Suppositories SB 2020

Suppositories
Presented by-
Prof. Mirza Salman Baig
Assistant Professor in Pharmaceutics

Suppositories
A suppository is a medicated solid dosage form generally
intended for use in body cavities like 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 made to disintegrate in body fluids.

Suppositories
• The medicament is incorporated into a base such as
• Cocoa butter which melts at body temperature,
• Glycerinated gelatin or PEG which slowly dissolves in the
mucous secretions.
• Suppositories used for producing-
• Local action,
• Systemic effect or
• To exert a mechanical effect to facilitate emptying the
intestine.
3

Types of suppositories
• Rectal suppositories: These are the preparations meant for introduction into the rectum for their
local or systemic effect. They are tapered at one or both ends and usually weigh about 2 g. The
rectal suppositories meant for children are smaller in size with a weight of 1 g.
• Vaginal suppositories (Pessaries): They are semisolid bodies meant for introduction into vagina.
They are larger than rectal suppositories and vary in weight from 3 g to 6 g or more. They may be
conical, rod shaped, or wedge shaped and are exclusively used for their local action.
• Urethral suppositories (Urethral bougies): They are meant for introduction into the urethra.
They weigh between 2 g and 4 g with length 2–5 inch. They are very rarely used and should be
sterile.
• Nasal suppositories (Nasal bougies): They are meant for introduction into nasal cavity. They are
similar in shape to urethral bougies and are prepared with glycero-gelatin base.
• Ear cones (Aurinaria): They are miniature bodies meant for introduction into the ear. Theobroma
oil is used as a base; these are prepared in a urethral bougies mold and cut according to the
required size.

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

ADVANTANGES OF SUPPOSITORY
• It is the alternated dosage form for drugs which have less
bioavailability when it is taken orally.
• Drugs having bad odor and taste can be used in suppository form.
• It is suitable for the drugs which are metabolized by portal
circulation (first pass effect)
• It is suitable for drugs which produce irritating effect in GIT.
• It is suitable for unconscious patients which can not taken drugs
orally.
• It is suitable for infants and old people who find difficulty in
swallowing of drugs.

DISADVANTAGE OF SUPPOSITORY
• The manufacturing process is more difficult as compare other
formulation.
• The drugs which cause irritation to mucous membrane can not
be administrated by this form.
• The most important problem is storage condition because it
stored at low temp. (10-20 0C ), otherwise the bases get
liquefied.
• Leakage problem is also most critical problem along with
suppository after introducing in body cavity at elevated
temperature.
• Incomplete absorption

Desirable features of suppositories
• Stable at room temperature
• Melt at body temperature
• Disintegrate at site of administration
• Release maximum drug

•The patient is unable to use the oral route (inflection of
GIT, nausea, unconsciousness, post-operation, young, old
and mentally disturbed patients).
•The drug is less suited for oral route (causes GI side
effects, insufficiently stable at pH of GIT, susceptible to
enzymatic degradation, has first- pass effect, with
unacceptable taste)
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• Slow and incomplete absorption.
• Inter and intra-subject variation.
• Problems with large scale production of suppositories
• Short shelf life.
• Demanding stringent storage conditions.
10

•Local effect:
- In case of pain, itching and haemorroids
- locally active drugs include astringents, antiseptics, local
anaesthetics, vasoconstrictors, anti-inflammatory
compounds, soothing and protective agents and laxatives.
•Systemic effect:
- Anti-asthmatics, anti-rheumatics and analgesics.
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Anatomy and physiology of rectum

Anatomy and physiology of rectum
•Anatomically the rectum is part
of the colon
•The rectum is about 15 to 20
cm long.
•It is a hollow organ with a
relatively flat wall surface,
•It dose not have villi
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• The anus is controlled by an internal sphincter of smooth
muscle and an external sphincter of skeletal muscle.
• Under normal conditions, the rectum is empty, and filling
provokes a defecation reflex which under voluntary control.
• Rectum contains (about 2 to 3 ml) mucous, which has a pH
of 7.4 and little buffering capacity.
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• The rectal tissues are
drained by the inferior,
middle and superior
haemorrhoidal veins,
• Only the superior vein
connects with the
hepatic-portal system.
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• Medicaments absorbed in the lower part of the rectum are
delivered directly into the systemic circulation, thus avoiding the
first-pass metabolism.
• However, it has been found that suppositories can settle high
enough in the rectum to allow at least some drug absorption into
the superior vein.
• Thus keeping the drug in the lower part of the rectum would be
advisable.
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• Insertion of a suppository into the rectum results leads to the
bioavailability of the drug.
• Suppository will either dissolve in the rectal fluid or melt on the
mucous layer.
• Since the volume of rectal fluid is so small, complete dissolution of
the base require extra water.
• Drugs in the suppository diffuse out & absorption will be passive
diffusion
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Factors affecting drug absorption from rectal
suppositories
Physiological Factors
Physiochemical characteristic of drug
Physiochemical characteristic of base and adjuvants

i. Properties of rectal mucus
ii. Quantity of fluid available
iii. Contents of the rectum
iv. Motility of the rectal wall

• The properties of the rectal fluid, such as composition, viscosity, pH
and surface tension also play role in rectal absorption
• pH of rectum play significant in controlling rate of drug absorption
from mucosa
• Schanker reported, rectal has no buffer capacity hence dissolving
drug determine the pH in ano-rectal region
• Schanker reported, weak acid and bases are more rapidly absorbed
than strong one (unionized absorb fast)
• Change in pH could increase the proportion of unionized form of
drug and hence increase absorption. Absorption of acidic drug
increase in acidic environment
• No esterase In the rectum or peptidase activity is present, resulting
in a much greater stability of peptide-like drugs

• The quantity of fluid available for drug dissolution is very small
(approximately 3 mL). Thus the dissolution of slightly soluble
substances drug (for example phenytoin)remain to be the slowest
step in the absorptive process. Riegelman and crowall showed that
rate limiting step is the diffusion of drug at the site of absorption.
Diffusion affected by amount of fluid present in colon
• Contents of the rectum: The rectum is usually empty, except
temporarily when faecal matter arrives from higher parts of the
colon.
• Motility of the rectal wall: The rectal wall may exert a pressure on a
suppository because of peristaltic waves of contractions which
originate from the colonic motor complexes

i. Lipid-water solubility of the drug
ii. Particle size of the drug
iii. Degree of drug ionization
iv. Nature of the base

• The lipid water partition coefficient of the drug is an important
consideration in the selection of the suppository base and in anticipating
drug release from that base. A drug with a high partition coefficient is
likely to be absorbed more readily from a water soluble bases.
• 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 a hydrophilic drug in its saturation concentrations.
• Water-soluble bases dissolve in rectal fluids and release both water-
soluble and oil-soluble drugs.

• Particle size of the drug
• For drugs present in the suppository in the un-dissolved form, the
smaller the size, the more readily the dissolution of the particle and
the greater the chance for rapid absorption.
• The smaller the particles the less the possible mechanical irritation to
the patient (esp. < 50 micron) and the higher the dissolution rate

• Degree of drug ionization
• Absorption through rectal mucosa proceeds in accordance with pH-
partition theory.
• At the slightly alkaline pH of rectal mucosa, weakly basic drugs will
exist in unionized lipid– soluble form, hence readily absorbed.

• Nature of the base
• If the base interacts with the drug inhibiting its release, drug
absorption will be impaired or even prevented.
• 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 thorough drug release and absorption.

• 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:
• Oleaginous (fatty) bases
Ex. Cocabutter (Theobroma)
• Water soluble or miscible bases
Ex. Glycero-Gelatin base /PEG

(Fatty vehicles)
• The fatty vehicles in use nowadays are almost exclusively semi- or fully synthetic
ones.
• Cocoa butter is no longer used because of its many disadvantages, such as its well
known polymorphic behavior, its insufficient contraction at cooling, low softening
point, chemical instability
• The semisynthetic type of fatty vehicles (sometimes termed adeps solidus) have
few or none of the problems mentioned above. The general composition of both
types is mixed triglycerides with C12-C18 acids.
• In the semisynthetic vehicles these acids are saturated, whereas cocoa butter
contains a considerable amount of the unsaturated oleic acid (see iodine number
in the table, which for reducing drugs should be <0.5).

(Fatty vehicles)
• The presence of oleic acid is almost solely responsible for the special properties
of this vehicle.
• The melting range of the (semi) synthetic bases is usually approximately 3°C
higher than that of cocoa butter; the acid content is lower (mostly <0.5), which
is one of the reasons that the ageing of aminophylline suppositories is slower
when (semi) synthetic vehicles are used.
• The hydroxyl number in the table refers directly to the amount of mono- and
diglycerides present in the fatty base. A high number means that the power to
absorb water is high. This may lead to an increased rate of decomposition for
drugs that are easily hydrolysed, It could also lead to the formation of a w/o
emulsion in the rectum, which is very low drug release rate. An advantage of a
high hydroxyl number is the larger melting and solidifying range

(Water-soluble vehicles)
• Water-soluble (or miscible) vehicles are much less used, for reasons to be
discussed below. They comprise the classic glycerol-gelatin or soap bases,
which are used exclusively for laxative purposes or in vaginal therapy.
• The macrogols are also used, which consist of mixtures of polyethylene
glycols of different molecular weight. The melting point is well over body
temperature, which means that they mix with the rectal fluid.
• For true dissolution, the available volume of rectal fluid (1-3 mL) is too
small. Because of their high melting point they are especially suited for
application in tropical climates,
• The incorporation of at least 20% water and moistening before insertion
can help to reduce this problem.

(Special bases)
• In emulsion type of bases, amount of water-soluble drug release
increase with increase in water content of the base.
• Salicylates found to improve rectal absorption of antibiotic from
lipophilic bases

Suppository bases: specifications

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)
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2- Melting range
❖Since fats 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.
❖Softening point.
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3- Solidi Fat Index (SFI)
❖Graph is plotted between %solid
vs temperature
❖Base with sharp drop of curve is
brittle.
❖This require reduced
temperature differential between
mould and base.
❖SFI is determined by
dilatometry.

4- Hydroxyl value
❖This value give quantity of momo and diglycerides present in
oleogeneous base.
❖Milligram of KOH required to nutralize unreacted acetic acid.
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5- 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 10ºC or more, the time required for solidification
may have to be shortened for a more efficient
manufacturing procedure by augmenting (increasing)
refrigeration.
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6- Saponification value
❖The number of milligrams of potassium hydroxide required
to neutralize the free fatty 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.
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7- 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.
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8- 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.
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9- Acid value
❖The number of milligrams of KOH 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.
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Desired features and
classification
of suppository bases

Desired features /
Ideal Suppository Base

The ideal suppository base should be
• Nontoxic and nonirritating to sensitive and inflamed tissues.
• Non sensitizing (allergic)
• Inert and compatible with a broad variety of medicaments.
• Can be easily manufactured by compression or molding.
• It has no meta-stable forms.
• Dissolve or disintegrate in the presence of mucous secretions or melt at
body temperature ( 360 C) to allow for the release of the medication.
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Desired features /

Desired features /
• Remain molten for a sufficient period to allow pouring into molds.
• Solidify sufficiently rapidly to minimize sedimentation of dispersed
solids.
• Shrink on cooling to allow easy withdrawal of the suppository from the
mold.
• Has wetting and emulsifying properties.
• High water number (so that more water could be incorporated)
• Stable on storage, does not change color, odor and drug release pattern.

Desired features /
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.
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Control parameters of suppositories
• Appearance
• Weight
• Disintegration
• Melting (dissolution) behaviour
• Mechanical strength
• Content of active ingredient
• Release

Classification
of suppository
bases
• Oleaginous (fatty) base: Cocabutter
(Theobroma)
• Water soluble or miscible bases:
Glycero-Gelatin base/PEG
• Miscellaneous bases

1. Oleaginous (fatty) base:
• Coca butter (Theobroma)
• Substitutes of Coca butter (Theobroma)
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• Theobroma Oil or cocoa butter is used as a suppository base because, in
large measure, it fulfills most of the requirements of an ideal suppository
base.
• Cocoa butter is primarily a tri-glyceride (Oleopal mitostearin) , it is
yellowish- white, solid, brittle fat, which smells and tastes like chocolate.
• At ordinary room temperatures of 15° to 25°C it is a hard, amorphous solid,
• It melt at 30° to 35°C i.e., at body temperature, it melts to a bland,
nonirritating oil.
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Theobroma/Coca 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.
52

• Shrinks only slightly on solidification; a mold lubricant is therefore
required.
• Exists in four polymorphic forms with different melting points
• Alfa 24 °C
• Beta' 28-31 °C
• Beta (stable) 34-35 °C (beta' slowly changes to beta stable)
• Gamma 18 °C
• Theobroma should only be heated for a short time and at temperatures
just below 36 °C in order to minimize the formation of the unstable low
melting point forms.
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Disadvantages

• 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 climates.
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How formation of unstable form of polymorphs
can be avoided?
• If mass is not completely melted, remaining crystal prevent formation of
unstable crystal.
• Seeding
• Solidified mass is tempered at 28-32 °C to convert Beta'--> Beta
Stable.
• Prolonged heating and overheating must be avoided.

Effect of Additives
• Wax/Spermaceti added to keep melting point at 35 °C when drug used is volatile
which can reduce melting point.
• Emulsifier to increase water holding capacity.
• 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 remedy 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 interaction or affect the release of drug from suppository.

Substitutes of Theobroma
• Synthetic triglycerides
• Palm kernel oil
• Hydrogenated corn oil

Synthetic triglycerides (Hard fat)
• The newer synthetic tri-glycerides consist of esterified, hydrogenated
or fractionated vegetable oils.
• Hard fat is a mixture of mono, di and tri-glycerides of saturated fatty
acids (C10 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.
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• A tendency to fracture upon pouring into chilled molds 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.
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Advantages over cocoa butter
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).
3. The melting range of the synthetic bases is usually about 3ºC higher than that of
cocoa butter
4. The acid content is lower (mostly <0.5)
5. The solidification temperatures of hard fats are unaffected by over heating.
6. There is only a small temperature difference between melting and solidification,
thus the sedimentation of suspended drugs is minimized.
7. The water absorbing capacity of hard fats can be improved (to about 25% or
30% w/w) by inclusion of glyceryl monostearate.

• Glycerinated gelatin
• Polyethylene glycol (PEG) polymers.
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2. Hydrophilic suppositories base

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 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.
62

• 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 draw water from
mucous.
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• 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.
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Preparation

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

Polyethylene Glycol Polymers
• Polyethylene Glycol Polymers 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.
66

• 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
• Some times more molecular weights PEG mixed in various
proportions as needed to yield a finished product of satisfactory
hardness and dissolution time.
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• 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 melting points.
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• 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.
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1450
8000
300
8000
30%
70%
60%
40%
300
6000
1000
3350
1000
3350
48%
52%
95%
5%
75%
25%
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• 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).
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Suppositories can be extemporaneously prepared by one of three
methods.
1. Hand Rolling
2. Compression molding
3. Fusion Molding
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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
(pulverized) cocoa butter and active ingredients in a mortar.
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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.
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• 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 consistency.
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• On large scale, mechanically operated mixers and a warmed
mixing vessels are used.
• 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.
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2. Compression molding (machine)
• Prepared mass C is placed in a cylinder A
• It is forced through narrow opening D by means
of piston B into a mold.
• Threads of mass pass in the mold G and are
compressed until a homogenous fused mass is
formed in E.
• The mass and compression cylinder of the
machine may be chilled to prevent heat of
compression from making the mass too fluid.
• When the die is filled with the mass, a movable
end 'plate-F' at the back of the die is removed
• Additional pressure is applied to eject suppository

3. Fusion Molding
1. Melting the suppository base
2. Dispersing/emulsifying or
dissolving the drug in the
molten 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.
78

• 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.
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• 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 rarely necessary when the suppository base is contracting
sufficiently on cooling.
• Lubrication is usually necessary when glycerinated gelatin suppositories
are prepared.
80

Automatic moulding machine
• it can make 6000 unit/hr

Formulation concideration
• For local use / Systematic use?
• Site of application, rectal/vaginal/urethral?
• Quick release/ prolonged release?

Properties of suppositories for systemic effect
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.
7.Drug should be compatible and stable in base and at processing
conditions
8.Water soluble drug added in oil soluble base and vice versa

Properties of Suppositories for local effect
1. Nonabsorbable drug
2. Nonabsorbable base
3. Slow melting base
4. Should melt within 4-6 hour

Problems in formulation of suppositories
1. Water in Suppositories
2. Hygroscopicity
3. Incompatibilities
4. Viscosity
5. Brittleness
6. Density
7. Volume contraction
8. Lubrication
9. Dose displacement
10.Wt. and volume control
11.Rancidity/antioxidant

1. Water in suppositories
Formulators do not like to use water for dissolving drugs in suppositories
for the following reasons :
a) Water causes hydrolysis 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
d) And more than 50% of the water should be in the external phase.
e) Drug excipient interactions are more likely to happen in the presence
of water.
f) Bacterial contamination may be a problem, so we may be forced to
add a preservative.

2. Hygroscopicity
a) Glycerogelatin suppositories lose moisture in dry climates and
absorb moisture in humid conditions
b) The hygroscopicity of polyethylene glycol bases depends on
the chain length of the molecule
c) As the molecular weight of these ethylene oxide polymers
increases the hygroscopicity decreases

3. Drug-excipient interactions
a) Incompatibilities exist between polyethylene glycol base and some
drugs eg. quinine.
b) Sodium barbital and salicylic acid crystallize out of polyethylene
glycol.
c) High concentrations of salicylic acid soften polyethylene glycol to an
ointment like consistency.
d) Penicillin G is stable in cocoa butter and other fatty bases but
decomposes in polyethylene glycol bases.

4. Viscosity
a) When the base has low viscosity, sedimentation of the drug
before solidification is a problem.
b) Well mixed mass should be handled at lowest possible
temperature.
c) 2% aluminum monostearate may be added to increase the
viscosity of the base
d) Cetyl and stearyl alcohols or stearic acid are added to improve the
consistency of suppositories

5. Brittleness
a) Cocoa butter suppositories are elastic, not brittle
b) Synthetic fat bases are brittle
c) This problem can be overcome by keeping the temperature
difference between the melted base and the mold as small as
possible
d) 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
a) Density of the base, the drug, the volume of the mold and whether
the base is having the property of volume contraction are all
important.
b) They all determine the weight of the suppository

7. Volume contraction
a) Because of volume contraction suppository easily slip away from
the mold, preventing the need for a lubricating agent.
b) 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.
c) To avoid this problem of volume contraction
d) Overfill the molds, and scrape off the excess mass which contains
the contraction hole
e) Pour the suppository mass slightly above its congealing temperature
into a mould warmed to about the same temperature.

8. Displacement value
The displacement value is defined as the number of gram of
ingredients (or Drug) that displace one gram of Suppository base
The volume of suppositories from a particular mold 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

Displacement value (Example 1)
If a prescription requires 400 mg of bismuth subgallate per suppository weighing two
grams, what would be the displacement value if it is known that six suppositories with
required bismuth subgallate weigh 13.6 g?
Theoretical weight of six cocoa butter suppositories without bismuth subgallate = 12 g
Given weight of six cocoa butter suppositories with bismuth subgallate =13.6 g
Wt. of bismuth subgallate in the six suppositories = 0.4 × 6 = 2.4 g
Wt. of cocoa butter in the bismuth subgallate suppositories = 13.6 − 2.4 = 11.2 g
Cocoa butter displaced by 2.4 g of bismuth subgallate = 12 − 11.2 = 0.8
The displacement value of bismuth subgallate is 2.4/0.8 = 3

Example 2
• If 12 cocoa butter suppositories containing 40% zinc oxide weigh 17.6 grams, what
is the displacement value of zinc oxide? Assume that the suppositories are made
in a 1-g mold
• Given weight of 12 suppositories with zinc oxide = 17.6 grams
• Weight of zinc oxide in the suppositories = (40/100) × 17.6 = 7.04 g
• Weight of cocoa butter in the suppositories = (60/100) × 17.6 = 10.56 g
• Theoretical weight of 12 suppositories without zinc oxide = 12 g
• Cocoa butter displaced by 7.04 g of zinc oxide = 12 − 10.56 = 1.44
• Displacement value of zinc oxide = (7.04/1.44) = 4.89

9. 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 are--
a) Concentration of the drug in the mass
b) Volume of the mold cavity
c) The specific gravity of the base
d) Volume variation between molds
e) Weight variation between suppositories due to the inconsistencies in the
manufacturing process,
f) The limit for the weight variation in suppositories is 5%.

10. Lubrication of molds
a) Some widely used lubricating agents are mineral oil, aqueous
solution of SLS, alcohol and tincture of green soap.
b) These are applied by wiping, brushing or spraying

11. Rancidity
a) The unsaturated fatty acids in the suppository bases
undergo autooxidation and decompose into
aldehydes, ketones and acids. These products have
strong, unpleasant odours
b) The lower the content of unsaturated fatty acids in a
base, the higher is its resistance to rancidity

Evaluation of suppositories
Finished suppositories are routinely inspected for; appearance &
content uniformity beside this--
• Melting range test/micromelting range
• Softening time (U tube water bath & glass rod)
• Drug release test
• Breaking test (Fragility test)
• Disintegration/Dissolution test

• Macro-melting range is a measure of the
time it takes for the entire suppository to
melt when immersed in a constant-
temperature (37ºC) water bath. USP tablet
disintegration apparatus is used
• Micromelting range for fat base using
capillary tubes
Open capillary apparatus for melting point

Softening time
• In this test a U tube is partially immersed
in a constant temperature bath and is
maintained at a temperature between
35 to 37°C.
• There is a constriction in the tube in
which the suppository is kept
• and above the suppository, a glass rod is
kept.
• The time taken for the glass rod to go
through the suppository and reach the
constriction is known as or softening
time.
U tube
apparatus

Softening time
• Another apparatus is there for finding
“softening time” which mimics in vivo
conditions.
• It uses a cellophane tube, and the
temperature is maintained by water
circulation. Time taken for the suppository to
melt is noted

Breaking test
• To measure the fragility or brittleness
of suppository
• Double wall chamber in which the
test suppository is placed.
• Water at 37ºC 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.
10
3

• 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
• Different shape suppositories
have different value of
hardness.
10
4
Breaking test

Dissolution/Disintegration test
• In-vitro drug release pattern is measured by using ERWEKA®
Disintegration apparatus
• Aliquots of the release medium were taken at different time
intervals within the melting period.
• The drug content in the aliquots was determined using UV
• The drug release pattern was plotted (time versus-drug
release curve)

Packaging
• Aluminium foil
• Paper wrap
• in-package moulding

Packaging of suppositories
• They should not touch each other, otherwise they may
fuse together
• Proper wrapping with aluminum foil, or paper is required
• Machine packaging avoid nonuniformity
• after solidification wrapping
• sealing using two halves of plastic
• In package molding
• Top of package mold remain open, after mass injected it is
sealed
• High production rate
• At high temperature shape is retained

Packaging, labelling & Storage for suppositories
Rigid paperboard
boxes
Flat box with a lid
Labelling :
1. Store in a cool place
2. For rectal use only
3. Moisten before use (for glycero-gelatin and macrogol
bases)

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Suppositories SB 2020

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Suppositories SB 2020