Suppositories and pessaries

SUPPOSITORIES AND
PESSARIES
Presented by
Nabina
1

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 sometimes called as
pessaries, are also made as compressed tablets that
disintegrate in body fluids.
2

BP DEFINITION : SUPPOSITORY
 “Suppositories are solid, single-dose preparations. The shape,
volume and consistency of suppositories are suitable for rectal
administration.”
3

BP DEFINITION: PESSARIES
“ Pessaries are single dose preparations. They have various shape
usually ovoid with a volume and consistency suitable or insertion
into vagina. They contain one or more active substances dispersed
or dissolved in suitable basses that may be soluble or dispersible or
melt at body temperature. Excipients such as diluents, adsorbents,
surface active agents, lubricants, antimicrobial preservatives and
colorizing material authorized by the competent authority may be
added if necessary.”
4

PESSAARIES
Common ingredients for inclusion in pessaries for local action
include:
 antiseptics
 contraceptive agents
 local anaesthetics
 various therapeutic agents to treat trichomonal, bacterial and
monilial infections.
5

Advantages
Oral route
not useful.
Patient – GIT
problems,
Nauseous or
post
operative.
Very young ,
very old, or
the mentally
disturbed.
Drug have GI
side effects.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.
Drug that
may be
abused as in
suicide.
6

Disadvantages
Mucosal
irritation
Traditional
Issues-
feeling of
aversion
Leakage
Sometimes
incomplete
absorption.
Inter and
intra
subject
variation.
Proctitis.
Large scale
production
difficult
and costly
Shelf life
(stringent
storage
conditions)
.
GI state
affects
absorption
7

DOSAGE FORM CHARACTERISTICS:
a. Rectal suppositories for adults weigh 2 g and are torpedo shape .
Children's suppositories weigh about 1 gm.
b. Vaginal suppositories or Pessaries weigh about 3-5gm and are
molded in globular or oviform shape or compressed on a tablet
press into conical shape.
c. Urethral suppositories called Bougies are pencil shape. Those
intended for males weigh 4 g each and are 100-150 mm long. Those
for females are 2 g each and 60-75 mm in length.
8

d. Nasal suppositories: Called nasal bougies or buginaria meant
for introduction in to nasal cavity.
•They are prepared with glycerogelatin base.
•They weigh about 1 g and length 9-10 cm.
e. Ear cones:
• Aurinaria and meant for introduction into ear.
• Rarely used.
• Theobroma oil is used as base.
• Prepared in urethral bougies mould and cut according to size.
9

THERAPEUTIC USES
 Suppository can be used for local or systemic effect.
 The action depends on nature of drug , concentration and rate of
absorption
 Rectal suppository are intended for treatment of constipation and
hemorrhoids.
 Suppositories are also administered for systemic action
(analgesics, antispasmodics, sedatives & tranquilizers).
12

FACTOR AFFECTING DRUG ABSORPTION FORM
RECTAL SUPPOSITORY:
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:
14

A) Colonic Content:
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 suppository.
Diarrhea, colonic obstruction and tissue dehydration influence
the rate & degree of drug absorption from rectum.
15

B) Circulation:
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 rectum. 50% -70% of drug administered rectally,
reported to go directly into general circulation.
16

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.
17

2.PHYSIOCHEMICAL CHARACTERISTICS OF THE
DRUG:
A)Lipid water solubility of a drug (partition coefficient
 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 surrounding queues
fluids.
 Thus water-soluble salt are preferred in fatty base
suppository. water-soluble base : PEG, which dissolve in the
rectal fluids, release both water-soluble and oil-soluble drugs.
18

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
19

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.
20

 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.
21

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 absorption.
 If the base irritating the colon, it will promote colonic response,
lead to increase bowl movement and decrease absorption.
22

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.
23

SPECIFICATIONS FOR SUPPOSITORY BASES :
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 incompatibilities
with other constituents may be predicted if the exact
formula composition is known including preservatives,
antioxidants and emulsifiers.
24

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", Incipient melting (or
thaw)point /Softening point.
25

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.
26

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 a more efficient manufacturing
procedure by refrigeration.
27

5- Hydroxyl Value:
It is the number of milligrams of KOH that would
neutralize the acetic acid used to acetylate 1g of fat. It
reflects the mono- and di-glyceride content of a fatty
base.
6- Saponification Value:
The number of milligrams of KOH 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 present.
28

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.
29

9- Acid Value:
It is the number of milligrams of KOH required
neutralizing the free fatty acids in 1g substance (fat). Low
acid value or absence of acid value is important for good
suppository bases.
30

A) Bases
B) Antioxidants
C) Emulsifying agents
D) Hardening agents
E) Preservatives
F) Thickening agents
G) Plasticizer
31
FORMULATION OF
SUPPOSITORIES

A) PROPERTIES OF AN IDEAL
SUPPOSITORY BASE:
The ideal suppository base may be described as follows :
 Melts at rectal temperature 36°C, or dissolve in rectal
fluid.
 Completely non toxic, and non irritating to sensitive and
inflamed tissues.
 Compatible with a broad variety of drugs.
 No metastable forms.
 Shrinks sufficiently on cooling to be released form the
mold without the need for mold lubricants.
 Non- sensitizing
32

 Has a melting and emulsifying property.
 Water number is high (a high percentage of water can
incorporated in it)
 It is stable on storage, dose not change odor, color,
release pattern.
 Can be manufactured by molding either by hand,
compression, machine .
 Acid value is below 0.2, saponification value ranges
from 200 to 245, and Iodine value is less than 7.
 SFI(solid fat index) curve is sharp, in other word, the
interval between melting point and solidification point is
small
33

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
34

TYPE OF SUPPOSITORY BASES:
A- Fatty Bases
B- Hydrophilic Suppository Bases
C-Water dispersible Bases
35

A. FATTY BASES:
Cocoa Butter (Theobroma oil)
It is the most widely used suppository base. It satisfies many
requirement for ideal suppository base.
1) Bland.
2) Non reactive.
3) Melt at body temperature.
 Cocoa Butter is a triglyceride, yellowish white, solid, brittle fat,
smells and taste like chocolate.
 Its melting point between 30-35° C, its’ iodine value is “between”
34-38 .
 Its acid value is no higher than 4, because cocoa butter can melt
and become rancid. So it must be stored in cool dry place
protected from light. 36

ADVANTAGES
 Melting range 30-36 0c,easily melts in the body
 Readily melted on warming,rapid settling on cooling.
 Miscible with many other ingredients.
 Non-irritating.
37

Disadvantages
Polymorphism
Adherence to
mould
Low
softening
point
Melting point
reduction
Deterioration
during
storage
Poor water
absorbing
capacity
Leakage
from the
body
38

POLYMORPHISM
( the property of existing in different crystalline forms).
 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.
39

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 a cool
cocoa butter,
before it
solidifies, into
a container
which is cooled
at deep freeze
temp.
40

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
41

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.
42

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
43

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.
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.
44

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 and seldom over 3oC. Hence, they
set quickly, the risk of sedimentation is low and they are
easier to administer.
The melting point depression caused by fat soluble drugs can
be counteracted by choosing a high melting point grade, while
the hardness and brittleness that sometimes results from a
high content of insoluble powder can be prevented by using a
low melting point grade.
45

Advantages High softening point grades are advantageous for
tropical and sub tropical formulations.
They usually contain a proportion of partial glycerides
some of which e.g. glyceryl monostearate, are w/o
emulsifying agents and therefore their emulsifying and
water absorbing capacities are good.
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. 46

Disadvant
ages
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.
47

B. HYDROPHILIC SUPPOSITORY BASES:
1-Glycerine Suppositories(USP):
Glycerine 91 g
Sod. Stearate 4g
Purified water 5g
To make approximately l00g
2- Glycerated gelatin suppositories(USP):
Drug & purified water 10g
Gelatin 20g
Glycerin 70g
-
48

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.
49

PREPARATION OF GLYCERO-GELATINE
BASES
GLYCEROL WATER GELATINE
GLYCERO-GELATINE BASES
50

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 and 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; this is an
advantage where a laxative effect is required.
51

MACROGOLS (PEG)
Properties long chain polymers of ethylene oxide with general formula
HOCH2(CH2OCH2)8CH2OH
Exist as liquid if their average molecular 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. 52

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.
• Softer, less brittle preparations that disperse and liberate their drug more
quickly are obtained by mixing high with either medium or medium and low
polymers or by adding plasticizers.
53

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.
54

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. This type of base is suitable for systemically active drugs.
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, particularly if they
contain. High solubility of macrogols which can lead to a super
saturated solution in the water and subsequent crystallisation and
this the mass granular and brittle.
55

DISADVANTAGES OF MACROGOLS
4. Crystal growth of certain medicaments may occur particularly if
they are partly in solution and partly in suspension in the base.
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 and dissolve
certain plastics necessitating care in choosing containers.
56

3.WATER - DISPERSIBLE BASE:
 Several non-ionic surface active materials, closely related
chemically to PEG as suppository bases.
 The bases can be used for formulation both water-soluble and oil-
soluble drugs (e.g.; Tween & Span).
 These surface active agents may be used alone, blended or used
in combination with other suppository vehicle.
 Another type of water dispersible suppository vehicle is based on
the use of water soluble cellulose derivatives (e.g. methylcellulose
& Sod.CMC)
57

ADVANTAGES OF WATER DISPERSIBLE BASES:
1. Stable on storage at elevated temperature.
2. Compatible with many drugs.
3. Non support of microbial growth, non toxic and non sensitive.
58

59
(B) ANTI OXIDANTS
 It protect the drugs and bases from getting degraded due to
oxidation.
 These are commonly used in all types of suppositories.
EXAMPLES-
 Ethyl or propyl gallate
 Ascorbic acid
 Butylated hydroxy anisole (BHA)
 Butylated hydroxy toluene (BHT)
 Hydroquinone
 Tocopherol

60
(C) EMULSIFYING AGENTS
 These increase the water absorbing capacity of fatty bases.
 EXAMPLES
 Poly sorbates (TWEEN 61)
 Wool alcohol
 Wool fats

61
(D) HARDENING AGENTS
 These are involved in those formulation where the melting point
of the bases is decrease by the drugs.
 These are the agents which are used to bring the melting point to
normal.
 EXAMPLES
 Beeswax
 Macrogols at high molecular weight.

62
(E) PRESERVATIVES
 These are the agents which are used in prevent the growth of
microbial in suppository which contains water soluble bases.
 EXAMPLES
 Chorocresol
 Methyl paraben
 Propyl paraben

63
(F) THICKENING AGENTS
 These are the agents which are used to increases the viscosity of
molten bases and prevent sedimentation of suspended in solid
bases.
 EXAMPLES
 Aluminium monostearate
 Colloidal silica
 Magnisium stearate
 Steary alcohol

64
(G) PLASTICIZERS
 These are the agent which are used to improved flexibility of
suppositories.
 It is also used to make the less brittles to suppositories.
 EXAMPLES
 Castor oils
 Glycerine
 Glycol
 Tween 80
 Tween 85

METHOD OF MANUFACTURE OF
SUPPOSITORIES:
1- Hand Molding:
 It is the oldest and simplest method, by rolling the suppository into
the desired shape. The mass is then rolled into a cylindrical rod of
desire length and diameter.
65
STEPS INVOLVED IN HAND MOLDING
 The drugs and other additives are made into a fine powder .
 It is incorporated into the suppository base by kneading with it or by trituration
in a mortar.
 Then these masses are rolled into the shape of a cylindrical rod on the rolling
tile in presence of lubricants to prevent the adherence of masses.
 Then cut the rods and made one end to pointed.

DRUG+ADDITIVES FINE POWDER
MIXED IN BASES
APPLY LUBRICANTS ON ROLLING TILE
ABOVE MASSES ARE ROOLED IN CYLINDRICAL SHAPE
CUT THE RODS
PACKED
STORED 66

2- COMPRESSION MOLDING:
 Elegant suppository can be made compression the cold-grated mass into the
desired shape .
 simple and more elegant appearance than hand molding.
 Avoids the possibility of sedimentation of the insoluble solids in the
suppository base.
 ADVANTAGE-
 It is suitable for thermolabile drugs because in this method no heat is
required.
 Rate of production is more.
 DISADVANTAGE-
 The main disadvantage is air entrapment occurs during production so
oxidation takes place in suppository.
67

PROCEDURE
MIXED WITH BASES
LUBRICANTS APPLY IN MOLDS
PLACED THE MASSES IN CYLINDER
APPLY PRESSURE
RELEASE SUPPOSITORY
COOLED PACKED STORED 68

3- Pour Molding (Heat molding)
 Most commonly used method for production of suppository on
both small & large scale.
 First, the base is melted on water bath, and then the drugs are either
emulsified or suspended in it. Then, the mass is pour into cooled
metal molds, which are usually chrome or nickel plated.
69

MELTING THE BASES DRUGS
FINE POWDER
TRITURATE
WITH WARM WATER
LIQUIDS
MIXED ½ PARTS OF LIQUIDS
MIXING PROPER
ADD REMAINS LIQUIDS
70

CONT……
APPLY THE LUBRICANTS IN MOLD
OVERFILLING OF MASSESIN MOLDS
REMOVE THE EXTRA MASSES
COOLING (10-15MIN)
OPEN MOLDS
PACKED
STORED
71

4 - Automatic Molding Machine:
 All the operations in pour molding are done by automatic
machines.
 Using this machine, up to about 10,000 suppositories per hour
can be produced.
 By this the rate of production of suppositories is more higher
than hand molding.
 In this ,there are no chance of air entrapment and contamination
of suppositories.
 In this ,if any mass deposited in mold is not removed during
cleaning, so produce overweight suppositories with mold marks
72

There are two types of machines used they are following---
(a) Rotary Machine-
 The rate of production of suppositories are about 3500-6000/hr.
 This machine consists of a turn table in which metal molds are
fitted.
 This table rotates sequentially, the mold gets filled with drug ,
additives, bases and cooled and ejects the suppositories.
 Before mass filled in mold ,the lubricant are apply in mold wall.
 The excess mass is removed by the scraping unit.
 The cooling system results the solidification of suppositories.
After the cooling the mold is moves towards ejection station , it
consists of a stainless steel rod which push out the suppositories
from molds.
 Then completed the ejection process , the empty molds are again
moves towards the filling unit for further processes.
73

MELT BASES + POWER
HOPPER
LUBRICATED THE MOLDS
FILLABOVE MIXTURE IN MOLD
COOLING SYSTEM
EJECTION SYSTEM
PACKED STORED
74

(B) LINEAR MACHINE
 It is similar to rotary machine.
 Except the rate of production is more higher than rotary
machine about 10000/hr.
 All steps involved is similar to rotary machine.
 There is no chance of air entrapment and contamination of
suppositories as similar to rotary machine.
 The rate of production is higher than rotary machine.
75

PREPARATION OF SUPPOSITORIES - MOULDS
76

SPECIFIC PROBLEMS IN
FORMULATING SUPPOSITORIES :
1- Water in suppositories:
Use of water as a solvent should be avoided:
Reasons:
 Water accelerates oxidation of fats.
 If water evaporates, the dissolved substance crystallizes out.
 Unless H2O is present at level than that requires for dissolving the
drug, the water has little value in facilitating drug absorption.
Absorption from water containing suppository enhance only if an
oil in water emulsion exist with more than 50% of the water in the
external phase .
78

 Reaction between ingredients (in suppository) are more likely to
occur in the presence of water.
 The incorporation of water or other substances that might be
contaminate with bacteria or fungi necessitates the addition of
bacteriostatic agents (as parabens)
79

2- Hygroscopicity:
 Glycerinated gelatin suppositories lost moisture by evaporation in
dry climates and absorbed moisture under conditions of high
humidity
 PEG bases are also hygroscopic.
80

3- Incompatibilities:
a- PEG bases are incompatible with silver salt, tannic acid,
aminopyrine , quinine , icthammol, asprine , benzoc.aine &
sulphonamides .
b- Many chemicals have a tendency to crystallize out of PEG, e.g.:
sodium sarbital, salicylic acid & camphor.
c- Higher concentration of salicylic acid softens PEG to an ointment-
like consistency, d- Aspirin complexes with PEG.
e- Penicillin G , although stable in cocoa butter and other fatty bases ,
was found to decompose in PEG bases .
f- Fatty bases with significant hydroxyl values may react with acidic
ingredients.
81

4- Viscosity:
 The viscosity of the melted suppository base is important in the
manufacture of the suppository and to its behavior in the rectum
after melting.
 Melted cocoa butter have low viscosity than glycerinated gelatin
and PEG type base in low viscosity bases, extra care must be
exercised to avoid sedimentation of suspended particles.
82

To overcome the problems caused by use of low viscosity bases:
a- Use base with a more narrow melting rang that is closer to body
temperature.
b- The inclusion of approximately 2% aluminum monostearate not
only increase the viscosity of the fat base but to maintain
homogenous suspension of insoluble material.
c- Cetyl , stearyl or myristyl alcohols or stearic acid are added to
improve the consistency of suppositories .
83

5- Brittleness :
Suppositories made from cocoa butter are elastic and don't fracture
readily.
Synthetic fat base with high degree of hydrogenation and high
stearate content and a higher solids content at room temperature are
usually more brittle.
To overcome:
1) the temperature difference between the melted base & the mold
should be minimal.
2) Addition of small amount of Tween 80, castor oil, glycerin imparts
plasticity to a fat
84

85
6- Volume contraction:
Occurs in many melted suppository base after cooling the mold,
result in:
 Good mold release (contraction facilitate the removal of the
suppository from the mold , eliminating the need for mold release
agents).
 Contraction hole formation at the open end of the mold, this will
lowered suppository . The contraction can be eliminated by pouring
a mass slightly above its congealing temperature into a mold
warmed at about the same temperature or the mold is overfilled so
that the excess mass containing the contraction hole can be scraped
off.

Lubricant or mold releasing agent:
Cocoa butter adhere to suppository molds because of its low volume
contraction. A various mold lubricants or release agents must be
used to overcome this difficulty (mineral oil , aqueous solution of
sodium lauryl sulfate , alcohol , silicones , soap). The release of
suppository from damaged mold was improved by coating the
cavities with polytetrofluoroethylene (Teflone).
86

LUBRICANTS FOR USE WITH
SUPPOSITORY
BASES:
Base
• Theobroma
oil
• Glycerol-
gelatin
base
Lubricant
• Soap spirit
• liquid
paraffin
No lubricant
required
• Synthetic
fats
• Macrogols
87

7- Rancidity and Antioxidant:
Rancidity results from the autoxidation and subsequent
decomposition of unsaturated fats into low & medium molecular
weight saturated & unsaturated aldehydes , ketones and acids ,
which have strong unpleasant odor. Example of effective
antioxidant are phenols such as " hydroquinone or B-
naphtholquinone.
88

DOSAGE REPLACEMENT FACTOR
The amount of base that is replaced by active ingredient in
suppository formulation can be calculated. The replacement factor
(f) is derived from the following equation:
F=100(E-G)+1
Where:
E= weight of pure suppository base.
G= weigh of suppositories with x% active ingredient.
89

WEIGHT AND VOLUME CONTROLE:
The amount of active ingredient in each suppository depends on:
1 . Its concentration in the mass.
2. The volume of the mold cavity.
3. The specific gravity of the base.
4. The volume variation between molds (within 2% of the desired
value).
5. Weight variations between suppositories due to inconsistencies in
the manufacturing process. e.g. incomplete closing of molds,
uneven scrapings (variations in weight should be within ± 5%)
90

EVALUATION OF SUPPOSITORY
 Melting range test
 Softening time test
 Breaking test
 Disintegration / dissolution test
91

1) MELTING RANGE TEST:
 Also called the macromelting range test & is a measure of time
which takes for entire suppositories to melt when immersed in a
constant temperature 37◦C water bath.
 Micromelting range test is the melting range measured in capillary
tubes for fat base only.
 The suppository melting point apparatus consist of graduated tube
like glass chamber. The sample to be tested is placed in spiral
shaped glass test basket inside test chamber i.e. surrounded by water
jacket heated by circulation thermostat. Time for the entire
suppository to melt or disperse in the surrounding water is
measured.
92

2. SOFTENING TIME TEST
 Softening time test apparatus consists of a U- tube partially
submersed in a water bath. A constriction on one side holds
suppository in place in the tube.
 A glass rod is placed on top of suppository & time to pass through
constriction is recorded as softening time i.e carried out at various
temp. 35.5-37◦C.
 A water bath both cooling & heating elements should be used to
assure control within 0. 1◦C.
 The penetration tester(PM 30) has been designed to carry out
reproducible measurements of softening time of suppository at
predetermined temp.
 Construction of tester makes visual observation of melting
characteristics extremely simple & unit comprises 3 test station.94

3) 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 37◦C 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.
95

4) DISINTEGRATION DISSOLUTION TESTING:
 In an effort to control the variation in mass/medium interface,
various means have been employed including wire mesh basket or
membrane to separate sample chamber from reservoir.
 Sample sealed in dialysis tubing or natural membranes have also
been studied.
 Flow cell apparatus have been used holding the sample in place
with cotton, wire, screening & most recently with glass beads.
 The basic suppositories disintegration tester complies with the latest
specifications.
97

PACKAGING OF SUPPOSITORY
 Suppository must be placed in a container in such a manner that
they do not touch each other.
 Staining, breakage or deformation by melting caused by adhesion
can result from poorly wrapped packaged suppository. Suppository
is foiled in tin or Al paper and plastic.
 Over wrapping is done by hand or machine. Many suppositories
are not individually, wrapped. In such cases, they are placed into
cardboard boxes or plastic containers that have been molded to
provide compartment for 6 or 12 suppositories.
98

IN- PACKAGE MOLDING:
A significant advance in suppository manufacturing was the
development of automated method for molding suppository,
directly in their wrapping materials. This is currently accomplished
with either plastic or Al-foil.
*ADVANTAGE OF INPACKAGE MOLDING:
1. high production rate.
2. no generation of scraping.
3. no bulk handling.
4. maintenance of strict temperature control
99

STORAGE
 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.
100

Displacement value:
The number of parts by weight of drug that displaces one part of
base.
Calculation of DV:
1. Wt. of 6 CB suppository, WCB
2. Wt. of 6 medicated(40%) suppository, WMS
3. Wt. of drug in suppository, WD = WMS x 40/100
4. Wt. of CB in suppository, WB = WMS – WD
5. Wt. of CB displaced by drug, WDCB = WCB – WB
6. Displacement value, DV = WD /WDCB
101

Q) Prepare six suppositories each containing 250 mg bismuth
subgallate.
 Quantities are calculated for an excess of two
suppositories. Therefore calculate for eight suppositories.
 DV of bismuth subgallate = 2.7
 A l g mould will be used with mould calibration = 0.94.
To calculate the amount of base required, a simple equation
is used:
Amount of base = (N x y) – (N x D/ DV)
N=8 y = 0.94 D = 250 mg = 0.25 g DV = 2.7
Amount of base required
= (8 x 0.94) –((8x0.25)/2.7) = 7.52-0.741 = 6.779 9 = 6.78
g
103

Calculations for more than one drug:
Calculate the quantities required to make 15 suppositories
each containing 150 mg hamamelis dry extract and 560 mg
of zinc oxide. A 2g mould, with mould calibration of 2.04,
will be used. Calculate for 17 suppositories (2 excess).
DV of hamamelis dry extract = 1 .5, DV of zinc oxide = 4.7.
Weight of hamamelis dry extract = 17 x 0.15 = 2.55 g.
Weight of zinc oxide = 17 x 0.56 = 9.52 g.
Weight of base = 17 x 2.04- (2.55/1.5 + 9.52/4.7) = 34.68-
(1.7 + 2.03) = 30.95 g.
104

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