SUPPOSITORIES

Excipients in suppositories
The list of possible excipients is more limited for suppositories than for
other dosage form types.

Examples include:
1.surface-active agents;
2.agents to reduce hygroscopicity
3.agents to control the m.p. of the base.
1. Surface-active agents
• WHY?
• to enhance the wetting properties of the suppository base with
the rectal fluid.
• This will enhance drug release/dissolution.

• Used mainly for formulations composed of a lipophilic suppository

base and/or a lipophilic drug.

• Examples: Spans and tweens

2. Agents to reduce hygroscopicity
• e.g. colloidal silicon dioxide
• WHY?
to reduce the uptake of water from atmosphere during storage
which may:
❖Enhance physical and chemical stability of the dosage
form/therapeutic agent.
❖result in changes to the mechanical properties (softening) and
shape of these dosage forms.
moisture-resistant packaging is needed.
3. Agents to control the m.p. of the base
• m .p of the base may be manipulated WHY?:
❖storage at higher temperature
❖presence of a therapeutic agent that is soluble in the suppository base.

• to increase the m. p of suppositories prepared using fatty bases we

may include:
❖beeswax
❖stearic acid
❖ colloidal silicon dioxide
❖magnesium stearate
• To reduce m. p of the fatty suppository base :
to enable melting within the rectum, we can use glyceryl
monostearate, polysorbate 80 & propylene glycol.

• the melting point of PEG-based suppositories may be controlled by:

altering the grade of PEG used.
- higher-molecular-weight PEG: increase m p
- low-molecular-weight PEG ( 400): decrease m p
 MANUFACTURE OF SUPPOSITORIES
Suppositories are manufactured principally using a moulding method
1. a method in which the base is heated to above the melting
temperature,
2. the drug is dispersed (or dissolved) in the heated liquid
3. the molten product is poured into suppository moulds
4. This is then allowed to cool (usually in a refrigerator) prior to
removal and packaging.
Lubrication of Moulds
 Suppositories prepared using cocoa butter or glycerol-
gelatin bases may stick in the metallic suppository
mould after cooling.
• To prevent this, the moulds are usually lubricated.
• Composition of lubricant must differ from base to prevent any
interaction.
❖arachis oil for glycerol-gelatin suppositories
❖alcohol/surfactant mix ( soap) for cocoa butter supp.

Plastic moulds do not

require lubrication.
In large scale manufacture
the molten formulation may be injected directly into the final
packaging (termed mould strips), which are then sealed.
RECTAL Formulations
other than
SUPPOSITORIES
For local effect
• fatty ointments are used in ttt of haemorrhoids,.
• large-volume enemas are used in ttt of rectocolitis. WHY?
This enables the drug to reach the upper part of the rectum
and the sigmoid colon.

For systemic effect

 tablets, capsules, microenemas & liquid suppositories are used.
 Tablets
• are not very attractive as they can’t disintegrate rapidly. WHY?
• owing to small amount of water present in rectum.

Capsules
➢Are mostly of soft-shell type used to achieve a systemic effect
➢ are usually filled with a solution or suspension of the drug in vegetable
oil or paraffin.
Microenemas
• are solutions or dispersions of the drug in a small
volume ( 3 ml) of water or vegetable oil.
• This form is supplied in a small plastic container
equipped with an application tube.
• After insertion of the tube, the container is emptied by
compressing the bulb.
• The advantage of this delivery system is:
no melting and dissolution process is necessary before
drug release can start, if water is used as a vehicle.
Microenemas are still of limited applicability WHY?
• because of its relatively high cost compared to suppositories,
• administration can’t be performed easily by patients themselves,
and it is rather difficult to deliver the total content of the plastic
container.
Liquid Suppositories
• exist as liquid in vitro but gel in vivo,
• by modulating the gelation temperatures of certain polymer (e.g.
poloxamer) solutions.
• The polymer composition is adjusted as such that the polymer
solution gels at temperatures just below body temperature.
• Mucoadhesive polymers could be also included so that the liquid
suppositories not only gel at 30–36°C, but also remain in the rectum
without leakage after administration.
 Problems in Suppository Formulations
1- Water in suppositories
2- Hygroscopicity
3- Drug-excipient interactions
4- Viscosity
5- Brittleness
6- Density
7- Lubrication of moulds
8- Volume contraction
9- Displacement value:
10- Rancidity
1- Water in suppositories
Water is not preferred for dissolving drugs in suppositories for the
following reasons:
a. Water causes oxidation of fats.
b. If supp are manufactured at a high T, water evaporates, drugs may
crystallize out.
c. Drug excipient interactions are more likely to happen in the presence
of water.
d. Bacterial contamination may be a problem, so we may be forced to
add a preservative.
2- Hygroscopicity
Glycerogelatin suppositories
• absorb moisture in humid conditions.
Polyethylene glycol bases
• Hygroscopicity depends on chain length of molecule.
• It increases with increased molecular weight.
3- Drug-excipient interactions
Incompatibilities exist between:
• PEG and some drugs, e.g.
• salicylic acid (soften the PEG base)
• penicillin G (decomposes in PEG bases)

4- Viscosity
 When the base has low viscosity, sedimentation of the drug is a
problem.
 2% aluminium monostearate may be added to increase the viscosity
of the base and decrease sedimentation of the drug.
 Cetyl and stearyl alcohols or stearic acid are added to improve the
consistency of suppositories.
5- Brittleness
• Cocoa butter suppositories are elastic, not brittle, while synthetic
fat bases are brittle.

• This problem can be overcome by:

keeping the temperature difference between the melted base and
the mould as small as possible.

• Materials that impart plasticity to a fat and make them less

brittle are:
small amounts of tween 80, castor oil, glycerin or propylene
glycol.
6- Density
Density of the base is one of the factors that 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.
8- Volume contraction
On solidification: volume of suppository decreases.
Adv: This contraction helps the suppository to easily slip
away from the mould, preventing the need for a
lubricating agent.
Disadv: a hole forms at the open end.
• an inelegant appearance to the suppository.
• weight variation
This contraction can be minimized by:
➢ pouring the suppository mass slightly above its congealing
temperature into a mould warmed to about the same temperature.

➢ overfill the molds, and scrape off the excess mass which contains
the contraction hole.
9- Displacement value
• Defined as amount of drug that displaces one part by weight of
the base.
? g Drug will displace 1 g base
DV = density of drug/density of base
• 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,
• hence the density of the medicament will affect the amount of
the base required for each suppository
10- Rancidity
• Unsaturated fatty acids in the 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.
VAGINAL DOSAGE
FORMS
local effect for the treatment of:
• infection (fungal and bacterial)
• hormone deficiency (topical hormone replacement therapy for the
treatment of vaginal atrophy).

systemic drug absorption (not popular)

• steroid hormones (e.g. oestradiol acetate) for the treatment of the
systemic symptoms of the menopause and for long-term
contraception
• prostaglandins (for cervical ripening)

• ensure correct placement and retention in vagina

• may require the use of special applicators
Vaginal physiology
• There are ridges (folds) in the vagina,
(vaginal rugae),
• ↑ surface area and hence drug
absorption from vagina.
• The vaginal rugae will enhance the
retention of the dosage form in the
vagina, thereby facilitating prolonged
drug release.
• Limited volume of fluid within the vagina
will limit the dissolution of moderate to highly lipophilic drugs.

• The vagina is highly vascular a plexus of arteries and veins is

located round the vagina.

• No first-pass metabolism Venous blood supply from the vagina

does not enter the portal system.

This renders the vagina a useful site for the systemic

administration of therapeutic agent.
 Types of Vaginal Dosage Forms
• pessaries (vaginal suppositories)
• semisolid formulations
• tablets
• capsules
• vaginal implants.
(1) Vaginal suppositories (Pessaries)
• Vaginal suppositories, also called pessaries, are usually globular,
oviform, or cone-shaped and weigh about 5 g when cocoa butter is
the base.

 Pessaries are formulated using glycerol-gelatin or

PEG bases, into which the drug is incorporated.
 The pH of pessaries that contain an aqueous phase
may be buffered to pH 4.5.
(2) Semisolid formulations
• Semisolid formulations (creams, ointments & gels)

• foams - aerosol products based on o/w creams

• Many vaginal products are buffered to an acid pH about 4.5, consistent
with the normal vagina.
• This acidity discourages pathogenic organisms and provides a favorable
environment for eventual recolonization by the acid- producing bacilli
normally found in the vagina (Lactobacilli help to keep the vagina healthy
by producing lactic acid, hydrogen peroxide, and other substances that
inhibit the growth of yeast and other unwanted organisms).
(3) Tablets and capsules
• Vaginal tablets and capsules are used for delivery of:
• antimicrobial agents
• steroid hormones.
• Disintegrants may be incorporated into tablets WHY?
due to relatively low content of aqueous fluid in the vagina under
normal physiological conditions.
 When vaginal inserts are prescribed, the pharmacist should instruct the
woman to dip the tablet into water quickly before insertion.
 The administration of tablets and capsules to the vagina requires the use
of an applicator.
(4) Vaginal implants
• Vaginal implants are solid formulations that provide a controlled
release (decrease frequency) of therapeutic agent into the vaginal
fluids and may be used to achieve either a local effect or systemic
absorption.

 E.g. Femring, a doughnut-shaped implant

provides controlled systemic absorption of
oestradiol.

The mechanical properties of the product

ensure excellent retention
 URETHRAL SUPPOSITORIES
• Urethral suppositories, also called bougies, are slender, pencil-
shaped suppositories intended for insertion into the male or female
urethra.
When cocoa butter is employed as base:
male supp: 4 g, ~ 140 mm long.
female supp: 2 g, ~ 70 mm long.
Urethral suppositories may be antibacterial or a local anesthetic
preparative for a urethral examination.
 QUALITY CONTROL TESTING OF SUPPOSITORIES

1. Weight Variation Test

2. Melting range test

3. Liquefaction Time
4. Breaking Test
5. Dissolution Test
6. Stability Test
 1. Weight Variation Test

According to the USP weight variation test is run by:

• weighing 20 suppositories individually
• calculating the average weight (weight of 20 supp./20)
• comparing the individual suppository weights to the average.

As per USP the suppositories complies with the test if:

• not more than 2 supp. deviate from average wt by more than 5 %
• none deviates by more than 10%.
2. Melting range test

The test determines:

the time taken by an entire suppository to melt when it is immersed in a
constant temperature bath at 37°C.

The experiment could be done by

using the USP Tablet Disintegration
Apparatus.
3. Liquefaction Time or Softening Time Test

• In this test a U tube is partially immersed in a constant temperature bath

(35-37°C).
• There is a constriction in the tube in which the suppository is kept
• above the suppository, a glass rod is kept.
• The time taken for the glass rod to go through the suppository and reach the
constriction is known as the liquefaction time or softening time.
4. Breaking Test (Hardness)
The breaking test is designed as a method for measuring the fragility or brittleness
of suppository. .
• The suppository is placed in the instrument; 600 g is
added and left for one minute.
• If not broken, add 200 g every one minute until the
suppository is broken.
• The hardness of the suppository is calculated by
adding the weights together.
• But if the suppository is broken before the end of the
last min. the last weight is canceled.
5. Dissolution Test
• By using different types of apparatus such as:
• wire mesh basket
• or dialysis tubing
6. Stability testing
• Cocoa butter suppositories on storage “bloom”; i.e., they form a white powdery
deposit on the surface.
• This can be avoided by: storing the suppositories at uniform cool temperatures and
by wrapping them in foils.

• Fat based suppositories harden on storage, i.e., there is an upward shift in melting
range due to slow crystallization to the more stable polymorphic forms of the base.
• The softening time test can be used for stability testing
• If we store the suppositories at an elevated temperature, just below its melting
range, immediately after manufacture, the aging process is speeded up.