Suppositorie

Suppositories :
Syllabus
Ideal requirements
Bases
Manufacturing procedure,
Packaging and
Evaluation.

 Definition :-

suppositories are semi solid

dosage form meant to be inserted
into body cavity other than mouth
like rectum, urethra, vagina where
they melt, soften or dissolve to
release the drugs and exert local or
systemic effect.

Body orifices for using

Suppositories are commonly employed rectally,

vaginally and occasionally urethrally.

They have various shapes and weights

depending upon the density of the base and

the medicaments present in it, and the
individual manufacturer's product.

Types of Suppositories
Rectal suppositories
Pessaries / Vaginal Suppositories
Urethral Suppositories or bougies
Nasal Suppositories or Nasal bougies
Ear cones or Aurinaria.

Rectal
using

Vaginal
using

Shapes available : conical, bullet,

torpedo, oviform, pencil shaped,
globular etc.
Shape of suppositories

RECTAL SUPPOSITORY
Intended for local action to relieve constipation, irritation,

itching and inflammatory associated to hemorrhoids.

To promote defecation.
Introduce drugs into the body.
Treat anorectal diseases.
Drugs employed: analgesics, antispasmodics, sedatives,

tranquilizers, antibacterial agents.

7

URETHRAL SUPPOSITORY
Also

called as BOUGIES .
SHAPE slender, pencil-shaped.
Intended for anti-bacterial or as a local
anesthetic preparative for urethral examination.
Occasionally used.

VAGINAL SUPPOSITORY
They

are also called as PESSARIES.

SHAPE : globular, oviform or cone-shaped.
Used occasionally.
Intended for local effects like contraceptives,
antiseptics in feminine hygiene

 General Size:

Rectal 2 gm (Adults)
1 gm (Children)
Pessaries (Vaginal Suppositories) 3-5

gm
Bougies (Urethral Suppositories)
4 gm and 100-150 mm long For
Males
2 gm and 60-75 mm long for females

 Nasal suppositories: - called nasal

bougies or buginaria meant for

introduction in to nasal cavity.
They are prepared with glycero gelatin
base.
They weigh about 1 gm and length 9-10
cm

Character of
action
1)Local
Action

Rectal suppositories are most frequently employed to relieve constipation

or the pain, irritation, itching, and inflammation associated with

hemorrhoids or other anorectal conditions.
Vaginal suppositories or inserts are employed mainly as contraceptives,

antiseptics in feminine hygiene, and as specific agents to combat an

invading pathogen.
Urethral suppositories may be used as antibacterial and as a local

anesthetic preparative to urethral examination.

Locally active drugs include astringents, antiseptics, local anesthetics,
vasoconstrictors, anti-inflammatory.
soothing and protective agents and some laxatives.

2)Systemic
Action
administered rectally in the form of suppositories for systemic effects include:
(a) For the relief of nausea and vomiting and as a tranquilizer
(b) For narcotic analgesia
(c) For the relief of migraine syndrome
(d) Anti-inflammatory analgesic and antipyretic.
(e) Anti-asthmatics, anti rheumatics.

a)
b)
c)
d)
e)
f)

Examples of drugs administered

rectally in the form of suppositories for
their systemic effects include
prochlorperazine
chlorpromazine
oxymorphone HCl
ergotamine tartrate
indomethacin
ondansetron

advantages over oral therapy

(rectal route for achieving
systemic
effects
)
(a) drugs destroyed
or inactivated
by the pH or enzymatic
activity of the stomach or intestines need not be exposed
to these destructive environments;
(b) drugs irritating to the stomach may be given without
causing such irritation;
(c) drugs destroyed by portal circulation may bypass the liver
after rectal absorption (drugs enter the portal circulation
after oral administration and absorption);

Absorption of Drugs from Rectum

Proper Insertion of Suppository in Rectum

(d) the route is convenient for

administration of drugs to adult or
pediatric patients who may be unable
or unwilling to swallow medication;
(e) it is an effective route in the
treatment of patients with vomiting
episodes.

Advantages of Suppositories

Advantages
Avoid firstpass
metabolism

ADVANTAGES
EASILY ADMINSTERED

to children, old
persons, to unconscious or sometimes to mentally
unstable persons who cannot swallow the drug.
Convenient mode of administration for drugs
which irritate the GIT, causing vomiting and
destroyed in acidic ph of stomach and enzymes of
GIT.
FASTER ONSET OF ACTION as compared to
oral administration because absorption of drug
through rectal mucosa directly reaches blood
20

Advantages .

1. Alternate dosage form for the drugs with

2.
3.
4.
5.

less bioavailability when taken orally.

Drugs having bad odour & taste.
For treating vomiting patients
Site- specific action on rectal, urethra,
etc
Administration of drugs which are
destroyed by portal circulation.

Disadvantages of Suppositories

Disadvantages :-

1. Not much acceptable by patient.

2. Manufacturing process is difficult.
3. Drug which cause irritation to

mucous membrane cant be

administered
4. Leakage of suppository occurs upon
insertion into the body cavity at
elevated temperature.

Disadvantages..

Slow and incomplete absorption.

Inter and intra-subject variation.
Development of proctitis.
Problems with large scale production of
suppositories and of achievement of a
suitable shelf life
5. Demanding stringent storage conditions
as Maintenance of temperature is difficult
as Most of the suppositories should be
stored at low temperature10-20c in a
refrigerator , other wise the base gets
liquefied.
1.
2.
3.
4.

Requirements to suppositories:
Rejections in-bulk suppositories must not exceed 5

%.
Medicinal matters which are contained in them are to
be exactly dosed.
Suppositories must have correct and accordingly
identical form, homogeneous mass, sufficient hardness
(mechanical durability) and fuse at the temperature of
body.
Suppositional mass must be homogeneous, without
inclusions, marbling, and sequins.

Requirements to suppositories

Time of melting (for suppositories on hydrophobic

bases) 15 minutes
Time of dissolution (for suppositories on hydrophilic
bases) 60 minutes
Length of rectal suppositories must be from 2.5 to 4
centimeters.
A maximal diameter of rectal suppositories is 1.5
centimeters.
Mass of rectal suppositories is from 1.50 to a 4.0 g
(middle 3.0).
Mass of vaginal suppositories must be from 1.5 to a
6.0 gram (middle 4.0).

Some factors of drug

absorption from rectal
suppositories
1) Physiologic factors
Colonic content
when deemed desirable, an
evacuant enema may be
administered and allowed to act
before the administration of a
suppository of a drug to be
absorbed.
Diarrhea, colonic obstruction,

Circulation route
The lower hemorrhoidal veins
surrounding the colon receive
the absorbed drug and initiate its
circulation throughout the body,
bypass the liver.
Lymphatic circulation also
assists in the absorption of
rectally administered drugs.

pH of the rectal mucosa

pH of rectal mucosa is 6.8.
Rectal fluids have no buffer
capacity.
Dissolved drugs determine the
pH of the anorectal area.
Weaker acids and bases are more
readily absorbed than the
stronger , highly ionozed ones.
Lower pH influence increased
absorption of acidic drugs but

2) Physicochemical factors of the

drug and suppository base
Lipid-water solubility
A lipophilic drug that is
distributed in a fatty suppository
base in low concentration has
less of a tendency to escape to
the surrounding aqueous fluids
than would a hydrophilic
substance present in a fatty base
to an extent approaching its
saturation.

Water soluble bases, for example,

PEG, which dissolve in the
anorectal fluids, release for
absorption both water-soluble
and oil-soluble drugs.

Naturally, the more drug a base

contains, the more drug will be
available for potential
absorption.

Particle size
For drugs present in a
suppository in the undissolved
state, the size of the drug
particle will influence its rate of
dissolution and its availability for
absorption.
The smaller the particle size, the
more readily the dissolution of
the particle and the greater the

Nature of the base

The possiblity of chemical and/or
physical interactions between the
medicinal agent and the
suppository base, which could
affect the stability and/or
bioavailability of the drug.
If the base is irritating to the
mucous membranes of the
rectum, it may initiate a colonic
response and prompt a bowel
movement, negating the prospect
of complete drug release and

3. Suppository bases and

Adjuvants

One of the first requisites for a

suppository base is that
it remains solid at room
temperature
but softens, melts or dissolves
readily at body temperature
so that the drug it contains may
be made fully available soon
after insertion.

Adjuvants

Adjuvants in the formula can affect

drug absorption through changes in
the rheologic properties of the base at
body temperatures.

Emulsion type bases: Prolonged drug

release by the addition of an aqueous
polymer.

Liophobic bases: salicylates improve

rectal absorption of water-soluble
antibiotics.

Formulation :-

Formulation includes ;
1. Suppository bases.
2. Active ingredients.
3. Additives.
Anti- oxidants
Emulsifying agents
Hardening agents
Preservatives
Thickening agents
Plasticizers

1. SUPPOSITORY BASES
As with the ointment bases,
suppository base
composition plays an
important role in both the
rate and extent of release of
medications.
Suppository bases may be
classified according to their
composition and physical
properties:
1- Oleaginous (fatty)
bases
2- Water soluble or
miscible bases
37
3- Miscellaneous
Bases

Specifications of suppository
bases
1- Origin and chemical
composition
The source of origin (i.e. entirely
natural or synthetic or modified
natural).
Physical and chemical
incompatibilities with additives
(i.e. preservatives, antioxidants
and emulsifiers) from its
chemical make up.

38

Specifications of suppository
bases
2- Melting range
Since fats (complex mixtures of triglycerides) do
not have sharp melting point, their melting
characteristics are expressed as a range indicating
the temperature at which the fat start to melt and
the temperature at which it is completely melted.
Method: USP Method, Wiley melting point,
capillary melting point, softening point, incipient
melting/Thaw point.
Example : Cocoa Butter 30-350C, Massuppol 34370C.
39

Specifications of
suppository bases
3- Solid Fat Index

Solid fat index (SFI) is a measure of the percentage of fat

in crystalline (solid) phase to total fat (the remainder
being in liquid phase) across a temperature gradient.
The SFI of a fat is measured using a dilatometer that
measures the expansion of a fat as it is heated;
density measurements are taken at a series of
standardized temperature check points.
The resulting SFI/temperature curve is related to melting
qualities and flavor.
For example, butter has a sharp SFI curve, indicating
that it melts quickly and that it releases flavor quickly.

 butter from camel milk contains a significantly

higher portion of solid fat over the entire
melting range relative to butter from cow milk

Specifications of suppository
bases
4- Solidification point
This value indicates the time required
for base solidification when it is
chilled in the mold.
If the interval between the melting range
and solidification point is 100C or more, the
time required for solidification may have to
be shortened for a more efficient
manufacturing procedure by augmenting
refrigeration.
Example: Massuppol 29.5-31.5 0C
42

Specifications of suppository bases

5- Hydroxyl Value
This is a measure of unesterified portion positions on glyceride
molecules and reflects the monoglyceride and diglyceride
content of a fat base.
The number represents the mg of KOH that would neutralize the
acetic acid used to acetylate 1 gm of fat containing free
hydroxyl groups.
The analytical method used to determine hydroxyl value traditionally
involves acetylation of the free hydroxyl groups of the
substance with acetic anhydride in pyridine solvent.
After completion of the reaction, water is added, and the
remaining unreacted acetic anhydride is converted to acetic
acid and measured by titration with potassium hydroxide.
Example: Massupol <3 (mixture of di and tri glycerides of saturated
fatty acids)

Specifications of suppository bases

6- Saponification value
The number of milligrams of potassium hydroxide required
to neutralize the free acids and to saponify the esters
contained in 1 gm of fat.
It is an indication of the type of glyceride (mono- or tri-) as
well as the amount of glyceride present.
It is a measure of the average molecular weight (or
chain length) of all the fatty acids present.
As most of the mass of a fat/tri-ester is in the 3 fatty acids, it
allows for comparison of the average fatty acid chain length.
The long chain fatty acids found in fats have a low
saponification value because they have a relatively
fewer number of carboxylic functional groups per unit
mass of the fat as compared to short chain fatty
acids.
If more moles of base are required to saponify N grams of fat
then there are more moles of the fat and the chain lengths
are relatively small.
Example: Massuppol 230-240, Cocoa butter 192-196.
44

Specifications of suppository
bases
7- Acid value
The number of milligrams of potassium
hydroxide required to neutralize the free acid
in 1 gm of substance is expressed by this
value.
Low acid values or complete absence of acid are
important for good suppository bases.
Free acids complicate formulation work, because
they react with other ingredients and can also cause
irritation when in contact with mucous membranes.
Example : Cocoa Butter 1.68 (Not Higher than 4)
45

Specifications of suppository
bases
8- Iodine value
This value express the number of
grams of iodine that react with 100
gm of fat or other unsaturated
material.
The possibility of decomposition by
moisture, acids, and oxygen (leads to
rancidity in fats) increases with high
iodine values.
Example: Massuppol <3, Cocoa
Butter 32.1135.12.

46

Specifications of suppository
bases
9- Water number
The amount of water in grams, which
can be incorporated in 100 gm of fat
is expressed by this value.
The water number can be increased
by addition of surface active agents.
Example: Massuppol 50-100.

47

1. Suppository bases
The ideal suppository base should be
Nontoxic and nonirritating to sensitive and
inflamed tissues.
Inert and compatible with a broad variety of
medicaments.
No meta-stable forms.
Can be easily manufactured by compression
or molding.
Dissolve or disintegrate in the presence of
mucous secretions or melt at body
temperature to allow for the release of the
medication.
48

 Remain molten for a sufficient period of

time to allow pouring into moulds.
Solidify sufficiently rapidly to minimize
sedimentation of dispersed solids.
Contract on cooling to allow easy
withdrawal of the suppository from the
mould.
Has wetting and emulsifying properties.
High water number.
Stable on storage, does not change color,
odor and drug release pattern.
49

If the base is fatty, it has the

following additional
requirements:
Acid value is below 0.2.
Saponification value ranges from 200
to 245.
Iodine value is less than 7.
The interval between melting point
and solidification point is small.
50

1. Oleaginous Bases
Include:
Theobroma Oil
Synthetic
triglyceride
mixtures.
51

A- Theobroma Oil or cocoa

butter
Theobroma Oil or cocoa butter is used as a
suppository base because, in large measure, it
fulfills the requirements of an ideal base.
Cocoa butter is primarily a tri-glyceride
(Oleopalmitostearin and oleodistearin chains).
It is yellowish- white, solid, brittle fat, which
smells and tastes like chocolate.
At ordinary room temperatures of 15 to 25C it
is a hard, amorphous solid, but at 30 to 35C
i.e., at body temperature, it melts to a bland,
nonirritating oil.
52

A- Theobroma Oil or cocoa

butter
Thus in warm climates, theobroma
oil suppositories should be
refrigerated.
Cocoa butter has iodine value
between 34 and 38.
Its acid value not higher than 4.

53

Disadvantages of
theobroma oil
Shrinks only slightly on solidification; a
mould lubricant is therefore required.
Exists in four polymorphic forms with
different melting points (24.0, 28.0-31.0,
34.0-35.0C and 18.0 ).
Theobroma oil should only be heated for a
short time and at temperatures below 36
C in order to minimize the formation of
the unstable low melting point forms.
54

 The change (reduction) in melting point

caused by addition of certain drugs such
as volatile oils, phenol or chloral hydrate
to cocoa butter suppositories. The solution
is to raise the melting point back to the
desired range by addition of 3% to 5% of
beeswax or spermaceti.
Theobroma oil has a low absorptive
capacity for water, but this can be
increased by adding surfactants such as
cholesterol 2%, emulsifying wax up to
10%, polysorbates 5 to 10%, or wool fat 5
to 10%. However, the addition of
surfactants may lead to a drug- base
55

Theobroma oil is prone to oxidation

(due to high iodine value); this can
be partly overcome by storage in a
cool, dark place.
Theobroma oil may vary in
consistency, odor, and color
depending on its source like other
natural products.
The low melting point of theobroma
oil may pose storage problems in hot
56

 Emulsified Theobroma Oil: to incorporate large quantity

of aqueous solutions.
5% Glyceryl monostearate, 10% lanette wax, 2-3% cetyl
alcohol, 4% bees wax and 12% spermaceti is recommended
to prepare emulsified Theobroma oil suppository.
Hydrogenated Oil: Hydrogenation of various vegetable
oils like coconut oil, cotton seed oil, palm oil etc used as
substitute for theobroma oil.
Advantages:
Resistant to oxidation.
Mold lubrication not required.
solidification point not affected by overheating.
produce colourless, odourless and elegant suppositories.
good emulsifying and water absorbing capacities.
Disadvantages
Become brittle on rapid cooling.
More fluid than theobroma oil which is overcome by
bentonite or magnessium stearate.

B- Synthetic Tri-glycerides (hard fat)

The newer synthetic tri-glycerides
consist of esterified, hydrogenated or
fractionated vegetable oils.
Their advantages over cocoa butter
are:
1- Do not exhibit polymorphism.
2- Contain mainly saturated acids (Iodine
number <3), while cocoa butter contains
considerable amount of the unsaturated
fatty acids (Iodine number 34-38).
58

B- Synthetic Tri-glycerides (hard fat)

3- The melting range of the synthetic
bases is usually about 3C higher than
that of cocoa butter
4- The acid content is lower (mostly <0.5)
5- hard fat is a mixture of mono, di and triglycerides of saturated fatty acids (C 10
to C18). The hydroxyl value of a base is
determined by the proportions of mono
and di-glycerides contained in it.
A higher hydroxyl value indicates that the
base can absorb water more readily and
less suitable to easily hydrolyzed drugs.
59

B- Synthetic Tri-glycerides (hard fat)

6- The solidification temperatures of hard
fats are unaffected by over heating.
7- There is only a small temperature
difference between melting and
solidification, thus the sedimentation of
suspended drugs is minimized.
8- Mold lubrication is unnecessary since
these bases show marked contraction on
cooling.
9- The water absorbing capacity of hard fats
can be improved (to about 25% or 30%
w/w) by inclusion of glyceryl
60
monostearate.

B- Synthetic Tri-glycerides (hard fat)

They are, however, more expensive.
A tendency to fracture upon pouring into
chilled moulds can be overcome by
including very small quantities of
polysorbate 80.
On prolonged storage, synthetic
suppository bases have been shown to
be subjected to crystallization, which
causes hardening and increases the
melting time. This can be reduced by
storage in a cold place.

61

B- Synthetic Tri-glycerides (hard fat)

The hard-fat alternatives to theobroma
oil are available in various grades with
different melting ranges, hydroxyl values
and other physicochemical
characteristics.
Some of the bases are single entity
formulations.
Some of the names may denote a series
of bases.
In a series, the bases are varied to give a
range of melting points.
62

 For example, Fattibase is a single

entity base that consists of triglycerides
from palm, palm kernel, and coconut
oils.
Wecobee is a series of bases.
Wecobee FS, M, R, and S are all made
from triglycerides of coconut oil. But FS
has a melting point range of 39.4 to
40.5C, M has a range of 33.3 to 36.0C,
R has a range of 33.9 to 35.0C, and S
has a range of 38.0 to 40.5C.
Other triglyceride type bases include
Dehydag, Hydrokote, Suppocire,
and Witepsol, Massuppol.
63

Selection of a Suppository Base

Narrow interval between melting range and
solidification point.
High melting ranges (37-41 0C) for incorporation of
drugs that lower melting points of bases. Ex:
Chloral Hydrate.
Low melting ranges (30-34 0C) when the substances
added or large amount of total solids increase the
viscosity of the molded suppository.
Low acid values (<3) and iodine values (<7)
essential for long intended shelf-life.

2. Water Soluble/Water
Miscible Bases

Water
Soluble/Water
Miscible Bases
are those
containing:
A. Glycerinated
gelatin
B. Polyethylene
glycol (PEG)
polymers.
65

A- Glycerinated Gelatin
Glycerinated Gelatin is a useful
suppository base, particularly for vaginal
suppositories, where the prolonged
localized action is usually desired.
Glycerinated gelatin suppositories are
translucent, resilient, gelatinous solids
that tend to dissolve or disperse slowly in
mucous secretions to provide prolonged
release of active ingredients.
It is suitable for use with a wide range of
medicaments including alkaloids, boric
acid, and zinc oxide.
66

 Suppositories made with glycerinated

gelatin must be kept in well-closed
containers in a cool place since they will
absorb and dissolve in atmospheric
moisture.
Suppositories may have a dehydrating
effect and be irritating to the tissues
upon insertion. The water present in the
formula of suppositories minimizes this
action and the suppositories may be
moistened with water prior to insertion
to reduce the tendency of the base to
67
draw water from mucous.

In addition, those suppositories

intended for extended shelf-life
should have a preservative added,
such as methylparaben or
propylparaben, or a suitable
combination of the two.
To facilitate administration,
glycerinated gelatin suppositories
should be dipped in water just before
use.

68

Preparation of glycerinated gelatin

rectal suppositories
Mix or dissolve the medicaments in water
to make a total of 10 g.
Add 70 g of glycerin and mix.
Add 20 g of granular gelatin, mix carefully
to avoid incorporation of air.
Heat on a steam bath until the gelatin is
dissolved.
Pour the melted mixture into molds and
allow to congeal.
69

Preparation of glycerinated gelatin

urethral suppositories
The gelatin constitutes about 60% of
the weight of the formula, the
glycerin about 20%, and the
medicated aqueous portion about
20%.

70

B- Polyethylene Glycol
Polymers
Polyethylene Glycol Polymers have

received much attention as suppository

bases in recent years because they
possess many desirable properties.
They are chemically stable, nonirritating,
miscible with water and mucous
secretions, and can be formulated, either
by molding or compression, in a wide
range of hardness and melting point.

71

Like glycerinated gelatin, they do not melt

at body temperature, but dissolve to

provide a more prolonged release than
theobroma oil.
Certain polyethylene glycol polymers may
be used singly as suppository bases but,
more commonly, formulas call for
compounds of two or more molecular
weights mixed in various proportions as
needed to yield a finished product of
satisfactory hardness and dissolution time.
72

PEGs having average molecular weights of

200, 400 and 600 are clear, colorless
liquids.
Those having molecular weights of greater
than 1000 are wax-like, white solids with
hardness increasing with an increase in
the molecular weight.
Since the water miscible suppositories
dissolve in body fluids and need not be
formulated to melt at body temperature,
they can be formulated with much higher
73
melting points.

This property permits a slower release of

medicaments from the base, safe storage
at room temperature without need for
refrigeration, and ease and slow insertion.
To prevent irritation of the mucous
membranes after insertion of PEGs
suppositories, they should contain at least
20% of water or dipped in water just prior
to use.

74

Examples of various PEGs used in suppository bases

1450
8000

30%
70%

300
6000

48%
52%

300
8000

60%
40%

1000
3350

95%
5%

1000
3350

75%
25%

75

3. Miscellaneous Bases
Chemical or physical Mixtures of
oleaginous and water soluble or water
miscible materials.
Emulsions, generally of w/o type (i.e.
mixing of cocoa butter with emulsifying
agents).
Polyoxyl 40 stearate is a mixture of the
mono-stearate and di-stearate esters of
mixed poly-oxyethylene diols and the free
glycols.
Soap may be used as a base (i.e. Glycerin
suppositories, USP, with soap as the base).76

Special Characteristics of Different Bases

Cocoa butter remains solid at room temperature but melts in the body.

Synthetic hard fat has good water absorbing capacity due to presence of w/o
emulsifying agent .

Glycero-gelatin produce laxative effect.

Polyethylene glycols are present in different physical state.

(solid, semisolid, liquid )

2.Anti-oxidants
They protect the drug and the base
from getting degraded due to
oxidation.
Examples :
i. Ethyl or propyl gallate
ii. Ascorbic acid and its esters
iii. Hydroquinone
iv. Tocopherols
78

3.Emulsifying agents:
They increase the water-absorbing capacity of fatty bases.
This makes it possible to include aqueous solutions in the
formulation.
Examples : polysorbates (tween 61)
Wool alcohol ,wool fat
4. Hardening agents:
These are included in those formulations where the melting
point of the base is decreased by the drug (Volatile oil,
phenol, chloral hydrate.)
79

These agents bring the melting point to normal.

Examples : macrogols with high molecular
weight.
5.Preservatives : They should be included in
suppositories which contain water soluble bases
to prevent microbial growth.
Examples :methyl paraben , propyl paraben
6.Thickening Agents: They increase the
viscosity of molten base and prevent
sedimentation of suspended insoluble solids.
Examples: Aluminium monostearate ,collodial
silica ,magnesium stearate.
80

7.Plasticizers :
They impart plasticity to the fatty base and
makes it less brittle.
Examples :
i. Castor oil
ii. Glycerine or propylene glycol
iii. Glycol
iv. Tween 80
v. Tween 85
81

Preparation of Suppository

Hand Rolling
Compression Molding
Pour/ Fussion Molding
Automatic Molding

METHODS OF PREPARATION
Suppositories can be extemporaneously
prepared by one of three methods.
1. Hand Rolling
It is the oldest and simplest method of
suppository preparation and may be
used when only a few suppositories are
to be prepared in a cocoa butter base.
It has the advantage of avoiding the
necessity of heating the cocoa butter.
A plastic-like mass is prepared by
triturating grated cocoa butter and
active ingredients in a mortar.
83

Follow; 1. Hand Rolling

The mass is formed into a ball in the

palm of the hands, then rolled into a
uniform cylinder with a large spatula or
small flat board on a pill tile.
The cylinder is then cut into the
appropriate number of pieces which are
rolled on one end to produce a conical
shape.
Effective hand rolling requires
considerable practice and skill. The
suppository "pipe" or cylinder tends to
crack or hollow in the center, especially
84
when the mass is insufficiently kneaded

Hand Rolling

1. MOLDING BY HAND
STEP 3
Trituration
in pestle and
mortar

86

MOLDING BY HAND

STEP 4

Mass
Rolled
Long
rods

87

1. MOLDING BY HAND

STEP 5
Rods
cut into pieces
88

2. Compression Molding
Compression molding is a method of
preparing suppositories from a mixed
mass of grated suppository base and
medicaments which is forced into a
special compression mold using
suppository making machines.
The suppository base and the other
ingredients are combined by thorough
mixing.
The friction of the process causing the
base to soften into a past-like
89

2.COMPRESSION MOLDING
The cold mass of the base containing
the drug is compressed into suppositories
using a hand operated machine.
STEP 1

drug
fine powder
90

COMPRESSION MOLDING

STEP 2

Drug (fine powder)

Base
91

COMPRESSION MOLDING

STEP 3

Trituration
in pestle and
mortar
92

COMPRESSION MOLDING

STEP 4
Compress the
mixture in the
compression
mold

93

 On a small scale, a mortar and pestle may

be used (preheated mortar facilitate
softening of the base).
On large scale, mechanically operated
kneading mixers and a warmed mixing
vessel may be applied.
In the compression machine, the
suppository mass is placed into a cylinder
which is then closed.
Pressure is applied from one end to release
the mass from the other end into the
suppository mold or die.
94

 When the die is filled with the mass,

a movable end plate at the back of
the die is removed and when
additional pressure is applied to the
mass in the cylinder, the formed
suppositories are ejected.
The end plate is returned, and the
process is repeated until all of the
suppository mass has been used.
95

 The method requires that the

capacity of the molds first be
determined by compressing a small
amount of the base into the dies and
weighing the finished suppositories.
When active ingredients are added, it
is necessary to omit a portion of the
suppository base, based on the
density factors of the active
ingredients.

96

Advantages:
It is a simple method.
It gives suppositories that are more elegant than hand
moulded suppositories.
In this method sedimentation of solids in the base is
prevented.
Suitable for heat labile medicaments.
Disadvantages:
Air entrapment may take place.
This air may cause weight variation.
The drug and/or the base may be oxidized by this air.

3. Fusion Molding
Fusion Molding involves:
1- Melting the suppository base
2- Dispersing or dissolving the drug in the melted
base.
3- The mixture is removed from the heat and
poured into a suppository mold.
4- Allowing the melt to congeal
5- Removing the formed suppositories from the
mold.
The fusion method can be used with all types of
suppositories and must be used with most of them.

98

Fusion Molding

Suppository molds

Using a supp. mould which is made of metal or

plastic. Traditional metal moulds are in two
halves which are clamped together with a
screw.

Suppository molds
Small scale molds
are capable of
producing 6 or 12
suppositories in a
single operation.
Industrial molds
produce hundreds
of suppositories
from a single
molding.
101

3.Automatic Molding Machine

3.Automatic Molding Machine

The molding operations(pouring,
cooling, and removal) can be
performed by machine. All filling,
ejecting, and mold-operations are fully
automated. The output of a typical
rotary machine ranges from 3500 to
6000 suppositories.
The machine usually made up of
chrome-plated brass molds are
installed radially in the cooling turn
able.

Lubrication of the mold

Depending on the formulation,
suppository molds may require
lubrication before the melt is poured to
facilitate the clean and easy removal of
the molded suppository.
Lubrication is seldom necessary when
the suppository base is contracting
sufficiently on cooling.
Lubrication is usually necessary when
glycerinated gelatin suppositories are
prepared.
104

Lubricants for use with Suppository

bases
Base

105

Problems in Formulation of Suppositories

Water in suppositories.
Hygroscopicity.
Incompatibilities.
Viscosity.
Brittleness.
Density.
Volume correction.
Lubricants or mold release agents.
Dosage Replacement factor.
Weight and volume control.
Rancidity and antioxidants.
Packaging.

Water in suppositories
Water as a solvent to incorporate substances in
suppositories should be avoided for the following
reasons:
Water accelerates the oxidation of fat.
If water evaporates dissolved substances crystallize out.
Water in suppositories has little effect on drug
absorption unless in significantly higher quantity to
dissolve the drug or present as O/W emulsion.
More chances of a reaction between suppository
ingredients compared to use of anhydrous ingredients.
Incorporation of water or other possibly microbe
contaminated substances necessitates the use of
bacteriostatics such as parabens.

Hygroscopicity
Glycerinated Suppositories
Loose moisture in dry climates and absorbs in
high humid conditions.

Polyethylene Glycol Bases

Rate of moisture change depends upon humidity
and temperature.
Molecular weight/Chain length increases,
Hygroscopicity decreases ( significant drop in
4000 and 6000 series)

Incompatibilities
Polyethylene glycol bases incompatible with silver salts,
quinine, aspirin etc.
Many chemicals crystallize out of PEG. Ex: salicylic acid,
sodium barbital.
Salicylic acid soften PEG to an ointment like consistency
and aspirin complexes with it.
Penicillin G stable in cocoa butter or other fatty bases
decomposes in PEG.
High hydroxyl value fatty bases may react with acidic
ingredients.

Viscosity
Glycero-gelatins and PEGs have more viscosity than Cocoa
butter and some of its substitutes after melting.
Low viscosity bases have problems like sedimentation of
suspended particles, nonuniform distribution of active
ingredients.
For low viscosity bases:
Handling of well mixed molten mass at lowest possible
temperature in melting range to maintain fluidity but prevent
segregation of particles.
Constant stirring without entrapping air and quick
solidification in the mold.
Use of base with narrow melting range close to body
temperature.
Use of viscosity enhancers like 2% aluminum monostearate.

Brittleness
Cocoa butter produces elastic suppositories that do
not fracture readily.
Synthetic fat bases for having high degree of
hydrogenation and high stearate content, have higher
solid content in room temperature and thus brittle.
Shock cooling also results brittle suppositories.
Brittle suppositories are difficult in manufacturing,
handling wrapping and in use.
Prevention: 1. heating of mold close to melted base.
2. use of plasticizers like Tween 60,
castor oil, glycerin, Propylene Glycol etc

Density
The volume of mold cavity is fixed.
The weight of individual suppository depends
upon the density of the mass and volume of given
mold.
The amount of drug in each molded suppository
should be carefully maintained the same.
Compensate for volume contraction.
Determination of suppository weight empirically
by small batch runs when volume contraction
occurs.

Calibration of the mold

Each individual mold is capable
of holding a specific volume of
material in each of its openings.
The pharmacist should calibrate
each suppository mold for the
usual base so as to prepare
medicated suppositories each
having the proper quantity of
medicaments.

volume contraction
Occurs in case of many suppository
bases:
This may cause
1. Good mold release without the need of
mold release agents.
2. Formation of contraction hole at the open
end of the mold. This can be avoided by
compensation or overfilling and scrapping
of the congealed excess base at the top.

Lubricants or Mold Release Agents

Bases with low volume contraction like cocoa
butter are difficult to remove .
Need of lubricants like: mineral oil, aqueous
solution of SLS, silicones, alcohols etc.
Method of application of lubricants: wiping,
brushing or spraying.
Teflon coating of damaged mold cavities improves
suppository release from them.

Dosage Replacement factor

Using cocoa butter as base.
Determination of the dosage replacement factor
method
f={100(E-G)/GX}+1
where E=the weight of the pure base
suppositories
G=the weight of suppositories with X% of the
active ingredient
Example: Boric Acid 0.67.
castor oil 1.
ZnO 0.15-0.25.
Camphor 1.49.

Weight and volume control

The amount of active ingredients in each
suppository depends upon
1. Concentration in the mass.
2. Volume of mold cavity.
3. Specific cavity of the base.
4. Volume variation between mold due to
manufacturing of molds (within 2%).
5. Weight variation between suppositories due to
inconsistent manufacturing i.e., incomplete
closing of the mold and uneven scrapping etc.
6. Variation of suppository weight should be
within 5%.

Rancidity and anti-oxidants

Auto-oxidation and subsequent decomposition of
unsaturated fats into low/medium molecular
weight saturated and unsaturated aldehydes,
ketones and acids.
Lower the unsaturated fatty acid content, greater
the resistance towards rancidity.
Rancidity is measured by formation of
hydroperoxides and presence of strong,
unpleasant odour.
Iodine test with KI measures peroxide oxygen.
Anti-oxidants used are: tocopherols, BHA,
BHT,propyl gallate and tannic acid etc.

Stability of Suppositories
Storage stability studies are conducted at 4 0C and at
room temperature (2530C) for suppository base and
the active ingredient(s).
Stability of suppositories intended for tropics are tested
in their final packages under tropical conditions
Important stability related problems includes1. Bloom.
2. Hardening of fat base suppositories upon storage.
3. Pinholes in suppository overwrap foil of an acid
containing suppository.
4. Maintaining physicochemical properties during storage
in tropical temperature (500C).
5. Shipment and handling related problems.

Labeling And Packaging

Should be Stored in a Cool Place
Special polyethylene shell packages are employed.
Glycerinated gelatin and PEG suppositories should be
protected from heat moisture and dry air by
packaging them in well sealed container an storing
them at a cool temperature.
Refrigeration.
Protection from light for photosensitive ingredients

TEST/EVALUATION
OF
SUPPOSITORIES.

Testing of suppositories
Finished suppositories are routinely
inspected for:
Appearance.
Content uniformity
Melting range test
Drug release test
Fragility test
Disintegration test
122

a) Melting Range test :Macro melting range tes

The micro melting range test .

The apparatus commonly used for measuring the melting

range of the entire suppository is a USP Tablet
Disintegration Apparatus.

Macro Melting range

test
Macro-melting

range is a measure of the

time it takes for the entire suppository to
melt when immersed in a constanttemperature (37C) water bath.

USP

tablet disintegration apparatus is

used

124

Micro Melting range test

In

contrast the micro melting range test is the

melting range measured in capillary tubes for
the fat base only.
The apparatus commonly used for measuring
the melting range of the entire suppository is a
USP Tablet Disintegration Apparatus.

125

b) Liquefaction or Softening time test:-

This test consists of a U-tube partially

submersed in a constant- temperature
water bath. A constriction on one side
holds the suppository in place in the
tube. A glass rod is placed on top of
the suppository, and the time for the
rod to pass through the constriction is
recorded as the softening time.

c) Breaking Test: To

measure the fragility or

brittleness of suppository
Double wall chamber in which the
test suppository is placed.
Water at 37C is pumped through
the double wall.
The suppository supports a disc to
which rod is attached.
The other end of the rod consist
of another disc to which weights
are applied.
12

Follow; Hardness
The

test was conducted by placing the

suppository to support the axis of 600 g
weight.
At one minute intervals 200 gm weights
are added.
The weight at which the suppository
collapses is the breaking point
When the breaking point reached in the
first 20 sec, the added weight was not
calculated
When the breaking point reached in the
second 20 sec, half the added weight
12
was calculated

d) Dissolution Test:Testing for the rate of in vitro release of drug

substances from suppositories has always posed a
difficult problem, owing to melting, deformation,
and dispersion in the dissolution medium. Early
testing was carried out by simple placement in a
beaker containing a medium.
In an effort to control the variation in mass/ medium
interface, various means have been employed
including a wire mesh basket, or a membrane, to
separate the sample chamber from the reservoir.
Samples sealed in dialysis tubing or natural
membrane have also been studied. Flow cell
apparatus have been used, holding the sample in
place with cotton, wire screening, and most recently
with glass beads.

In-vitro drug release

In-vitro drug release pattern is measured
by using the same melting rang
apparatus.
Aliquots of the release medium were taken
at different time intervals within the
melting period.
The drug content in the aliquots was
determined.
The drug release pattern was plotted (time
versus-drug release curve)

13
0

Formulation Considerations

Is the medication intended for local or

systemic use.

Is the site of application rectal, vaginal or

urethral.

Is the desired effect to be quick or slow and

prolonged.

Packaging and storage

In-Package Molding: Thermoformed Molds.

Foil/Polypropylene/Lacquer
laminated emboss two parallel strips.
If the mass should melt at high
storage temperature, ,old still retained the its proper
shape upon cooling.
Disadvantages: Shape of the formed mold and seal

Packaging and storage

Glycerin suppositories and

glycerinated gelatin
suppositories are packaged in
tightly closed glass containers to
prevent a moisture change in the
content of the suppositories.

Suppositories prepared from a

cocoa butter base are usually
individually wrapped or

Suppositories containing lightsensitive drugs are individually

wrapped in an opaque material
such as metallic foil.
Suppositories are also commonly
packaged in slide boxes or in
plastic boxes.

It is necessary to maintain
suppositories in a cool place.
Suppositories having cocoa
butter as the base must be stored
below 30C, and preferably in a
refrigerator (28C).
Glycerinated gelatin
suppositories are best stored at
temperatures below 8C and can
routinely be stored at controlled
room temperature (2025C).
Suppositories made from a base
of polyethylene glycol may be

Density (Dose
Replacement)
Calculations for
Suppositories

Dosage Factor Method.

Determination of Density Factor

Method.

Determination of Occupied Volume

Method.

Density calculations for

suppositories

Determination of the dosage

replacement factor method
f={100(E-G)/GX}+1
where E=the weight of the pure
base suppositories
G=the weight of suppositories
with X% of the active ingredient

Example 1
Prepare a suppository containing
100 mg of phenobarbital (f=0.81)
using cocoa butter as the base.
The weight of the pure cocoa
butter suppository is 2.0 g. What
will be the total weight of each
suppository?

Determination of density factor

method
1) Determine the average blank
weight, A, per mold using the
suppository base of interest
2) Weigh the quantity of suppository
base necessay for 10 suppositories.
3) Weigh 1.0 g of medication
4) Melt the suppository base and
incorporate the medication, mix,
pour into molds, cool, trim, and
remove from the molds

6 determine the density factor

as follows
Density factor = B/(A-C+B)
where
A=average weight of blank
B=weight of medication per
suppository
C=average weight of medicated
suppository
7) Take the weight of the
medication required for each
suppository and divide by the

8) Subtract this quantity from the

blank suppository weight
9) Multiply by the number of
suppositories required to obtain
the quantity of suppository base
required for the prescription.
10) Multiply the weight of drug
per suppository by the number of
suppositories required to obtain
the quantity of active drug
required for the prescription.

Example 2
Prepare 12 acetaminophen 300
mg suppositories using cocoa
butter, where the average weight
of the cocoa butter blank is 2 g
and the average weight of the
medicated suppository is 1.8 g.

Determination of occupied volume

method
1)

2)
3)

4)

Determine the average weight per

mold (blank) using the suppository
base of interest
Weigh the quantity of suppository
base necessary for 10 suppositories
Divide the density of the active drug
by the density of the suppository base
to obtain a ratio
Divide the total weight of active drug
required for the total number of
suppositories by the ratio obtained in
step 3 (this will give the amount of
suppository base displaced by the

5)

6)

Substract the amount obtained

in step 4 from the total weight
of the prescription to obtain the
weight of suppository base
required
Multiply the weight of active
drug per suppository times the
number of suppositories to be
prepared to obtain the quantity
of active drug required

Example 3
Prepare 10 suppositories, each
containing 200 mg of a drug with
a density of 3.0. The suppository
base has a density of 0.9 and a
prepared blank weighs 2.0 g.
Using the determination of
occupied volume method,
prepare the required
suppositories.