For Diploma In Pharmacy

1. Suppositories and Pessaries
PRADEEP PATIL

2. Definition
A suppository is a medicated solid dosage form
generally intended for use in the rectum, vagina and
to a lesser extent, the urethra.
After insertion they melt or soften at body
temperature, whereas vaginal suppositories called as
pessaries, are also made as compressed tablets that
disintegrate in body fluids.

3. Advantages
Oral route not
useful.
Patient – GIT
problems,
Nauseous or
post
operative.
Very young ,
very old, or
the mentally
disturbed.
Slowly
absorbed &
sustained
action.
Drug - not
stable at GI
pH or
susceptible to
enzymatic
attack in the
GI tract
Drug - first
pass
metabolism.
Drugs with
an
unacceptable
taste can be
administered.
Produce local
effect.

4. Disadvantages
Mucosal
irritation
Traditional
Issues-
feeling of
aversion
Leakage
Sometimes
incomplete
absorption.
Stored in
refridgerat
or (10-20
centigrade)
Irritant
drugs can
not
administer
ed.
Large scale
production
difficult
and costly
Shelf life
(stringent
storage
conditions)
.
GI state
affects
absorption

5. Types of suppositories
• Cone shaped, weighing 1 – 2 g
Rectal
• Globular, oviform, cone or wedge shaped, weighing 2 – 8 g
• Made from glycero-gelatin or macrogol base
Vaginal (pessaries)
• Thin pencil shaped pointed at one end
• Male bougies – 4 g and 100-150 mm
• Female bougies – 2 g and 60 – 75 mm
Urethral bougies
• Thin pencil shaped with pointed ends
• 1.2 g and 9 – 10 mm long
Nasal bougies
• Pencil shaped
Ear cones

6. Size of suppositories
0 For Children
1,2 & 3 For rectal use
4 Pessaries
A & B Nasal &
urethral
bougies

7. Shape of suppositories

8. 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
Properties of an ideal suppository base

9. Types of suppositories bases
Suppository
bases
Fatty bases
Cocoa Butter/
Th.oil
Emulcified Th. oil
Hydrogeneted
oil
Water soluble or
water miscible
bases
Glycero-gelatin
Macrogols(PEG)

10. Fatty Bases

11. Cocoa Butter (Theobroma oil):
Properties It is the most widely used suppository base. And it
is used in the prescriptions when no base is
specified.
It is naturally occuring triglyceride with oleo palmito
stearin and oleo di stearin glyceride chain and contains
40% of the unsaturated fatty acid.
It is yellowish white, solid, brittle fat, which smells
and tastes like chocolate.
Its melting point lies between 30-35oC (86-95oF) its
iodine value is between 34 and 38 and its acid
value is no higher than 4.
It satisfies the requirements for an ideal base:non-reactive,
and melts at body temp.

12. Disadvantages
Polymorphism
Adherence to
mould
Low softening
point
Melting point
reduction
Deterioration
during storage
Poor water
absorbing
capacity
Leakage from
the body

13. 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.

14. Cocoa butter exits in four crystalline state
α form
• melts at 24oC
• Obtained by
suddenly
cooling
melted cocoa
butter to 0oC.
ß form
• Crystallizes
out of the
liquefied
cocoa butter
with stirring
at 18 to 23oC.
• Its melting
point lies
between 28
and 31oC.
ß` form
• changes
slowly into
the stable ß
form.
• Melts between
34 and 35oC.
• Change is
accompanied
by volume
contraction.
γ form
• melts at 18oC
• Obtained by
pouring cocoa
butter, before
it solidifies,
into a
container
which is
cooled at deep
freeze temp.

15. Cocoa
butter
<= 36°C
> 36°C
Stable ß crystals
with normal
melting point
Unstable γ crystals
melt about 15°C
Slow
Cooling
Rapid
Cooling
Heated
Unstable α crystals
melts about 20°C
Unstable forms return to stable form
after several days & may not set at
room temp. Or if set by cooling may
remelt in warm conditions

16. 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.

17. 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

18. Emulsifying bases / 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 oil.
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 hydrolysing the vegetable
oil, then hydrogenating the resulting fatty acids and finally esterifying
the acids by heating with glycerol.

19. Advantages Their solidifying points are unaffected by over heating.
They have good resistance to oxidation because their
unsaturated fatty acids have been reduced.
The difference between melting and setting points is small;
generally only 1.5 to 2oC. Hence, they set quickly, the risk
of sedimentation is low and they are easier to administer.
No mould lubricant is needed because they contract
significantly on cooling.
They produce suppositories that are white and almost
odourless and have very attractive, clean and polished
appearance.

20. Disadvantages 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.
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.
The release and absorption of drugs in the
body may differ for theobroma oil and
synthetic bases.

21. Synthetic bases
Whitepsol
• It consists of
triglycerides of
saturated vegetable
acids (C12 to C18)
with varying
proportions of partial
esters.
• The W45 grade is
used for general
dispensing.
Massa Estarinum
• It consists of mixture
of tri, di and
monoglycerides of
saturated fatty acids
• Grade B is
recommended for
general dispensing.
Massuppol
• 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.
• The B.P.C allows the
use of hydrogenated
vegetable oils
provided the melting
point of the
suppositories is not
above 37oC.

22. Water soluble or water
miscible bases

23. Glycero-gelatin
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 B.P made with gelatin of B.P standard.

24. Disadvantages
of glycero-
gelatin base
They have a physiological action (used as
laxative)
They are more difficult to prepare and handle.
Their solution time depends on the content and
quality of gelatin and the age of the base.
They are hygroscopic. So a careful storage is
required. It also leads to dehydration of the
rectal mucosa with consequent irritation.
Gelatin is incompatible with protein
precipitants such as tannic acid.

25. Macrogols (PEG)
Properties long chain polymers of ethylene oxide with general
formula HOCH2(CH2OCH2)8CH2OH
Exist as liquid if their average molecular weight 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.

26. Advantages of macrogols
1.The mixtures have melting point above 42oC. 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.

27. Advantages of macrogols
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.

28. 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.
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 , High solubility of
macrogols which can lead to a super saturated solution in the
water and subsequent crystallization produces brittleness.

29. Disadvantages of macrogols
4. Crystal growth of medicaments may occur if
they are partly in solution and partly in
suspension form. 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.

30. PREPARATION OF
SUPPOSITORIES
AND PESSARIES

31. Methods:
1.Moulding/ Hot process/ fusion
Method.
2.Hand rolling Method
3.Cold Compression Method.

32. Preparation of suppositories - Moulding/ Hot process/
fusion Method.

33. Cleaning of Moulds
Mould
Interior –
Don’t scrap
or rub with
abrasive
Immerse in
hot
detergent
water
Wipe with
soft cloth
Rinse
thoroughly

34. Normal capacities of Moulds
1g
(15gr)
2 g
(30gr)
4 g
(60gr)
8 g
(120gr)

35. Plastic Moulds
Heat sealable
laminated foil
Press on plastic caps
Plastic Moulds – polythene, polyvinyl chloride or a complex film
with polyvinyl chloride.
Choice depends on stability of contents to air and moisture.

36. 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.

37. 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.
• Number of parts by weight of medicament that displaces
one part by weight of the base.

38. 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

39. Lubrication of mould – must provide a buffer film
between the suppository and the metal
Synthetic fat or
macrogol base
Contract
significantly on
cooling
Lubrication is not
needed
Glycero-gelatin
base
Sticky nature
Oily lubricant –
liquid paraffin or
arachis oil
Theobroma oil
Oily lubricant
cannot be used
Soft soap -10 g
Glycerol – 10 ml
Alcohol(90%) – 50
ml

40.  Industry – silicone fluid is used as lubricant.
 Incompatibility between lubricant, medicament and adjuncts should be
checked.
 Lubricant should be applied on pad of gauze or muslin or with a small
fairly stiff brush.
 Cotton wool is unsuitable because fibers detach too easily.
 Avoid excess lubricant – drops on the sides and in the bottoms of the
cavities cause depression in the product.
 After lubrication mould is closed and inverted on a clean white tile to
drain.

41. General Methods of
preparation

42. Fatty base – suppositories containing insoluble solids –
theobroma oil and synthetic bases
1. Check the displacement values
of medicaments
2. Calculate the quantity of
medicaments
3. Excess quantity is weighed –
unavoidable wastage
Major loss due to sticking of the
material to the sides of the dish
So the smallest dish should be
selected.

43. 4. Initially weigh the quantity for
4 extra suppositories
After experience weigh the
quantity for 2 extra suppositories
5. Weigh the required amount of
fat in a porcelain dish
Avoid metal dishes due to
overheating problem

44. 6. Finely powder the medicaments and
pass it through sieve no. 180 and weigh
the required quantities
7. Heat a tile on water bath and mix the
powder on a tile with a flexible spatula
8. Place the base on water bath until 2/3rd
contents are melted and then remove it.
Overheating may occur if the base is
allowed to melt completely.
9. Rest of the base is melted with
continuous stirring with spatula and avoid
glass rod for stirring

45. 10. Pour about half of the base on to
the mixed medicaments
11. Prepare a smooth dispersion as
quickly as possible by levigating with
spatula
12. To prevent excessive cooling use
small tile and this will also avoid loss on
the edge of the tile
13. If the base is solidified hold the tile
on water bath for few seconds
14. Transfer the dispersion to the dish
and stir to form homogenous mixture

46. 15. Continue stirring until the mixture
begins to thicken
16. Then fill each cavity of the mould to
overflowing
Cavities are overfilled to prevent
depressions in the tops of the suppositories
due to the contraction of the base during
cooling
If there is delay to pour the mass into
cavities then continue the stirring because
setting of the mass will take place before
filling
This also prevents the sedimentation of
insoluble solids

47. 17. There may be solidification of mass
during pouring so reheat the mass and
make it pourable
The base of the dish should be wiped to
prevent contamination of mass with
water
18. Leave in a cool place until the mass is
set and remove the excess with a sharp
knife or razor blade or warm spatula
19. Put the knife or blade or spatula at an
angle of about 30°C and draw it from left
to right pressing down at the same time
20. Open the mould and remove the
suppositories. If difficult to open tap the
mould and remove it.

48. Additional precautions for theobroma oil suppositories
Thoroughly lubricate the mould and cool and drain
the excess in refrigerator or ice box
Cooling hasten setting of base and reduces
sedimentation of suspended solids
Take care not to over heat the base
If the base is too thick to pour then cool the base to
excess and again reheat it and then pour the base in
mould.

49. Hand rolling:
• Hand molding is useful when we are preparing
a small number of suppositories
The drug is
made into fine
powder
Incorporated
into suppository
base
By trituration or
kneading
Mass is rolled
into rod shape
by fingers
Rods are cut
into pieces
Desired shape is
given by hand

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

51. • 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

52. Packaging and labelling for suppositories
Rigid paperboard boxes Flat box with a lid
Labelling :
1. Store in a cool place
2. For rectal use only or not to be taken orally
3. Moisten before use (for glycero-gelatin and
macrogol bases)

53. Packaging and labelling for pessaries
Glass bottles Plastic bottles
Labelling :
1. Moisten the pessaries with water before insertion.
2. For vaginal use only or not to be taken orally.
3. Store in a cool place.