heating, on the
cooling process and on the conditions during this process.
 Each form of cocoa butter has different melting point and drug release rates.

Cocoa Butter Exits in Four Crystalline State
• α form
 melts at 24
o
C
 Obtained by suddenly cooling melted cocoa butter to 0
o
C.
• ß form
 Crystallizes out of the liquefied cocoa butter with stirring at 18 to 23
o
C.
 Its melting point lies between 28 and 31
o
C.

• ß` form (Standard & more stable form)
 changes slowly into the stable ß form.
 Melts between 34 and 35
o
C.
 Change is accompanied by volume contraction.
• γ form
 melts at 18
o
C
 Obtained by pouring a cool cocoa butter, before it solidifies, into
a container which is cooled at deep freeze temp.

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Particular attention must be given to two factors when preparing suppositories with cocoa
butter base.
First, this base must not be heated above 35°C (95°F) during manufacturing because cocoa butter is
a polymorphic compound and if overheated will convert to a metastable structure that melts in the 25°
to 30 °C (77° to 86°F) range. Thus, the finished suppositories would melt at room temperature and not
be usable. The second factor is the change in melting point caused by adding certain drugs to cocoa
butter suppositories. For example, chloral hydrate and phenol tend to lower the melting point.
So, It may be necessary to add spermaceti or beeswax to raise the melting point of finished
suppositories back to the desired range.
Adherence to the mould
• Cocoa butter does not contract sufficiently on cooling to loosen the suppositories in the
mould.
• Sticking may be overcome by adequate lubrication.

Softening point too low for hot climates
• To raise the softening point, white bees wax may be added to Theobroma oil suppositories
intended for use in tropical and subtropical countries.

Melting point reduced by soluble ingredients
• Phenol and chloral hydrate have a tendency to lower the melting point of cocoa butter.
• So, solidifying agents like beeswax (4%) may be incorporated to compensate for the softening
effect of the added substance.

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Rancidity on storage
• Due to the oxidation of unsaturated glycerides.
Poor water-absorbing ability:
• Improved by the addition of emulsifying agents.
Leakage from the body:
• Sometimes the melted base escapes from the rectum or vagina, so, it is rarely used as a
pessary base.
Expensive
• Relatively high cost

Why cocoa butter is not used in the preparation of pessaries?
It is considered a most suitable base for rectal suppositories but not suitable for pessaries because after
melting it has a tendency to leak out of the body cavities and also it is immiscible with mucous
secretions.
Synthetic Fats
• To overcome the disadvantages of Theobroma oil synthetic substitutes were searched.
• Obtained from hydrogenation and heat treatment to vegetable oils such as palm kernel
and arachis.
• Hydrogenation saturates unsaturated glycerides and heat treatment splits some of the
triglycerides into fatty acid and partial esters (mono and di glycerides).
• Most synthetic fat bases are made by first hydrolyzing the vegetable oil, then
hydrogenating the resulting fatty acids and finally esterifying the acids by heating with
glycerol.

Advantages
1. Their solidifying points are unaffected by overheating.
2. They have good resistance to oxidation because their unsaturated fatty acids have been
reduced.
3. The difference between melting and setting points is small; generally, only 1.5 to 2
o
C and seldom
over 3
o

C. Hence, they set quickly, the risk of sedimentation is low and they are easier to
administer.
4. The melting point depression caused by fat soluble drugs can be counteracted by choosing a
high melting point grade, while the hardness and brittleness that sometimes results from a high
content of insoluble powder can be prevented by using a low melting point grade.
5. High softening point grades are advantageous for tropical and sub-tropical formulations.
6. They usually contain a proportion of partial glycerides some of which e.g. glyceryl monostearate,
are w/o emulsifying agents and therefore their emulsifying and water absorbing capacities are
good.
7. No mould lubricant is needed because they contract significantly on cooling.
8. They produce suppositories that are white and almost odorless and have very attractive, clean
and polished appearance.

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Disadvantages
1. They should not be cooled in a refrigerator or ice because they become brittle if cooled quickly.
Additives such as polysorbate 80 correct this fault.
2. They are more fluid than Theobroma oil when melted and at this stage sedimentation is greater.
Thickeners such as magnesium stearate, bentonite reduce this problem.
3. The release and absorption of drugs in the body may differ for Theobroma oil and synthetic
bases.

PROPRIETARY SYNTHETIC BASES
Whitepsol (formerly called Imhausen)
o It consists of triglycerides of saturated vegetable acids (C
12
to C
18
) with varying
proportions of partial esters.
o The W45 grade is used for general dispensing.
Massa Estarinum
o It consists of mixture of tri, di and monoglycerides of saturated fatty acids with chain
lengths of C
11
to C
17
. Grade B is recommended for general dispensing.
Massuppol
o This differs from the previous materials in being single general purpose base with only
one modification, for cold moulding.
o It consists of glyceryl esters, mainly of lauric acid to which a small amount of glyceryl
monostearate has been added to improve its water absorbing capacity.
o The B.P.C allows the use of hydrogenated vegetable oils provided the melting point of
the suppositories is not above 37
o
C.

WATER SOLUBLE OR WATER MISCIBLE BASES
Glycero-Gelatin Base

 This is a mixture of glycerol and water into a stiff jelly by adding gelatin.
 It is used for making jellies, suppositories and pessaries and its proportion is changed
according to its intended purpose.
 Glycero-gelatin dissolves in body secretions and therefore is preferable to a fatty base for
administering antiseptics.
 Since, solution is slow, drug release is more prolonged than from fatty base.
 At present the B.P allows a maximum disintegration time of 1 hr. for Glycerol Suppositories
made with gelatin of B.P standard.
USP: Glycerin 70%, Gelatin 20% + water 10%
BP : Glycerin 70%, Gelatin 14% + water 16%

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Disadvantages of glycero-gelatin base :
Glycero-gelatin base suppositories are less often used than fatty base suppositories because-
1. They have a physiological action (used as laxative)
2. They are more difficult to prepare and handle. Lubrication of the mould is essential.
3. Their solution time depends on the content and quality and gelatin and the age of the base.
4. They are hygroscopic. So a careful storage is required. It also leads to dehydration of the rectal
mucosa with consequent irritation; this is an advantage where a laxative effect is required.
5. Gelatin is incompatible with protein precipitants such as tannic acid.


MACROGOLS (PEG)
Properties
 Long chain polymers of ethylene oxide with general formula HOCH
2
(CH
2
OCH
2
)
8
CH
2
OH
 Exist as liquid if their average molecular range from 200 to 600 and they exist as wax like solid
it is above 1000.
 Their water solubility, hygroscopicity and vapour pressure with increase in average molecular
weight.
 They do not hydrolyse or deteriorate and are physiologically inert and do not support mold
growth.
 The PEG suppositories can be prepared by both moulding and cold compression methods.
Advantages Of Macrogols
1. The mixtures have melting point above 42
o
C. Hence, cool storage is not required, they are
satisfactory for use in hot climates, and administration is easy because they are not slippery to
handle.
2. Because of this high melting point they do not melt in the body but gradually dissolve and
disperse, freeing their medication slowly and providing longer action than fatty bases.
3. Their physical properties can be varied by suitable admixture of high and low polymers. High
polymers give hard products that disintegrate and release their drug slowly.
4. They do not stick to the mould since they contract on cooling.
5. Because of their high molecular weight solution of high viscosity are produced when they
disperse in the body.
6. They absorb water well and have excellent solvent properties.
7. Products have clean smooth appearance.
Disadvantages Of Macrogols
1. They are hygroscopic so careful storage is required. Irritancy can be reduced by incorporating
about 20% of water in the mass or by instructing the patient to dip the preparation in water just
before insertion. This type of base is suitable for systemically active drugs.
2. Its good solvent properties can result in retention of the drug in the liquefied base in the body
with consequent reduction in therapeutic activity.
3. Products sometimes fracture on storage, particularly if they contain high solubility of macrogols
which can lead to a super saturated solution in the water and subsequent crystallization and this
the mass granular and brittle.

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4. Crystal growth of certain medicaments may occur particularly if they are partly in solution and
partly in suspension in the base. This makes the product brittle and crystals may be irritating
because they are large and takes longer time to dissolve.
5. They are incompatible with bismuth salts, tannins and phenol. They lower the activity of some
antibacterial agents and dissolve certain plastics necessitating care in choosing containers.
Selection Or Choice Of Suppository Base
There are several factors which are to be taken into consideration for choice of the suppository base,
but one of the main factors is the solubility of the drug in the vehicle or base. For effective release from
the base, a fat-soluble drug is best formulated in an aqueous base and a water-soluble drug in a fatty
base. Others factors are-
1. Composition of the base
2. Melting behavior of the base
3. Rheological properties of the base
4. Systemic absorption
5. Also the ideal properties (that mentioned before).

Que- ‘For effective release from the base a fat-soluble drug is best formulated in an aqueous base and a
water-soluble drug in a fatty base’ –explain the statement.
Depending on the characteristics of its vehicle a suppository will either dissolve in the rectal fluid or
melted on the mucous layer. Drugs that are highly soluble in the suppository base have not a tendency
to leave the vehicle but suspended drug particles have a tendency to leave the vehicle under the
influence of gravity or motility movements and then start dissolving in the rectal fluid. The drug
solubility in the rectal fluid determines the maximum attainable concentration for absorption. So when
a fat-soluble and water soluble drug is formulated in a fatty base and aqueous base respectively, the
drug is likely to be in solution to an appreciable extent or completely in the respective vehicle and
consequently the tendency of the drug to leave the vehicle will be small and thus the release rate into
the rectal fluid will be low. This is obviously unfavorable for rapid absorption. On the other hand, when
a fat-soluble and water soluble drug is formulated in a aqueous base and fatty base respectively, the
drug is likely to be in solution to small extent in the respective vehicle and consequently the tendency
of the drug to leave the vehicle will be increase and thus the release rate into the rectal fluid will be
high.

When the drugs solubility in fat and water are both low no definite rule can be given. It may well be
that the dissolution rate will become the controlling step and thus it seems advisable to use micronised
drug particles.

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General Summary Of Relationship Of Drug Release To The Drug And Suppository Base


RELEASE MECHANISMS FROM SUPPOSITORY
Insertion of a suppository into the rectum results in a chain of events leading to the absorption of the
drug. This is represented in a simplified scheme in following Figure. Depending on the character of its
vehicle, a suppository will either dissolve in the rectal fluid or melt on the mucous layer. Since the
volume of rectal fluid is so small, dissolution of the complete vehicle will be difficult and requires extra
water. Due to osmotic effects (of the dissolving vehicle) water is attracted, with a resultant unpleasant
sensation for the patient. Independent of the vehicle type, drugs dissolved in the suppository will diffuse
out towards the rectal membranes. Suspended drugs will first need to leave the vehicle (if it is water
immiscible) under the influence of either gravity or motility movements and then begin to dissolve in
the rectal fluid.
Dissolved drug molecules will have to diffuse through the mucous layer and then into and through the
epithelium forming the rectal wall. The process of absorption will be by passive diffusion, as it is
throughout the whole gastrointestinal tract for almost all drugs.
Active transport processes, as found in the upper regions of the gastrointestinal tract, have not been
shown to be present in the rectal area.

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OTHER ADDITIVES IN FORMULATION
Antioxidants
Preservatives
Emulsifiers (Wool fat, wool alcohol, polysorbates)
Hardening agents (Beeswax, Macrogol)
Viscosity modifiers (Mg stearate, Bentonite, Aerosil-200)

ANTIOXIDANTS
 It protects 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

EMULSIFYING AGENTS
 These are increase the water absorbing capacity of fatty bases.
Examples-
 Poly sorbates (TWEEN 60, 20, 80)
 Wool alcohol
 Wool fats

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.

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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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
 Magnesium stearate
 Stearyl alcohol
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
 Glycerin
 Glycol
 Tween 80
 Tween 85

PREPARATION OF
Suppositories And Pessaries

Three Methods
Moulding
Hand rolling
Compression

1. MOULDING
Preparation Of Suppositories in Moulds

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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.

Cleaning Of Moulds

Normal Capacities Of Moulds
 1g (15gr)
 2 g (30gr)
 4 g (60gr)
 8 g (120gr)

Ways Of Preparing Proprietary Suppositories – Conventional Moulds

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Plastic Moulds
Plastic Moulds –
polythene, polyvinyl chloride or a
complex film with polyvinyl
chloride.
Choice depends on stability of
contents to air and moisture.

Calibration Of Mould
Calibration of mould is necessary
before preparing suppositories and
pessaries.
The capacity of the mould varies with the different bases.
Each mould should be calibrated using the base alone, weighing the products and taking the mean
weight as true capacity.
 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.
Displacement Values
 The volume of the suppositories is uniform but the weight differs because there is difference in
densities of the medicaments and base.
 So the allowance must be made for the change in the density of the mass due to added
medicaments.
 The displacement value of a drug is the number of parts by weight of medicament that displaces
one part by weight of the base.
Displacement Values Of Some Medicaments
Name of the medicament Displacement value
Aminophylline 1.5
Zinc oxide 5.0
Resorcinol 1.0
Tannic acid 1.0
Bismuth subgallate 3.0
Hydrocortisone 1.5
Peru balsam 1.0

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Why A Knowledge Of Displacement Values Is Important For Pharmacists?
An understanding of the implications of displacement values is essential in ensuring that the correct
amount of drug is contained within a defined quantity of a dosage form.
Calculation Of Displacement Value
If the displacement value of a particular drug is not known it can be calculated by the following method:
1. Prepare six suppositories using the base alone. Let the weight of these be A mg
2. Prepare six suppositories containing a known percentage (40%) of a drug. Let the weight of
these be B mg
3. Calculate the amount of base present in the medicated suppositories. Let the weight be C mg
4. Calculate the amount of medicament present in the suppositories. Let the weight be D mg
5. Therefore, (A-C) will be the weight of the base displaced by the medicament.
6. Displacement value of the medicament for a particular base shall be:
Displacement value= D/(A-C)

Lubrication Of Mould
Must provide a buffer film
between the suppository and
the metal to easy removal of
suppositories from moulds.

2. HAND ROLLING
Hand moulding is useful
when we are preparing a
small number of
suppositories.

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3. COMPRESSION MOLDING
Large Scale Operation

1. Prepared mass C is placed in a cylinder A
2. It is forced through narrow opening D by means of piston B
into a mould.
3. Threads of mass pass in the mould G and are compressed until
a homogenous fused mass is formed in E.
4. On removal of retaining plate F the suppositories are ejected
by further pressure.
5. The mass and compression cylinder of the machine may be
chilled to prevent heat of compression from making the mass
too fluid.
6. Useful for moulding suppositories containing insoluble solids
(no risk of sedimentation) or thermolabile medicaments.
7. Unsuitable for glycero-gelatin products.

 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.

Procedure :
Advantages
1. It is a simple method
2. It gives suppositories that are more elegant than
hand moulded suppositories
3. In this method sedimentation of solids in the base is
prevented
4. Suitable for heat labile medicaments
Disadvantages
1. Air entrapment may take place
2. This air may cause weight variation
3. The drug and/or the base may be oxidized by this
air.

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PACKAGING AND LABELLING FOR SUPPOSITORIES


Labelling :
 Store in a cool place
 For rectal use only or not to be taken orally
 Moisten before use (for glycero-gelatin and macrogol bases)

PACKAGING AND LABELLING FOR PESSARIES


Labelling :
 Moisten the pessaries with water before insertion to reduce stinging caused by osmotic
withdrawal of water to reduce the tissues during solution in vagina.
 For vaginal use only or not to be taken orally.
 Store in a cool place.

QUALITY CONTROL OF SUPPOSITORIES
1. Test of Appearance (size, shape)
2. Uniformity of weight
3. Test of physical strength
4. Test of Disintegration
5. Test of Dissolution rate
6. Test of Melting range
7. Test of Softening time
8. 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.
 It occurs due to crystallization of bases.
 This also effect the melting and rate of absorption of drugs.

PACKAGING AND STORAGE
Polyethylene glycol suppositories stored at usual room temperature without the requirement of
refrigeration.
STORAGE CONDITION
 It is stored at 10-15
o
C
 Used air tight container
 The suppositories with cocoa butter stored at < 30
o
C
 The suppositories with glycero-gelatin stored at < 35
o
C

COMPOSITION Of A Suppository -
1. Active ingredient(s)
2. Suppository base
3. Diluent
4. Absorbent
5. Surfactant
6. Lubricant
7. Antimicrobial preservatives

SUPPOSITORIES AVAILABLE IN COMMERCIAL MARKET

Diclofenac Sodium Paracetamol 125 mg

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GYNOXIN= Metronidazol+ Neomycin Sulphate+ Nystatin+ Polmyxin B (Vag. Prep)
- Vaginal trichomoniasis, bacterial or fungal infection
ARIPROCT= Cinchocain HCL 0.5%+ Esculin 1%+ Hydrocortisone+ Neomycin Sulphate (Rectal. Prep)
- Pruritus ani, Haemorrhoids, Anal fissure, Proctitis
OFRAN= Ondansetron (Anti-emetic drug) – Prevention of nausea & vomiting.
TYCON= Tioconazole (Vag. Prep) – Vulval & vaginal candidiasis.
CLOFENAC= Rheumatoid arthritis, Osteoarthritis, Ankylosing spondylitis, Migraine, Muscle ache, Pain.
FAST= Paracetamol (Non-opioid Analgesic) – Fever and Mild to moderate pain.













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