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SUPPOSITORIES
AND PESSARIES
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.
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.
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
TYPES OF
SUPPOSITORIES
• Cone or torpedo shaped weighing 1 – 2 gRectal
• 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 longNasal bougies
• Pencil shapedEar cones
SIZE OF
SUPPOSITORIES
0 For Children
1,2 & 3 For rectal
use
4 Pessaries
A & B Nasal &
urethral
bougies
SHAPE OF SUPPOSITORIES
RECTUM PHYSIOLOGY
• Terminal 15-19 cm of large intestine (LI)
• Rectal Fluids -> no buffering capacity
• 1. 2 - 3 mL
• pH 6.8
• Mild environment / drug can change pH
• LI function absorb H2O and electrolytes
• „Low surface area -> poor absorption compare SI
RECTAL BLOOD
CIRCULATION
Main blood supply
superior rectal artery
Blood return 3 blood
veins
– Superior
hemorrhoidal vein
– Middle
hemorrhoidal vein
– Inferior
hemorrhoidal vein
Superior hemorrhoidal vein
Inferior mesenteric -> Hepatic portal -> Liver
Middle and inferior
Drug goes directly into systemic circulation
No first pass metabolism by liver
Drug avoids stomach and digestive enzymes
Patient counseling -> don't place too high in rectum
LOCATION OF
SUPPOSITORY
FORMULATION
PROBLEMS IN FORMULATION
OF SUPPOSITORIES
1. Water in suppositories
Formulators do not like to use water for dissolving drugs in
suppositories for the following reasons :
a. Water causes oxidation of fats.
b. If the suppositories are manufactured at a high temperature,
the water evaporates, the drugs crystallize out.
c. Absorption of water soluble drugs is enhanced only if the
base is an oil – in – water emulsion with more than 50% of the
water in the external phase.
d. Drug excipient interactions are more likely to happen in the
presence of water.
e. Bacterial contamination may be a problem, so we may be
forced to add a preservative.
2. Hygroscopicity
Glycerogelatin suppositories lose moisture in dry climates
and absorb moisture in humid conditions
The hygroscopicity of polyethylene glycol bases depends on
the chain length of the molecule
As the molecular weight of these ethylene oxide polymers
increases the hygroscopicity decreases
3. Drug-excipient interactions
Incompatibilities exist between polyethylene glycol base and
some drugs.
Sodium barbital and salicylic acid crystallize out of
polyethylene glycol.
High concentrations of salicylic acid soften polyethylene
glycol to an ointment like consistency.
Penicillin G is stable in cocoa butter and other fatty bases. It
decomposes in polyethylene glycol bases.
4. Viscosity
When the base has low viscosity, sedimentation of the drug
is a problem.
2% aluminium monostearate may be added to increase the
viscosity of the base
Cetyl and stearyl alcohols or stearic acid are added to
improve the consistency of suppositories
5. Brittleness
Cocoa butter suppositories are elastic, not brittle
Synthetic fat bases are brittle
This problem can be overcome by keeping the temperature
difference between the melted base and the mold as small as
possible
Materials that impart plasticity to a fat and make them less
brittle are small amounts of Tween 80, castor oil, glycerin or
propylene glycol
6. Density
Density of the base, the drug, the volume of the mould and
whether the base is having the property of volume
contraction are all important. They all determine the weight of
the suppository
7. Lubrication of moulds
Some widely used lubricating agents are mineral oil, aqueous
solution of SLS, alcohol and tincture of green soap. These
are applied by wiping, brushing or spraying
8. Volume contraction
On solidification the volume of the suppository decreases. The
mass of the suppository pulls away from the sides of the mould.
This contraction helps the suppository to easily slip away from
the mould, preventing the need for a lubricating agent.
Sometimes when the suppository mass is contracting, a hole
forms at the open end. This gives an inelegant appearance to the
suppository. Weight variation among suppositories is also likely
to occur.
This contraction can be minimized by pouring the suppository
mass slightly above its congealing temperature into a mould
warmed to about the same temperature. Another way to overcome
this problem is to overfill the molds, and scrape off the excess
mass which contains the contraction hole.
9. Displacement value
The volume of suppositories from a particular mould will be
constant but the weight will vary because the densities of the
medicaments usually differ from the density of the base, and
hence the density of the medicament will affect the amount of the
base required for each suppository
10. Weight and volume control
Various factors influence the weight of the suppository, the volume
of the suppository and the amount of active ingredient in each
suppository.
They are:
1. Concentration of the drug in the mass
2. Volume of the mould cavity
3. The specific gravity of the base
4. Volume variation between moulds
5. Weight variation between suppositories due to the
inconsistencies in the manufacturing process.
The limit for the weight variation in suppositories is 5%.
11. Rancidity
The unsaturated fatty acids in the suppository bases undergo
auto oxidation and decompose into aldehydes, ketones and
acids. These products have strong, unpleasant odours
The lower the content of unsaturated fatty acids in a base, the
higher is its resistance to rancidity
DRUG
1. Should have sufficient absorption from particular body cavity (if
for systemic use)
2. Best suited for drugs undergoing first pass metabolism, degrade
in GI fluids or irritate the GI mucosa
3. Should be easily dispersible or soluble in the base
4. Should be soluble to achieve homogeneity but should not have
more affinity for the base or else it wouldn't get released
5. Particle size should be less to improve bioavailability and
decrease irritation
6. Density and solubility of the drug should ensure minimum usage
of base and formation of smaller suppositories
7. Drug should be compatible and stable in base and at processing
conditions
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
TYPES OF SUPPOSITORIES BASES
Suppository
bases
Fatty bases
Cocoa Butter
Synthetic fats
Proprietary
synthetic
bases
Water soluble
or water
miscible bases
Glycero-
gelatin
Macrogols
FATTY BASES
COCOABUTTER (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 oleopalmitostearin
and oleodistearin 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 – innocuous,
bland, and non-reactive, and melts at body temp.
Disadvantages
Polymorphism
Adherence to
mould
Low softening
point
Melting point
reduction
Deterioration
during storage
Poor water
absorbing
capacity
Leakage from
the body
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.
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.
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
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.
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
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.
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.
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.
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.
PROPRIETARY SYNTHETIC BASES
Whitepsol (formerly
called Imhausen)
• 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
with chain lengths of C11
to C17. Grade B is
recommended for general
dispensing.
Massuppol
• This differs from the
previous materials in
being single general
purpose base with only
one modification, for cold
moulding.
• 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.
WATER
SOLUBLE OR
WATER
MISCIBLE
BASES
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.
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.
Gelatin is incompatible with protein precipitants such as
tannic acid.
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.
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.
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.
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.
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.
PREPARATION
OF
SUPPOSITORIES
AND PESSARIES
3 METHODS
1. Moulding
2. Hand rolling
3. Compression
PREPARATION OF SUPPOSITORIES -
MOULDS
CLEANING OF
MOULDS
Mould
Interior –
Don’t scrap
or rub with
abrasive
Immerse in
hot
detergent
water
Wipe with
soft cloth
Rinse
thoroughly
NORMAL CAPACITIES
OF MOULDS
1g
(15gr)
2 g
(30gr)
4 g
(60gr)
8 g
(120gr)
WAYS OF PREPARING PROPRIETARY
SUPPOSITORIES – CONVENTIONAL
MOULDS
Individual
packing in
laminated
foil
Strip packing
in hermatically
sealed tight
fitting
laminated foil
or plastic film
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.
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.
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.
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
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
Industry – silicone fluid is used as lubricant.
Incompatibility between lubricant, medicament and adjuncts
should be checked.
Lubricant should be applied on pad of guaze or muslin or with
a small fairly stiff brush.
Cotton wool is unsuitable because fibres 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.
GENERAL METHODS OF
PREPARATION
Suppositories
Fatty base
Insoluble
solids
Solids soluble
in the base
Semi-solids
Liquids
White
suppositories
Glycero-
gelatin base
Macrogol
base
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.
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
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
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
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
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.
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.
SUPPOSITORIES CONTAINING SOLIDS
SOLUBLE IN BASE
When soluble substances are used there is depression in
melting point.
Product is satisfactory and quite firm.
Occasionally the suppositories become too soft to use.
To avoid this a synthetic base with higher melting should
be used. E.g Massa Estranium Type C or Witepsol E75
BPC – White beeswax (M.P: 62 to 64 °C) – complicates the
preparation when used with theobroma oil – affects the
solidifying point of the base and delays setting.
These problems can be avoided if following procedure is
followed
1. Melt the
base
2. Cool it
to
consisten
cy of thick
cream
3. Add
finely
powdered
solid
4. Stir
until fully
dissolved
5.
Proceed
in usual
way
SUPPOSITORIES CONTAINING SEMI-
SOLIDS
1. Reduce the viscosity of drug by trituration on
warm tile with enough water
2. Homogenous liquid of consistency of glycerol or
somewhat thinner is formed
3. Added water is allowed for and transfer the
dilution to the tared container
4. Add sufficient melted base to produce a weight
equal to the product of the nominal capacity of the
mould and the number of suppositories in excess
5. Mass is stirred vigorously to form a mechanical
emulsion and the preparation is completed in
normal manner
Care should be taken during stirring the mass to form mechanical emulsion
because it should not be continued before the liquid becomes somewhat
unpourable.
Satisfactory dispersion can be ensured by –
• The mixture must stirred vigorously to produce a perfect dispersion.
• Pouring must be delayed to the last possible moment so that the globules of aqueous liquid are enclosed in a
solid film fat.
In this method synthetic bases are preferred because they contain emulsifying
agents.
Water containing suppositories are susceptible to microbial growth so addition of
preservative agent is necessary.
Water may evaporate leaving cavities or creating high local concentration of drug
that cause irritation.
Failure to establish and maintain a stable emulsion during preparation may lead to
moisture seeping of the product.
SUPPOSITORIES CONTAINING
LIQUIDS
Liquids used in suppositories fall into 2 categories
1. Liquids that are volatile (e.g. volatile oils) or owe their medicinal
use to volatile constituents (e.g. peru balsam). These cannot be
evaporated. They lower the melting point of fatty base.
2. Liquids that are aqueous or hydro-alcoholic that owe their
medicinal value to non-volatile constituents. Removal of part of
solvent is permissible.
Liquid
1
Fatty
base
Soft
paste
Solution – 1. Incorporation of theobroma oil (max 10%)
2. Incorporation of beeswax (more than 10%)
3. Incorporation of high melting point synthetic
fatty base e.g. Massa Estranium C and
Whitepsol E75
For liquids of group 2 the method for semi-solids is suitable.
20% of aqueous or hydro-alcoholic liquid can be
mechanically emulsified in theobroma oil.
Liquids are concentrated by evaporation (if permissible) or a
larger size of suppository is used.
WHITE
SUPPOSITORIES
Suppositories containing no coloured ingredient.
Care is taken to ensure that the product is looking white and
not a dirty looking grey.
Mould, tile, spatula, mortar, sieve, and hands must be clean.
Porcelain dish is preferred over metal dish because their
smooth surface is easy to wash and their white colour displays
dirt clearly.
E.g. Aminophylline, Cinchona and morphine white
suppositories.
SUPPOSITORIES WITH A GLYCERO-GELATIN
BASE
Dispensed
as
Unmedicated
Glycerol suppositories BP
Medicated
BPC pessaries of crystal violet,
and lactic acid
Density of the base:
Glycero-gelatin base is 1.2 times denser than
theobroma oil so the mould should be calibrated with it.
PREPARATION
1. Lubricate the mould with liquid paraffin or arachis
oil; invert and cool.
2.Take glycerol in evaporating dish and keep it in
water bath and heat it to 100°C
3. Dissolve thermostable water soluble medicament
in 30 ml of water and heat it to boiling in evaporating
dish for few minutes and avoid excessive
evaporation
4. Add water to powder gelatin and stir gently to wet
the material. If gelatin sheets are used then trim off
the hard outer edges and cut into small pieces.
5. Add hot glycerol, restir and transfer to the boiling
water bath for 15 min or until solution is complete.
Make sure that the dish is low in water bath for maximum
heating.
Stir gently to avoid formation of air bubbles.
Heating may be done direct on bunsen burner instead on water
bath provided following precautions are taken.
1. The preparation is watched constantly.
2. The bunsen is used as little as possible and only to restore
the temp. to 100°C. Overheating may reduce the gelatin
strength .
3. The gelatin is not allowed to settled at the bottom of the
dish
4. If settled, gelatin may char or remain on the sides above the
liquid level where it may denature and insoluble.
In this method there is less risk of skin formation than the water
bath method.
6. When the solution is complete weigh the dish
and the contents
7. If necessary add or evaporate the purified water
to obtain the correct weight and remove the air
bubbles by passing it thorough muslin cloth
8. Pour the hot mass to the chilled moulds
9. Overfilling of the mould is not necessary
because glycero-gelatin bases contract very little
on cooling and also the excess cannot be
removed off neatly. So fill it to slight convexity
10. Leave the mould in an ice box or refrigerator
for about half an hour
12. Remove the mould and open it.
13. If there are signs of spliting of
suppositories from the centre line then
invert the mould and try to open it from
the bottom
14. Peel away each suppository from the
base to tip and stand it on its base on a
tile very thinly lubricated with liquid
paraffin or oil
15. If necessary trim off the base and
then roll each suppository to apply a coat
of lubricant to prevent its sticking to the
container.
16. Soluble thermolabile
medicaments are
dissolved in water or
specified solvent and this
solution is incorporated
in molten mass
17. Insoluble
substances are rubbed
down on a tile with part
of the glycerol and
melted base is not
used for this purpose it
is difficult to remelt the
base
GLYCERO-GELATIN AS PESSARY
BASE
Glycero-gelatin pessaries heated to about 100°C for 1 hour with
high concentration of glycerol (antibacterial agent) because
gelatin is obtained from natural source so may be contaminated
with pathogenic micro-organisms like E.Coli.
SUPPOSITORIES WITH A MACROGOL
BASE
Prepared in the same as that of synthetic
base with following changes
Mould must
not be
lubricated or
chilled –
rapid cooling
causes
brittleness
Do not
lubricate the
mould –
Lubrications
spoils the
surface
Medicaments
and base are
melted
together at
same
temperature;
mixed and
stirred to
form a stable
emulsion
Water soluble
ingredients
are dissolved
in water
before
addition
Insoluble
medicaments
are added
same to that
of synthetic
bases
Mass is
poured as
cool as
possible and
moulds are
over filled
II] 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
III] COMPRESSION MOLDING - 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
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
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)
PACKAGING AND LABELLING
FOR PESSARIES
Glass bottles Plastic bottles
Labelling :
1. Moisten the pessaries with water before insertion to
reduce stinging caused by osmotic withdrawl of water
to reduce the tissues during solution in vagina.
2. For vaginal use only or not to be taken orally.
3. Store in a cool place.
QUALITY CONTROL OF
SUPPOSITORIES
Appearance
Uniformity of weight
Disintegration

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Suppositories

  • 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 sometimes 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. 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.
  • 4. 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
  • 5. TYPES OF SUPPOSITORIES • Cone or torpedo shaped weighing 1 – 2 gRectal • 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 longNasal bougies • Pencil shapedEar cones
  • 6. SIZE OF SUPPOSITORIES 0 For Children 1,2 & 3 For rectal use 4 Pessaries A & B Nasal & urethral bougies
  • 8. RECTUM PHYSIOLOGY • Terminal 15-19 cm of large intestine (LI) • Rectal Fluids -> no buffering capacity • 1. 2 - 3 mL • pH 6.8 • Mild environment / drug can change pH • LI function absorb H2O and electrolytes • „Low surface area -> poor absorption compare SI
  • 9. RECTAL BLOOD CIRCULATION Main blood supply superior rectal artery Blood return 3 blood veins – Superior hemorrhoidal vein – Middle hemorrhoidal vein – Inferior hemorrhoidal vein
  • 10. Superior hemorrhoidal vein Inferior mesenteric -> Hepatic portal -> Liver Middle and inferior Drug goes directly into systemic circulation No first pass metabolism by liver Drug avoids stomach and digestive enzymes Patient counseling -> don't place too high in rectum
  • 13. PROBLEMS IN FORMULATION OF SUPPOSITORIES 1. Water in suppositories Formulators do not like to use water for dissolving drugs in suppositories for the following reasons : a. Water causes oxidation of fats. b. If the suppositories are manufactured at a high temperature, the water evaporates, the drugs crystallize out. c. Absorption of water soluble drugs is enhanced only if the base is an oil – in – water emulsion with more than 50% of the water in the external phase. d. Drug excipient interactions are more likely to happen in the presence of water. e. Bacterial contamination may be a problem, so we may be forced to add a preservative.
  • 14. 2. Hygroscopicity Glycerogelatin suppositories lose moisture in dry climates and absorb moisture in humid conditions The hygroscopicity of polyethylene glycol bases depends on the chain length of the molecule As the molecular weight of these ethylene oxide polymers increases the hygroscopicity decreases
  • 15. 3. Drug-excipient interactions Incompatibilities exist between polyethylene glycol base and some drugs. Sodium barbital and salicylic acid crystallize out of polyethylene glycol. High concentrations of salicylic acid soften polyethylene glycol to an ointment like consistency. Penicillin G is stable in cocoa butter and other fatty bases. It decomposes in polyethylene glycol bases.
  • 16. 4. Viscosity When the base has low viscosity, sedimentation of the drug is a problem. 2% aluminium monostearate may be added to increase the viscosity of the base Cetyl and stearyl alcohols or stearic acid are added to improve the consistency of suppositories
  • 17. 5. Brittleness Cocoa butter suppositories are elastic, not brittle Synthetic fat bases are brittle This problem can be overcome by keeping the temperature difference between the melted base and the mold as small as possible Materials that impart plasticity to a fat and make them less brittle are small amounts of Tween 80, castor oil, glycerin or propylene glycol
  • 18. 6. Density Density of the base, the drug, the volume of the mould and whether the base is having the property of volume contraction are all important. They all determine the weight of the suppository 7. Lubrication of moulds Some widely used lubricating agents are mineral oil, aqueous solution of SLS, alcohol and tincture of green soap. These are applied by wiping, brushing or spraying
  • 19. 8. Volume contraction On solidification the volume of the suppository decreases. The mass of the suppository pulls away from the sides of the mould. This contraction helps the suppository to easily slip away from the mould, preventing the need for a lubricating agent. Sometimes when the suppository mass is contracting, a hole forms at the open end. This gives an inelegant appearance to the suppository. Weight variation among suppositories is also likely to occur. This contraction can be minimized by pouring the suppository mass slightly above its congealing temperature into a mould warmed to about the same temperature. Another way to overcome this problem is to overfill the molds, and scrape off the excess mass which contains the contraction hole.
  • 20. 9. Displacement value The volume of suppositories from a particular mould will be constant but the weight will vary because the densities of the medicaments usually differ from the density of the base, and hence the density of the medicament will affect the amount of the base required for each suppository
  • 21. 10. Weight and volume control Various factors influence the weight of the suppository, the volume of the suppository and the amount of active ingredient in each suppository. They are: 1. Concentration of the drug in the mass 2. Volume of the mould cavity 3. The specific gravity of the base 4. Volume variation between moulds 5. Weight variation between suppositories due to the inconsistencies in the manufacturing process. The limit for the weight variation in suppositories is 5%.
  • 22. 11. Rancidity The unsaturated fatty acids in the suppository bases undergo auto oxidation and decompose into aldehydes, ketones and acids. These products have strong, unpleasant odours The lower the content of unsaturated fatty acids in a base, the higher is its resistance to rancidity
  • 23. DRUG 1. Should have sufficient absorption from particular body cavity (if for systemic use) 2. Best suited for drugs undergoing first pass metabolism, degrade in GI fluids or irritate the GI mucosa 3. Should be easily dispersible or soluble in the base 4. Should be soluble to achieve homogeneity but should not have more affinity for the base or else it wouldn't get released 5. Particle size should be less to improve bioavailability and decrease irritation 6. Density and solubility of the drug should ensure minimum usage of base and formation of smaller suppositories 7. Drug should be compatible and stable in base and at processing conditions
  • 24. 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
  • 25. TYPES OF SUPPOSITORIES BASES Suppository bases Fatty bases Cocoa Butter Synthetic fats Proprietary synthetic bases Water soluble or water miscible bases Glycero- gelatin Macrogols
  • 27. COCOABUTTER (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 oleopalmitostearin and oleodistearin 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 – innocuous, bland, and non-reactive, and melts at body temp.
  • 28. Disadvantages Polymorphism Adherence to mould Low softening point Melting point reduction Deterioration during storage Poor water absorbing capacity Leakage from the body
  • 29. 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.
  • 30. 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.
  • 31. 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
  • 32. 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.
  • 33. 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
  • 34. 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.
  • 35. 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.
  • 36. 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.
  • 37. 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.
  • 38. PROPRIETARY SYNTHETIC BASES Whitepsol (formerly called Imhausen) • 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 with chain lengths of C11 to C17. Grade B is recommended for general dispensing. Massuppol • This differs from the previous materials in being single general purpose base with only one modification, for cold moulding. • 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.
  • 40. 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.
  • 41. 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. Gelatin is incompatible with protein precipitants such as tannic acid.
  • 42. 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.
  • 43. 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.
  • 44. 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.
  • 45. 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.
  • 46. 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.
  • 48. 3 METHODS 1. Moulding 2. Hand rolling 3. Compression
  • 50. CLEANING OF MOULDS Mould Interior – Don’t scrap or rub with abrasive Immerse in hot detergent water Wipe with soft cloth Rinse thoroughly
  • 51. NORMAL CAPACITIES OF MOULDS 1g (15gr) 2 g (30gr) 4 g (60gr) 8 g (120gr)
  • 52. WAYS OF PREPARING PROPRIETARY SUPPOSITORIES – CONVENTIONAL MOULDS Individual packing in laminated foil Strip packing in hermatically sealed tight fitting laminated foil or plastic film
  • 53. 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.
  • 54. 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.
  • 55. 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.
  • 56. 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
  • 57. 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
  • 58. Industry – silicone fluid is used as lubricant. Incompatibility between lubricant, medicament and adjuncts should be checked. Lubricant should be applied on pad of guaze or muslin or with a small fairly stiff brush. Cotton wool is unsuitable because fibres 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.
  • 59. GENERAL METHODS OF PREPARATION Suppositories Fatty base Insoluble solids Solids soluble in the base Semi-solids Liquids White suppositories Glycero- gelatin base Macrogol base
  • 60. 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.
  • 61. 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
  • 62. 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
  • 63. 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
  • 64. 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
  • 65. 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.
  • 66. 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.
  • 67. SUPPOSITORIES CONTAINING SOLIDS SOLUBLE IN BASE When soluble substances are used there is depression in melting point. Product is satisfactory and quite firm. Occasionally the suppositories become too soft to use. To avoid this a synthetic base with higher melting should be used. E.g Massa Estranium Type C or Witepsol E75 BPC – White beeswax (M.P: 62 to 64 °C) – complicates the preparation when used with theobroma oil – affects the solidifying point of the base and delays setting. These problems can be avoided if following procedure is followed
  • 68. 1. Melt the base 2. Cool it to consisten cy of thick cream 3. Add finely powdered solid 4. Stir until fully dissolved 5. Proceed in usual way
  • 69. SUPPOSITORIES CONTAINING SEMI- SOLIDS 1. Reduce the viscosity of drug by trituration on warm tile with enough water 2. Homogenous liquid of consistency of glycerol or somewhat thinner is formed 3. Added water is allowed for and transfer the dilution to the tared container 4. Add sufficient melted base to produce a weight equal to the product of the nominal capacity of the mould and the number of suppositories in excess 5. Mass is stirred vigorously to form a mechanical emulsion and the preparation is completed in normal manner
  • 70. Care should be taken during stirring the mass to form mechanical emulsion because it should not be continued before the liquid becomes somewhat unpourable. Satisfactory dispersion can be ensured by – • The mixture must stirred vigorously to produce a perfect dispersion. • Pouring must be delayed to the last possible moment so that the globules of aqueous liquid are enclosed in a solid film fat. In this method synthetic bases are preferred because they contain emulsifying agents. Water containing suppositories are susceptible to microbial growth so addition of preservative agent is necessary. Water may evaporate leaving cavities or creating high local concentration of drug that cause irritation. Failure to establish and maintain a stable emulsion during preparation may lead to moisture seeping of the product.
  • 71. SUPPOSITORIES CONTAINING LIQUIDS Liquids used in suppositories fall into 2 categories 1. Liquids that are volatile (e.g. volatile oils) or owe their medicinal use to volatile constituents (e.g. peru balsam). These cannot be evaporated. They lower the melting point of fatty base. 2. Liquids that are aqueous or hydro-alcoholic that owe their medicinal value to non-volatile constituents. Removal of part of solvent is permissible.
  • 72. Liquid 1 Fatty base Soft paste Solution – 1. Incorporation of theobroma oil (max 10%) 2. Incorporation of beeswax (more than 10%) 3. Incorporation of high melting point synthetic fatty base e.g. Massa Estranium C and Whitepsol E75
  • 73. For liquids of group 2 the method for semi-solids is suitable. 20% of aqueous or hydro-alcoholic liquid can be mechanically emulsified in theobroma oil. Liquids are concentrated by evaporation (if permissible) or a larger size of suppository is used.
  • 74. WHITE SUPPOSITORIES Suppositories containing no coloured ingredient. Care is taken to ensure that the product is looking white and not a dirty looking grey. Mould, tile, spatula, mortar, sieve, and hands must be clean. Porcelain dish is preferred over metal dish because their smooth surface is easy to wash and their white colour displays dirt clearly. E.g. Aminophylline, Cinchona and morphine white suppositories.
  • 75. SUPPOSITORIES WITH A GLYCERO-GELATIN BASE Dispensed as Unmedicated Glycerol suppositories BP Medicated BPC pessaries of crystal violet, and lactic acid Density of the base: Glycero-gelatin base is 1.2 times denser than theobroma oil so the mould should be calibrated with it.
  • 76. PREPARATION 1. Lubricate the mould with liquid paraffin or arachis oil; invert and cool. 2.Take glycerol in evaporating dish and keep it in water bath and heat it to 100°C 3. Dissolve thermostable water soluble medicament in 30 ml of water and heat it to boiling in evaporating dish for few minutes and avoid excessive evaporation 4. Add water to powder gelatin and stir gently to wet the material. If gelatin sheets are used then trim off the hard outer edges and cut into small pieces. 5. Add hot glycerol, restir and transfer to the boiling water bath for 15 min or until solution is complete.
  • 77. Make sure that the dish is low in water bath for maximum heating. Stir gently to avoid formation of air bubbles. Heating may be done direct on bunsen burner instead on water bath provided following precautions are taken. 1. The preparation is watched constantly. 2. The bunsen is used as little as possible and only to restore the temp. to 100°C. Overheating may reduce the gelatin strength . 3. The gelatin is not allowed to settled at the bottom of the dish 4. If settled, gelatin may char or remain on the sides above the liquid level where it may denature and insoluble. In this method there is less risk of skin formation than the water bath method.
  • 78. 6. When the solution is complete weigh the dish and the contents 7. If necessary add or evaporate the purified water to obtain the correct weight and remove the air bubbles by passing it thorough muslin cloth 8. Pour the hot mass to the chilled moulds 9. Overfilling of the mould is not necessary because glycero-gelatin bases contract very little on cooling and also the excess cannot be removed off neatly. So fill it to slight convexity 10. Leave the mould in an ice box or refrigerator for about half an hour
  • 79. 12. Remove the mould and open it. 13. If there are signs of spliting of suppositories from the centre line then invert the mould and try to open it from the bottom 14. Peel away each suppository from the base to tip and stand it on its base on a tile very thinly lubricated with liquid paraffin or oil 15. If necessary trim off the base and then roll each suppository to apply a coat of lubricant to prevent its sticking to the container.
  • 80. 16. Soluble thermolabile medicaments are dissolved in water or specified solvent and this solution is incorporated in molten mass 17. Insoluble substances are rubbed down on a tile with part of the glycerol and melted base is not used for this purpose it is difficult to remelt the base
  • 81. GLYCERO-GELATIN AS PESSARY BASE Glycero-gelatin pessaries heated to about 100°C for 1 hour with high concentration of glycerol (antibacterial agent) because gelatin is obtained from natural source so may be contaminated with pathogenic micro-organisms like E.Coli.
  • 82. SUPPOSITORIES WITH A MACROGOL BASE Prepared in the same as that of synthetic base with following changes Mould must not be lubricated or chilled – rapid cooling causes brittleness Do not lubricate the mould – Lubrications spoils the surface Medicaments and base are melted together at same temperature; mixed and stirred to form a stable emulsion Water soluble ingredients are dissolved in water before addition Insoluble medicaments are added same to that of synthetic bases Mass is poured as cool as possible and moulds are over filled
  • 83. II] 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
  • 84. III] COMPRESSION MOLDING - 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
  • 85. 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
  • 86. 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)
  • 87. PACKAGING AND LABELLING FOR PESSARIES Glass bottles Plastic bottles Labelling : 1. Moisten the pessaries with water before insertion to reduce stinging caused by osmotic withdrawl of water to reduce the tissues during solution in vagina. 2. For vaginal use only or not to be taken orally. 3. Store in a cool place.