SUPPOSITORIES

& PESSARIES
PROF THIRU GOVENDER

PHARMACEUTICAL SCIENCES,
UKZN
Suppositories
Definition: solid, uniformly medicated, conical or
torpedo-shaped dosage form for rectal
administration. They melt slightly below body
temperature so that after insertion the mass melts
and the medicament is liberated into contact with
the rectal mucosa.
Applications - Used for 3 reasons:
1. To exert a local effect on the rectal mucosa
2. To promote evacuation of the bowel
3. To provide systemic effect
 Advantages
§ Can be administered to very ill or unconscious
patients.
§ Can be administered to patients who are
nauseous or vomiting.
§ Several categories of patients may use the
rectal route more easily than the oral route
e.g. very young / old, mentally impaired.
§ Can be used to administer drugs which are
sensitive to gastric juices.
§ Drugs that cause GIT side-effects may be
administered rectally.
§ Unpleasant taste and smell becomes
insignificant when administered rectally.
§ Can be used to administer drugs destroyed
by the 1st pass effect.
§ Drugs that are candidates for abuse e.g
suicide may be formulated as suppositories.
Disadvantages
§ Slow and sometimes incomplete absorption
has been reported, as well as considerable
inter and intra-subject variation in absorption
rates.
§ Discomfort to the patient may be experienced.
§ Leakage of suppository may occur.
§ Problems with large scale manufacture may
occur.
Absorption of Drug from the Rectum
 1. Location of the Suppository
in the Rectum
ž Venous drainage → 3 separate veins:
— Lower and middle haemorrhoidal veins drain
directly into the general circulation via the inferior
vena cava.
— Upper superior rectal vein drains into the portal
vein which flows to the liver.
ž Therefore 50-70% of all rectal dosage forms are
first to carried into the systemic circulation
before reaching the liver.
Venous drainage of the
human rectum
2. Quantity of Fluid Available
ž Fluid volume available for drug dissolution is
very small (approx. 3mL spread in a layer of
approx. 100µm thick over the organ).
ž Volume enlarged only under non-physiological
circumstances e.g. osmotic attraction by water
soluble vehicles or diarrhea.
3. Properties of Rectal Mucosa
ž Effect of composition, viscosity, surface
tension of rectal fluids unknown.
ž Estimated from data available for other
parts of the gi tract.
 4. Contents of the Rectum
ž Rectum usually empty except temporarily when
faecal matter arrives from higher parts of colon.
ž Material is either expelled or transported back
into the colon, depending on the voluntary
control exhibited on the sphincter of the anus.
ž Rectal wall exerts pressure on the suppository -
abdominal organs may simply press on to
rectum especially when body is in upright
condition - may stimulate spreading and thus
promote absorption.
5. Motility of the Rectal Wall
ž Second source of pressure is motility of
muscle of the rectal wall - originates from the
normally occurring colonic motor complexes.

ž These are waves of contractions running over

the wall of the colon and are associated with
the presence of food residues in the colon.
 Properties of an Ideal
Suppository Base
• Melting range lower than approx. 37°C
• Non-toxic, non-irritating, non-sensitizing
• Compatible with a wide variety of drugs and promotes
optimal drug release
• Must not have metastable intermediates
• Must shrink on cooling → easily removed from mould
• Must have wetting and emulsifying properties
• Chemically and physically stable during storage
• Possess a high water number
• Easily moulded or manufactured
• Economical
Classification of Suppository Bases
1. Fatty bases
a) Theobroma oil
b) Synthetic Hard Fat
2. Water-soluble and water miscible Bases
a) Glycero-gelatin
b) Macrogols
3. Miscellaneous
4. Xerogels
1. Fatty Bases
ž designed to melt at body temperature
a) Theobroma Oil
• Yellowish – white solid with an odour of
chocolate.
• Mixture of glycerol esters of stearic, palmitic,
oleic and other fatty acids.
Advantages:
1. Melting pt. 30-36°C
2. Readily melted on warming, rapid setting on
cooling.
3. Miscible with many ingredients.
4. Bland and non-irritating.
Disadvantages:
1. Polymorphism
2. Adherence to the mould
3. Softening point too low for hot climates
4. Melting point ↓ by soluble ingredients
5. Rancidity on storage
6. Poor water-absorbing ability
7. Leakage
8. Expense
b) Synthetic Hard Fat
• Prepared by hydrolyzing the vegetable oil, then
hydrogenating the resulting fatty acid and then
re-esterifying the acids by heating with glycerol.

Advantages of Synthetic hard fats over

Theobroma oil:
1. Their solidifying points are unaffected by
overheating.
2. Display good resistance to oxidation because
their unsaturated fatty acids have been
reduced.
3. Difference between melting and setting points is
small (±1.5 - 2°C), therefore set quickly → ↓ risk
of sedimentation and easier to administer.
4. Series of grades with different melting point
ranges and degrees of hardness are available.
5. Good water – absorbing capacity.
6. No mould lubrication required → contract
significantly on cooling.
Disadvantages:
1. Low viscosity → allows for sedimentation.
2. Brittle if cooled rapidly therefore avoid
refrigeration during preparation.
 2. Water-soluble &
Water Miscible Bases
a) Glycero-gelatin
• mixture of glycerol and H2O gelled by the
addition of gelatin.
• Glycerol suppository mass usually contains
70% glycerol and a minimum of 14% gelatin.
• High concentrations of gelatin are required
for hot countries.
Disadvantages:
1. Physiological effects → laxative action.
2. Unpredictable solution time → inter-batch
variation.
3. Hygroscopic → requires protection from heat
and moisture and has dehydrating effect on
mucosa.
4. Microbial contamination is likely to occur.
5. Long preparation time and requires lubrication.
b) Macrogols
• Consists of mixtures of polyethylene glycols
of different molecular weight.
• Melting point well over body temp.- mixes with
rectal fluid.
• Because of high melting point - suited for
application in tropical climates.
Advantages:
1. No laxative effect.
2. Microbial contamination less likely.
3. Contracts on cooling → no lubricant required.
4. Produces high viscosity solutions.
5. Good solvent properties.
6. Gives products with smooth, clean appearance.
Disadvantages:
1. Hygroscopic – irritates mucosa - painful
sensation for patient.
2. Poor availability of medicament → good solvent
properties → retention of drug.
3. Incompatible with some drugs e.g. Benzocaine
( bismuth salts- ↓ activity of QAC’s & parabens).
4. Brittleness.
5. Crystal growth of certain drugs may occur.
3. Miscellaneous Bases
ž Mixtures of oleaginous & water-soluble
bases.
ž Melt at body temp. & form an emulsion with
rectal fluids e.g. Tween 60.
ž Suppositories using soap as a base are also
included.
 4. Xerogels
ž Solutions of active in methylcellulose or PEG.
ž Can be used in body orifices with a small
amount of body fluids.
 The Drug

Solubility
§ Drug solubility indicates type of drug i.e.
solution suppository or suspension suppository.
§ Drug solubility in rectal fluid determines the
maximum attainable concentration and thus
driving force for absorption.
§ If drug has a high vehicle water partition
coefficient – will be in solution greatly in the
vehicle – therefore tendency to leave vehicle
will be small – thus release rate - low and
hence unfavourable for rapid absorption.
§ Lipid solubility required for drug penetration
through rectal membranes – hence balance to
be achieved.
Surface Properties
§ Important as particles will be transferred from one
phase to another.
§ Happens when drug is brought into contact with
the vehicle and air has been displaced from its
surface. If not achieved agglomerates may form.
Adversely affects final content uniformity.
§ If wetting by vehicle has taken place displacement
by rectal fluid will be required to let the drug go
into solution- is prerequisite for absorption. This is
reason why surfactants may be added.
Particle Size
§ Important technologically & biopharmaceutically.
Particle size should be limited to prevent undue
sedimentation during or after preparation.
§ Smaller the particle size - the less the possible
mechanical irritation to the patient and higher the
dissolution rate.
Amount of Drug
§ If number of particles increases, will increase
rate to form agglomerates and also affects
viscosity of the molten base.
 Other Additives
1. Antioxidants → if base/medicaments is
susceptible to oxidation.
2. Preservatives → for water soluble and water-
miscible bases.
3. Emulsifiers → may be used to facilitate the
incorporation of aqueous solutions or polar
liquids.
4. Hardening agents → may be required to ↓
sedimentation rate.
 Specific Problems in
Formulating Suppositories
1. Water → combination of H2O & natural oils
or fats → following problems:
i. ↑ oxidation of fat → include antioxidant.
ii. H2O evaporates → substances crystallizes out.
iii. Incompatibilities accelerated.
iv. Good growth medium for micro-organisms →
include preservative.
2. Hygroscopicity of Common Bases
• Glycerol- gelatin bases → lose moisture in dry
climates and absorb H2O in humid climates.
• Macrogols absorb moisture in humid climates

3. Incompatibilities
• Macrogols incompatible with many substances

4. Viscosity
• Important w.r.t manufacturing & bioavailabilty
• Melted cocoa butter → low viscosity
• Glycerol- gelatin and PEG type bases → high
viscosity
5. Brittleness
• Theobrama oil suppositories → elastic, do
not fracture easily.
• Macrogols and synthetic fat with high degree
of hydrogenation and high steratae content
→ brittle.
• To overcome brittleness:
a. The temperature of the melted base and the
mould should be as similar as possible.
b. Addition of small amounts of Tween 80/85 castor
oil, glycerin or propylene glycol.
6. Density
• Important when the amount of drug per
suppository must be calculated → volume of
mould is fixed → therefore mass of individual
suppository depends on the density of the
base.
• If volume contraction occurs during cooling
compensation must be made.
7. Volume Contraction
• Good mould release
• Contraction hole formation
8. Lubricants
• Bases with a low volume of contraction require
lubricants.
• Theobroma oil → alcoholic solutions of
glycerin, propylene glycol and silicones used.
• Glycero-gelatin → liquid paraffin and arachis oil
used.
9. Rancidity & Antioxidants
• Fats which oxidize become rancid.
• Resistance to oxidation based n amount of
peroxide.
• Can add antioxidants e.g.: tocopherol, phenol,
ascorbic acid, a-naphthol
10. Surface Changes
• Efflorescence (flowering) → small crystals
develop in the form of a powder film on the
surface of the suppository.
• Caused by substance having a melting point
close to room temperature.

• To overcome this problem:

i. Store at the recommended temperature
ii. Replace raw materials of low melting with
substances having higher melting points
iii. Use close-fitting packaging e.g. blister packs
 Hard Moulding
ž Base and medicament are cold rolled into a
cylindrical rod → lengths containing the correct
doses are cut off and one end is pointed →
used for small quantities only.
ž Labour intensive method.
 Compression Moulding
ž Blend mass is cold grated and then extruded into
a mould → requires special suppository
compression machine.
Advantages:
ž No heating/melting therefore no sedimentation or
polymorphic changes → produce elegant
suppositories → perfect shape.
ž Suitable for heat labile drugs.
Disadvantages:
ž Difficult to exclude air → slow process.
ž Cannot use disposable moulds.
Pour Moulding
• Most common method
• Re-usable and disposable moulds can be used
• Involves the following general steps:-
• Melting the base
• Incorporating any medicament
• Pouring melt into mould
• Allowing melt to cool and set into suppository
• Removing suppository from the mould
Suitable for large scale manufacture
→ ± 3500 suppositories per hour can be
produced on a rotary table
- Disposable moulds are used most frequently
- Advantage for disposable moulds:
i. Most suitable for hot climates
ii. Do not require cleaning after use
iii. Provide protection from atmosphere
 Reusable
Metal Moulds

Disposable Plastic Moulds

Used also as Packaging
 Evaluation of Suppositories
1) Appearance → includes odour, colour, surface
condition and shape → BP and USP.
2) Weight → BP test – uniformity of weight . Weigh
individually 20 suppositories, taken at random
and determine the average weight. Not more
than 2 of the individual weights deviate from the
average weight by more than 5% and none
deviates by more than 10%.
3) Disintegration → BP requires that all
suppositories comply with the test for
disintegration of suppositories
4) Melting behaviour → also known as the
liquefaction time test → measure liquefaction
time of suppositories in an apparatus that
stimulates in vivo conditions.
5) Mechanical strength → designed to measure
brittleness of the suppository. Active can affect
strength of the base therefore test is important
to avoid formulation problems.
6) Content of active ingredient → BP requires all
suppositories to pass uniformity of content test.
7) Drug release – in vitro or in vivo
In vitro release rate → 3 methods:
i. Place suppository in specific volume of water
at 37°C and measure amount of drug released
after set intervals.
ii. Diffusion of active from moulten suppository
into agar gel plate.
iii. Diffusion of active through a semi-permeable
membrane from the moulten suppository base
into an aq. buffered medium.
In vivo determination of release:
i. Blood and urine samples.
ii. Measuring pharmacological effect after dosing.
iii. Active remaining in the rectum after specific
time intervals is determined.
Release process of a drug from a
suspension suppository
 Pessaries
ž Pessaries are solid medicated preparations
designed for insertion into the vagina, usually to
exert a local effect.
ž Mainly for local effect e.g. treatment of
Trichomonas and candida infections.
ž Can be used for systemic effect → oestrogens
and prostaglandin analogues → also
progesterone.
ž Usually buffered at pH 4.5.
ž Usually prepared in a 4-8g mould.
ž Glycerol-gelatin bases used → well tolerated
and relatively soluble in vaginal secretions.
PEG promotes irritation and fatty recipients
may result in leakage.