Suppositories and Pserries

1. Suppositories & Pessaries
Lecture # 13
Pharmacy Practice-IIA (Dispensing Pharmacy) [PHM-3624]
Rahat Fatima (Lecturer DOP, IIUI)

2. Reference Book
Jannie Watson, Rees J, Smith I. Pharmaceutical
Practice. 5th Ed. Churchill Livingstone; 2014.
Chapter # 37 (Pg. 349-355)

3. INTRODUCTION
Drug administration by the rectum can be used for
local or systemic action. Dosage forms used include
suppositories, rectal tablets, capsules, ointments and
enemas. Vaginal administration can be for both local
and systemic action, using pessaries and vaginal
formulations of tablets, capsules, solutions, sprays,
creams, ointments and foams.

4. INTRODUCTION
Suppositories and pessaries are drug delivery
systems where the drug is incorporated into an inert
vehicle; base. Suppositories are formed by melting the
base, incorporating the drug and then allowing them to
set in a suitable metal or plastic mold.

5. SUPPOSITORY BASES
A number of criteria can be identified as desirable in an ideal
base, including:
● Melt at, or just below, body temperature or dissolve in body
fluids
● Solidify quickly after melting
● Easily molded and removed from the mold
● Chemically stable even when molten
● Release the active ingredient readily
● Easy to handle
● Bland, i.e. non-toxic and non-irritant.

6. SUPPOSITORY BASES
No base meets all these
requirements, so a
compromise is required.
There are two groups of
materials, the fatty bases
and the water-soluble or
water-miscible bases.

7. The Fatty Bases
Theobroma oil
Theobroma oil, a naturally occurring oil, has a melting
point range of 30–36°C and so readily melts in the
body. It liquefies easily on heating but sets rapidly
when cooled. It is also bland*, therefore no irritation
occurs. The main technical difficulty is the ease with
which lower melting point polymorphic forms of
Theobroma oil are formed.

8. The Fatty Bases
Theobroma oil
The stable β-form has a melting point of 34.5°C and forms
after melting at 36°C and slowly cooling. If it is overheated,
the unstable α-form (melting point 23°C) and γ-form
(melting point 19°C) are produced. These forms will
eventually return to the stable form but this may take
several days. The melting point is a problem in hot climates
and can be reduced further by the addition of a soluble
drug.

9. The Fatty Bases
Theobroma oil
The latter effect can be counteracted by adding
beeswax (up to 10%), but care must be taken not to
raise the melting point too high, as the suppository
would not melt in the rectum. In addition, Theobroma
oil is prone to oxidation. Theobroma oil shrinks only
slightly on cooling and therefore tends to stick to the
suppository mold; thus requiring a mold lubricant.

10. The Fatty Bases
Synthetic Fats
These are hydrogenated vegetable oils. Synthetic fatty
bases have many of the advantages but there are a
few potential problems:
● The viscosity of the melted fats is lower than that of
theobroma oil. As a result there is a greater risk of
drug particles sedimenting during preparation leading
to a lack of uniform drug distribution. This problem is
partly compensated for in that these bases set very
quickly

11. The Fatty Bases
Synthetic Fats
These bases become brittle* if cooled too rapidly, so
should not be refrigerated during preparation
These bases are produced in series of grades, each
with different hardness and melting point ranges.
These can be used to compensate for melting point
reduction by soluble drugs. However, release and
absorption of the drug in the body may vary depending
on the base being used.

12. Water-Soluble and Water Miscible Bases

13. Glycerol-gelatin Bases
These bases are a mixture of glycerol and water
stiffened with gelatin. The commonest is Glycerol
Suppositories Base BP, which has 14% weight in
weight (w/w) gelatin, and 70% w/w glycerol. In hot
climates, the gelatin content can be increased to 18%
w/w. Pharmaceutical grade gelatin is a pathogen-free,
purified protein produced by the hydrolysis of the
collagenous tissue, such as skins and bones, of
animals. Some people may have ethical problems with
the use of such a product.

14. Glycerol-gelatin Bases
Two types of gelatin are used for pharmaceutical
purposes: Type A, which is prepared by acid hydrolysis
and is cationic, and Type B, which is prepared by
alkaline hydrolysis and is anionic. Type A is compatible
with substances such as boric acid and lactic acid,
while Type B is compatible with substances like
ichthammol and zinc oxide. The ‘jelly strength’ or
‘bloom strength’ of gelatin is important, particularly
when it is used in the preparation of suppositories or
pessaries.

15. Glycerol-gelatin Bases
Glycerol-gelatin bases have a physiological effect
which can cause rectal irritation because of the small
amount of liquid present. As they dissolve in the
mucous secretions of the rectum, osmosis occurs
producing a laxative effect. The solution time depends
on the content, quality of the gelatin and the age of the
suppository. Because of the water content, microbial
contamination is more likely than with the fatty bases.
Preservatives may be added to the product, but can
lead to problems of incompatibility. In addition, glycol-
gelatin bases are hygroscopic and therefore require

16. Macrogols
These polyethylene glycols can be blended together to
produce suppository bases with varying melting points,
dissolution rates and physical characteristics. Drug
release depends on the base dissolving rather than
melting (the melting point is often around 50°C).
Higher proportions of high molecular weight polymers
produce preparations which release the drug slowly
and are also brittle.

17. Macrogols
Less brittle products which release the drug more
readily can be prepared by mixing high polymers with
medium and low polymers. Details of combinations
which are used are found in the Pharmaceutical
Codex (1994). Macrogols have several properties
which make them useful as suppository bases
including the absence of a physiological effect, are not
prone to microbial contamination and have a high
water-absorbing capacity. As they dissolve, a viscous
solution is produced which means there is less
likelihood of leakage from the body.

18. Disadvantages of Macrogols
The macrogol bases have a number of disadvantages.
They are hygroscopic, which means they must be
carefully stored, and this could lead to irritation of the
rectal mucosa. This latter disadvantage can be
alleviated by dipping the suppository in water prior to
insertion. They become brittle if cooled too quickly and
also may become brittle on storage. Incompatibility
with several drugs and packaging materials, e.g.
benzocaine and plastic, may limit their use. In addition,
crystal growth occurs, with some drugs causing
irritation to the rectal mucosa and may prolong
dissolution times.

19. Preparation of
Suppositories

20. Preparation of Suppositories
Suppositories are made using a metal or plastic
suppository mould. Traditional metal moulds are in two
halves which are clamped together with a screw. The
internal surface is normally plated to ensure that the
suppositories have a smooth surface. Before use the
mould should be completely cleaned by washing carefully
in warm, soapy water and thoroughly dried, taking care
not to scratch the internal surface. The exact shape can
vary slightly from one mould to another.

21. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
The bases used, most commonly, for extemporaneous
preparation of suppositories and pessaries are the
synthetic fats and glycerol-gelatin base.
1. When calculating the quantity of ingredients it is
necessary to prepare excess due to unavoidable wastage.
Usually, an excess of two should be calculated for, e.g. to
prepare 12 suppositories, calculate for 14.

22. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
2. The mould should be carefully washed and dried.
3. Ensure that the two halves fit together correctly. This is
necessary to ensure that there is no leakage of material.
They usually have code letters and/or numbers which
should match.
4. For some bases the mould will need to be lubricated.

24. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
5. If a lubricant is necessary, apply it carefully to the two
halves of the mould using gauze or other non-fibrous
material. Do not use cotton wool as fibres may be left on the
mould surface and become incorporated into the
suppositories.
6. Invert the mould to allow any excess lubricant to drain off.
7. Accurately weigh the required amount of base. If large
lumps are present the material should be grated.

25. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
8. Place in a porcelain basin and warm gently using a water
bath or hot plate. Allow approximately two-thirds of the base
to melt and remove from the heat. The residual heat will be
sufficient to melt the rest of the base.
9. Reduce the particle size of the active ingredient, if
necessary. Either grinding in a mortar and pestle or sieving

26. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
10. Weigh the correct amount of medicament and place on
a glass tile (ointment slab).
11. Add about half of the molten base to the powdered
drug and rub together with a spatula.
12. Scrape the dispersion off the tile using the spatula and
place it back in the basin.

27. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
13. If necessary, put the basin back over the water bath to
remelt the ingredients.
14. Remove from the heat and stir constantly until almost
on the point of setting. If the mixture is not stirred at this
stage the active ingredient will sediment and uniform
distribution of the drug will not be achieved.

28. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
15. Quickly pour into the mould, slightly overfilling each
cavity to allow for contraction on cooling. Do not start
pouring the suppositories while the mixture is still very
molten. If this is done, a suspended drug will sediment to
the bottom of the mould and the base shrinks excessively
so that the tops become concave.

29. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
16. Leave the mould and its contents to cool for about 5
min and then, using a spatula, trim the tops of the
suppositories. Do not leave the suppositories too long
before trimming, as they will be too hard and trimming
becomes very difficult.
17. Allow cooling for another 10–15 min until the
suppositories are completely firm and set. Do not try to
speed up the cooling process by putting the mould in a
refrigerator. Synthetic fats in particular are inclined to

30. Preparation of suppositories
containing an active ingredient which
is insoluble in the base
18. Unscrew the mould and remove the suppositories.
19. Each perfect suppository should then be wrapped
in greaseproof paper and packed in an appropriate
container and labelled.

31. Preparation of suppositories containing
an active ingredient which is insoluble in
the base
When preparing suppositories where the active
ingredient is either a semi-solid, is soluble in the base
or is a liquid which is miscible with the base, the
melting point of the base will be lowered. In these
situations, a base with a higher than normal melting
point should be used if available. The base is melted
as normal and the active ingredient is added directly to
the base and incorporated by stirring.

32. Preparation of suppositories containing
an active ingredient which is insoluble in
the base
Moulds are made in four sizes: 1 g, 2 g, 4 g and 8 g.
Unless otherwise stated, the 1 g size is used for
suppositories. The same moulds are used to prepare
pessaries, when the two larger sizes are generally used. A
suppository mould is filled by volume, but the suppository
is formulated by weight. The capacity of a suppository
mould is nominal and each mould will have minor
variations. Therefore, the weight of material contained in
different moulds may be different and will also depend on
the base being used. It is therefore essential that each
mould be calibrated for each different base.

33. Mould Calibration
The capacity of the mould is confirmed by filling the
mould with the chosen base. The total weight of the
perfect suppositories is taken and a mean weight
calculated. This value is the calibration value of the
mould for that particular base

34. Displacement values
The volume of a suppository from a particular mould is
uniform but its weight can vary when a drug is present
because the density of the drug may be different from that
of the base. For example, a drug which has twice the
density of the base will occupy half the volume which the
same weight of base occupies, and a drug whose density
is four times that of the base will occupy a quarter the
volume which the same weight of base occupies.
Allowance must be made for this by using displacement
values (DV).

35. Displacement values
The displacement value of a drug is the number of parts
by weight of drug which displaces 1 part by weight of the
base. Displacement values for a variety of medicaments
are given in Table 37.2. Other reference sources such as
the Pharmaceutical Handbook (Wade 1980) and the
Pharmaceutical Codex also give information on
displacement values. Minor variations may occur in the
values quoted so it is always advisable to indicate the
source of your information

37. Displacement values
Displacement values in the literature normally refer to
values for Theobroma oil. These values can also be used
for other fatty bases. With glycerolgelatin suppository
base, approximately 1.2 g occupies the same volume as 1
g of Theobroma oil. Using this information, the relevant
displacement values can be calculated.
There may be occasions when information on the DV of a
drug is not available. In these situations the DV must be
determined

38. Calculation of quantities when the
active ingredient is stated as a
percentage
A displacement value is not required when calculating
quantities stated as percentages.
When there is more than one active ingredient present the
quantity of each medicament is calculated and the amount
of base is calculated using the displacement value for
each ingredient

39. Containers for Suppositories
Glass or plastic screw-topped jars are the best choice
of container for extemporaneously prepared
suppositories and pessaries. Cardboard cartons may
be used but these offer little protection from moisture
or heat for hygroscopic materials.

40. Shelf-Life
Suppositories and pessaries are relatively stable
preparations, if well packaged and stored at a low
temperature. Unless other information is available, an
expiry date of 1 month is appropriate.

41. Labelling for Suppositories
Adequate information should appear on the label so
that the patient knows how to use the product. In
addition, the following information should appear:
‘Store in a cool place’ and ‘For rectal use only’ or ‘For
vaginal use only’, whichever is appropriate.

42. Patient Advice
In addition to what appears on the label, patients
should be told to unwrap the suppository or pessary
(this may appear to be unnecessary advice but there
is sufficient evidence to show that it is not always
done) and insert it as high as possible into the rectum
or vagina. It may be helpful to provide the patient with
a diagram and instruction leaflet, such as that
produced by the National Pharmaceutical Association.
When suppositories are for children it is likely that an
adult will have to carry out the insertion.