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Mr. Pankaj Kusum Ramdas Khuspe
M. Pharm (Pharmaceutics)
Introduction, definition, advantages and
disadvantages, desirable features of suppositories,
factors affecting rectal absorption.
Suppository bases specifications and desired‐
features, classification and selection of suppository
bases, special bases.
Formulation and specific problems involved in
formulating suppositories, large scale manufacture
with equipments involved in each step, packaging.
Quality control tests, Examples of official
solid dosage forms
intended for insertion in to body
cavities or orifices (Rectum,
Vagina & Urethra)
where they melt or dissolved &
exert localized or systemic effect.”
“Suppositories are solid dosage forms intended
for insertion in to body cavities or orifices
(Rectum, Vagina & Urethra) where they melt
or dissolved & exert localized or systemic
o It avoid first pass effect.
o Melt at body temperature.
o It gives localized and systemic action.
o It can be given to unconscious patient.
o It is easy to use for pediatric and geriatric
o Useful to produce local effect.
o Useful for rapid and direct effect in rectum.
o Useful to promote evacuation of bowel
o Convenient for those drug causes GIT irritation ,
o Unit dosage form of the drug.
o Irritant drug cant administered
o Embarrassment to patients
o Need to store at low temp.
o Cant easily prepared
o Defecation may interrupt the absorption process.
o absorbing surface area of the rectum is much
smaller than that of the small intestine.
o fluid content of the rectum is much less than that of
the small intestine; this may effect dissolution rate,
o Some drug may be degraded by the microbial flora
present in the rectum.
o Drug with narrow therapeutic margin,can not be
interchange without the risk of toxicity.
Should be completely non-toxic & non-irritant.
Should be compatible with a broad variety of drugs.
Should be non-sensitizing.
Should have wetting & emulsifying properties.
Should be stable on the storage i.e. does not
change color, odor or drug release pattern.
Should have acid value below 0.2.
Should have iodine value less than 7.
Should have “saponification value" ranges from 200
Factor affecting rectal (drug) absorption
1. Physiologic Factor
a. Colonic Content
c. pH and lack of buffering capacity of the rectal fluid
2. Physiochemical characteristics of the drug
a. Lipid water solubility of a drug (partition coefficient)
b. Degree of ionization
c. Concentration of a drug in a base
3. Physiochemical Characteristics of the Base
a. Nature of the Base
b. Presence of Adjuvant in Base
Factor affecting rectal (drug) absorption
1) Physiologic Factor:
The human rectum is approximately 15-20 cm in the
length, when empty of fecal material;
It contains 2-3 ml of inert mucous fluid.
In resting state, the rectum is non motile.
There is no villa or microvillus on rectal mucosa.
Physiological factors include:
1. Colonic Content
3. pH and lack of buffering capacity of the rectal fluid
When systemic effect are desired from
suppository greater absorption may be
expected from a rectum that is void than that
with fecal matter.
An evacuation enema maybe
administered before insertion of a
Diarrhea, colonic obstruction and tissue
dehydration influence the rate & degree of
drug absorption from rectum.
A) Colonic Content:
Drugs absorbed rectally partially by pass portal
circulation, thereby enabling drug destroyed in liver to
exert systemic effect.
Depending on the height at which absorption occurs at
rectum, the drug passes into inferior, middle or
superior hemorrhoid veins.
The inferior is nearest to the anus, the upper
hemorrhoid vein —> portal circulation, thus it is
advisable to keep suppositories in the lower part of
50% -70% of drug administered rectally, reported to go
directly into general circulation.
C) pH and lack of buffering capacity of the
rectal fluid :
Rectal fluids are neutral (pH 7-8), have no
effective buffer capacity.
The barrier separating colon lumen from the
blood is preferentially permeable to the
unionized forms of drugs, thus absorption of
drug would be enhanced by change in pH of the
rectal mucosa to one that increase the
proportion of unionized drugs.
2) Physiochemical characteristics of the drug
A) Lipid water solubility of a drug (partition
- The lipid water partition coefficient of a drug is important
in selecting the suppository base and in anticipating drug
release from that base
- Lipophilic drug, in other word, distributed in a fatty
suppository base has fewer tendencies to escape to the
- Thus water-soluble salt are preferred in fatty base
suppository. water-soluble base e.g: PEG, which
dissolve in the rectal fluids, release both water-soluble
and oil-soluble drugs.
B) Degree of ionization:
The barrier separating colon lumen from the
blood is preferentially permeable to the
unionized forms of drugs, thus absorption of
drug would be enhanced by increase the
proportion of unionized drugs
C) Concentration of a drug in a base:
- The more drugs in a base, the more drug will be
available for absorption.
- If the concentration of the drug in the intestinal lumen is
above a particular amount, the rate of absorption is not
change by further increase in concentration of drug.
- In general, the rate limiting step in drug absorption from
suppository is the partitioning of the dissolved drug from
the melted base and not the rate of solution of drug in
the body fluid.
- Scientists showed that: the rate, at which the drug
diffuses to the surface of the suppository, Particle size,
and presence of surface-active agents are factors that
affect drug release from suppositories.
3) Physiochemical Characteristics
of the Base and Adjuvant:
1) Nature of the Base:
- Suppository base capable of melting,
softening or dissolving to release the drug for
- If the base irritating the colon, it will promote
colonic response, lead to increase bowl
movement and decrease absorption.
2) Presence of Adjuvant in Base :
Adjuvant in a formula may affect drug
absorption, change the rheological properties
of the base at body temperature, or affected
the dissolution of the drug.
Consider the following points
1. Medication intended for local or systemic use.
2. Site of application-rectal, vaginal and urethral.
3. Desired effect- quick, slow or prolonged.
First preliminary evaluation.
Stability at 4o
C and at room temp.
Following parameter are studied:
Drug availability. Etc.
Formulation of Suppositories
a. Suppositories base
d. Anti oxidants.
f. Penetration enhancers
Ideal Properties of Bases
It must retain the shape and size.
It should melt at body temperature.
It should be non-irritant.
It should shrink sufficiently to remove from mould.
It should not interfere in release or absorption of
It should permit incorporation of drug.
It should be compatible with variety of drugs.
It should be physically stable on storage.
It should not be soften or harden on storage.
1 Origin & Chemical Composition:
A brief description of the composition of the
base reveals the sours of the origin (natural
or synthetic or modified natural products).
Physical or chemical in- compatibilities with
other constituents may be predicted if the
exact formula composition is known including
preservatives, antioxidants and emulsifiers
2 Melting Range:
Suppository bases don't have a sharp melting
point, their melting characteristics are expressed
as ranges, indicating the temperature at which
the fats start to melt and the temperature at
which completely melted.
Melting range is usually determination by " Wiley
melting point", "Capillary melting point".
3 Solid-Fat Index (SFI):
One can determine the solidification and melting
ranges of fatty bases as well as the molding
character, surface feel and hardness of the bases.
A base with sharp drop in solids over a short
temperature span proves brittle if molded too quickly.
The solid content at room temperature could
determine suppository hardness. Since skin
temperature is about 32° C, one can predict that
would be dry to touch from a solid content over 30%
at that temperature.
4- Solidification Point:
This test allow to determine the time required for
solidifying the base, when it is chilled in the mold.
if the interval between the melting point and
solidifying point is 10° C or more, time required
for solidification may have to be shortened for
amore efficient manufacturing procedure by
E.g.: If melting point 33° C and solidifying point
20° C then it will be liquid for 13° C, then the drug
will sediment and the apex of the suppository will
contain all the drug.
5- Hydroxyl Value:
"It is the number of milligrams.of KOH (Potassium
hydroxide) that would neutralize the acetic acid used to
acetylate 1g of fat.”
It reflects the mono- and di-glyceride content of a fatty
6- Saponification Value:
“The number of milligrams of KOH (Potassium hydroxide)
required to neutralize the free fatty acids and saponify
the ester contained in 1 g of a fat.”
From saponification value we can know the type of
glyceride present (mono-, di- or tri-) and also amount
7- Iodine Value:
It is the number of grams of Iodine that reacts with l00 g
of fat or other unsaturated material.
The possibility of decomposition by moisture, acids,
oxygen (which leads to rancidity of fats) increases with
higher iodine value.
8- Water Number:
It is the amount of water in grams that can be
incorporated in l00g of fat.
The "water number" can be increased by the addition of
surface- active agents.
9- Acid Value:
It is the number of milligrams of KOH (Potassium
hydroxide) required neutralizing the free fatty acids in I g
Low acid value or absence of acid value is important for
good suppository bases.
• Cocoa butter is fat obtained from the roasted seed of
• At room temperature it is a yellowish, white solid
having a faint, agreeable chocolate like odour.
• Chemically, it is a triglyceride (combination of glycerin
and one or different fatty acids) primarily of
oleopalmitostearin and oleodistearine.
• It melts at 30 - 350
Melting just below the body temperature.
Maintaining its solidity at usual room temperatures.
Readily liquefy on heating and solidify on cooling.
Exhibits marked polymorphism.
Stick to mould.
Leakage from body cavity.
Immiscibility with body fluid.
Chloral hydrate or lactic acid liquefy it.
It is a mixture of glycerin and water which is made
stiff by the addition of gelatin.
It is colourless, transparent, translucent in nature.
It is soft to touch.
It melts at 30 - 350
Type of gelatin bases: to avoid incompatibility.
Type A or Pharmagel A: acidic in nature and used for
Type B or Pharmagel B: alkaline in nature and used for
Used for vaginal suppositories.
Glycero- Gelatin Base
It melt at body temperature.
It mix with body fluid.
It can be used to prepare suppositories using boric acid,
chloral hydrate bromides, iodides, iodoform opium etc.
Difficult to prepare and handle.
Chance of bacterial growth.
Hygroscopic in nature. (become hard on drying and soft in
cont with moisture)
Laxative in action.
Incompatible with tannic acid, gallic acid, ferric chloride etc.
Polyethylene Glycols/ Macrogols:
Water-miscible bases are composed of PEGs possessing a molecular weight greater
than 1000 g/mol.
The melting point of these higher grades of PEGs increases as the molecular weight
increases, e.g. the melting points of PEG 1000 and PEG 8000 are 370
C and 600
Typically the melting point of PEG suppository bases is 420
C; this is generally
achieved and controlled using the appropriate mixtures of grade of this polymer.
The higher melting point of these systems obviates the need for storage under cold
In addition to controlling the melting point, different molecular weights of this polymer
may also be blended to control the mechanical properties of PEG based
In this scenario, the lower-molecular-weight PEGs, e.g. PEG 400, will act to reduce
the brittle behaviour of these suppository bases.
PEG is known to enhance the solubility of therapeutic agents and therefore this
interaction between the drug and polymer may affect the subsequent release of the
drug from the liquefied base.
Secondly, the solubility of the drug in the solid base may change as functions of both
storage conditions and time and this may result in crystal growth within the
These are commonly known as carbowax.
These are available in solid, liquid or semi-solid
state depending on molecular weight.
1. They are chemically stable.
2. Inert, Non-irritant.
3. Do not allow bacterial growth.
4. Physical properties changes according to molecular
5. Provide prolonged action.
6. Do not stick to mould.
7. Suppositories are clean and smooth in appearance.
Hygroscopic in nature.
Incompatibility with some drugs tannins phenol
Good solvent properties.
Supersaturation takes place.
Advantage of Emulsifying bases
They solidify rapidly.
They are non-irritant.
The lubrication of mould is not required.
Overheating does not affect the physical properties
of the base.
They can absorb fairly large amount of water or
The white, odourless, clean and attractive
suppositories are produced.
They are less liable to get rancid.
Disadvantage of Emulsifying bases
They should not be cooled rapidly in a
refrigerator because they become brittle.
They are not very viscous on melting, so the
medicaments incorporated with the base
settle down rapidly.
They consist of triglycerides of saturated
vegetable fatty acid with varying percentage
of partial esters.
A small amount of beeswax is added for use
in hot climate.
It should not be cooled rapidly as it become
brittle and fracture.
Lubrication is required.
It is a mixture of mono, di and triglycerides of
saturated fatty acids having the formula
C11H23COOH to C17H35COOH.
This is also known as adeps solidus.
It is a white, brittle, almost odourless and
It has a m.p. 33.5 to 35.50
They are available in various grades but
grade B is commonly used in dispensing.
It consists of glyceryl esters mainly of lauric
acid to which small amount of glyceryl
monostearate has been added to improve its
water absorbing capacity.
It is the oldest and simplest
method of suppository
preparation and may be
used when only a few
suppositories are to be
prepared in a cocoa butter
It has the advantage of
avoiding the necessity of
heating the cocoa butter.
A plastic-like mass is
prepared by triturating
grated cocoa butter and
active ingredients in a
The mass is formed into a ball in the palm of the
hands, then rolled into a uniform cylinder with a
large spatula or small flat board on a pill tile.
The cylinder is then cut into the appropriate number
of pieces which are rolled on one end to produce a
Effective hand rolling requires considerable practice
and skill. The suppository "pipe" or cylinder tends to
crack or hollow in the center, especially when the
mass is insufficiently kneaded and softened.
1. Melting the suppository base
2. Dispersing or dissolving the drug in the melted
3. The mixture is removed from the heat and poured
into a suppository mold.
4. Allowing the melt to congeal
5. Removing the formed suppositories from the mold.
The fusion method can be used with all types of
suppositories and must be used with most of them.
Small scale molds are
capable of producing 6
or 12 suppositories in a
produce hundreds of
suppositories from a
Compression molding is a method of
preparing suppositories from a mixed
mass of grated suppository base and
medicaments which is forced into a
special compression mold using
suppository making machines.
The suppository base and the other
ingredients are combined by thorough
The friction of the process causing the
base to soften into a past-like
On a small scale, a mortar and pestle may be used
(preheated mortar facilitate softening of the base).
On large scale, mechanically operated kneading
mixers and a warmed mixing vessel may be applied.
In the compression machine, the suppository mass
is placed into a cylinder which is then closed.
Pressure is applied from one end to release the
mass from the other end into the suppository mold
When the die is filled with the mass, a
movable end plate at the back of the die is
removed and when additional pressure is
applied to the mass in the cylinder, the
formed suppositories are ejected.
The end plate is returned, and the process is
repeated until all of the suppository mass has
The method requires that the capacity of the
molds first be determined by compressing a
small amount of the base into the dies and
weighing the finished suppositories.
When active ingredients are added, it is
necessary to omit a portion of the suppository
base, based on the density factors of the
Packaging and storage
Suppositories are usually packed in tin or aluminum,
paper or plastic.
Poorly packed suppositories may give rise to
staining, breakage or deformation by melting.
Both cocoa butter and glycerinated gelatin
suppositories stored preferably in a refrigerator.
Polyethylene glycol suppositories stored at usual
room temperature without the requirement of
Quality Control of Suppository
1) Surface appearance and shape:
To evaluate: absence of fissuring –
absence of migration of active ingredient,
absence of pitting, absence of fat blooming
(dullness of surface)
2) MELTING RANGE TEST:
Macro-melting range: measures the time it takes for the
entire suppository to melt when immersed in a constant
temperature (370C) water bath.
Micro-melting range: is the melting range measured in
capillary tubes for the fat base only.
The apparatus used for measuring the melting range of
the entire suppository is a USP tablet disintegration
The suppository is completely immersed in the constant
temperature water bath, and the time for the entire
suppository to melt or dispense in the surrounding water
The in-vitro drug release pattern is measured by using
the same melting range apparatus.
3) LIQUIFACTION OR SOFTENING TIME
TESTS OF RECTAL SUPPOSITORIES:
The "softening test" measures the liquefaction
time of rectal suppositories are an apparatus
in-vitro conditions (at 37oC).
4) BREAKING TEST:
It is designed as a method for measuring the
fragility or brittleness of suppositories.
The apparatus consists of double-wall chamber
in which the test suppository is placed.
Water at 37C is pumped through the double
walls of the chamber, and the suppository,
contained in the drug inner chamber, supports a
disk to which a rod is attached.
The outer end of the rod consists of another disc
to which weights are applied.
5) Mechanical strength:
It is a force necessary to break a supp. And
indicate whether supp is brittle or elastic. ( not
less than 1.8-2 Kg) by Erweka method
6) Melting & solidification
Solidification can be determine by using
evacuated flask into which the melt is placed,
the temp of cooling is noted to determine the
7) DISSOLUTION TESTING:
The patterned is measured by using the
same melting range apparatus.
If the volume of water surrounding the
suppository is known, then by measuring
aliquots of the water for drug content at
various intervals within the melting period.
A (time versus drug release) curve could be
established and can be plotted.
Suppository should be protected from heat,
preferably stored in the refrigerator.
Glycerinated gelatin suppositories should be
protected from heat, moisture, and dry air by
packaging in well-sealed containers and
storing in a cool place.