2. Suppositories 2014.pdf

Suppositories
Integrated Physical Pharmacy and
Pharmaceutics II (Phar 3121)
Debre Berhan University
Health Science College
Pharmacy Department
Pharmaceutics Unit
Aychew M. (B.Pharm, MSc Candidate)
2014E.C

Chapter objectives
After completion of this chapter, the student will be
able to:
➢Compare and contrast various suppositories dosage
forms in terms of physical appearance, size, and
shape.
➢Describe the advantages and disadvantages of
suppository drug delivery
2
BY: Aychew M. IPP II(PHAR (3121) 2014EC

Chapter objectives…
➢Compare and contrast the various classes of
suppository bases.
➢Describe methods of suppository preparation.
➢Generate a listing of key counseling points a
pharmacist should share with the patient prescribed a
drug in a suppository drug delivery system.
3

Introduction
➢Suppositories are solid dosage forms intended for
insertion into body orifices where they melt, soften,
or dissolve and exert local or systemic effects
➢The derivation of the word suppository is from the
Latin supponere, meaning “to place under,” as
derived from sub (under) and ponere (to place)
4

Introduction…
➢The medicament is incorporated into a base that
melts at body temperature, or into one which slowly
dissolves in the mucous secretions
➢Suppositories are commonly used rectally and
vaginally and occasionally urethrally
5

Introduction…
➢The shape and size of a suppository must be such
that
✓ It can be easily inserted into the intended orifice
without causing undue distension, and
✓ Once inserted, it must be retained for the
appropriate period.
6

Introduction…
➢Rectal suppositories are inserted with the fingers,
but certain vaginal suppositories may be inserted
with the aid of an appliance
➢Suppositories are introduced into body cavities for
local or systemic effects.
7

Local action
➢Medicaments are retained within the cavity for
local effects
➢Rectal suppositories intended for local action are
most frequently used to
✓ Relieve constipation, pain, irritation, itching, and
inflammation associated with hemorrhoids or
other anorectal conditions.
8

Local action…
➢Vaginal suppositories or inserts intended for local
effects
✓ Are employed mainly as contraceptives,
antiseptics in feminine hygiene, and as specific
agents to combat an invading pathogen
➢Urethral suppositories may be antibacterial or a
local anesthetic preparation for a urethral
examination.
9

Introduction…
Systemic action
➢For systemic effects, the mucous membranes of the
rectum and vagina permit the absorption of many
soluble drugs
➢The rectum is used frequently as the site for the
systemic absorption of drugs
10

Advantages of Suppositories
➢ Can exert a local effect on the rectal mucosa
➢ Used to promote evacuation of bowel
➢ Avoid any gastrointestinal irritation
➢ Drugs destroyed by portal circulation may bypass
the liver after rectal absorption
11

Advantages of Suppositories…
➢Convenient for the administration of drugs to
patients who are unable or unwilling to swallow
medication
➢Avoid drugs inactivation by the pH or enzymatic
activity of the stomach or intestines
➢People suffering from severe nausea or vomiting
12

Disadvantages of suppositories
➢The problem of patient acceptability
➢Suppositories are not suitable for patients suffering
from diarrhea
➢Not suitable for drugs that irritate rectal mucosa
➢Incomplete absorption may be obtained
13

Disadvantages of suppositories…
➢ The industrial manufacture of suppositories is
more difficult than for other common dosage
forms
➢ Rectal administration of therapeutic agents may
result in the development of local side-effects
➢ Specialist advice is required concerning the
administration of dosage forms
14

Types of suppositories
➢Rectal suppositories
➢Vaginal suppositories
➢Urethral suppositories (bougies)
➢Nasal suppositories (nasal bougies)
➢Ear cones
15

Rectal suppositories
➢Usually about 32 mm long, are cylindrical and have
one or both ends tapered and some are shaped like a
bullet or the little finger
➢The weight may vary
✓ Rectal suppositories for adults weigh 2 gm (cocoa
butter)
✓ Children's suppositories weigh about 1 gm
16

Mode of insertion of suppositories
➢Remove suppository from its package
➢Insert a small tapered end first with the index
finger and push it for about1inch of the finger
➢May need to be lubricated with a water-soluble gel
to ease insertion
➢The use of an examination glove or a finger cot
can ease insertion by protecting the rectal wall from
fingernail
17

➢Vaginal suppositories or pessaries weigh about 4-
8gm and are molded in globular or oviform shape
or compressed on a tablet press into conical shapes.
➢Pessaries are used almost exclusively for local
medication, the exception being prostaglandin
pessaries that do exert a systemic effect.
Vaginal suppositories
18

➢They contain one or more active substances
dispersed or dissolved in a suitable base that may be
soluble or dispersible in water or may melt at body
temperature.
19
Vaginal suppositories
19

Application should follow a specific technique:
➢Begin with an empty bladder and washed hands
➢Open the container and place the dose in an
applicator
➢Lubricate applicator with water-soluble lubricant if
not pre-lubricated
20
20

Application should follow a specific technique…
➢Lie down, spread the legs, open the labia with one
hand, and insert the applicator about two inches into
the vagina with the other hand
➢Release labia; use a free hand to push the applicator
plunger
➢Withdraw the applicator and wash the hands
21

Urethral suppositories
➢Urethral suppositories called bougies are pencil
shape
➢Those intended for males weigh 4 gm each and are
100-150 mm long.
➢Female urethral suppositories are 2 gm and 60-75
mm long
➢Used to treat incontinence and impotence in men
➢Disadvantages
✓Inconvenience of localized pain
22

Nasal suppositories
➢ Called nasal bougies or buginaria meant for
introduction into the nasal cavity
➢ They are prepared with a glycerogelatin base
➢ They weigh about 1 gm
Ear cones
➢ Aurinaria and meant for introduction into the ear.
➢ Rarely used
➢ Theobroma oil is used as a base.
23

Formulations
➢Suppositories are drug delivery systems where the
drugs are incorporated into an inert vehicle called a
suppository base
➢The physicochemical properties of both the
therapeutic agent and suppository base are important
determinants of the clinical and non-clinical
performance of suppositories 24

Suppository Base
Ideal Suppository Base
1. Melts at body temperature or dissolves in body
fluids.
2. Non-toxic and non-irritant.
3. Compatible with medicament.
4. Releases any medicament readily.
25

Ideal Suppository Base…
5. Easily molded and removed from the mold.
6. Stable to heat above the melting point.
7. Easy to handle.
8. Stable on storage.
26

Suppository Base...
Types of suppository bases
➢Two types of suppository bases:
1. Fatty Bases
✓ Are designed to melt at body temperature.
2. Water-soluble or miscible bases
✓ Are designed to dissolve or disperse within the
body fluids.
27

Suppository Bases…
I- Fatty Bases
➢ Composed of naturally occurring or
semisynthetic/synthetic fatty acid esters of
glycerol
➢Designed to melt at body temperature within the
rectum thereby facilitating drug release and
subsequent dissolution
28

A- Theobroma oil (Cocoa butter)
➢It is a yellowish-white solid with an odor of
chocolate
➢It is a natural material that consists of
✓ A mixture of fatty acid (e.g. stearic, palmitic, and
oleic) esters of glycerol, predominantly triesters
✓ e.g. glyceryl tripalmitate
29

Theobroma oil (Cocoa butter)…
➢The presence of unsaturated (e.g. oleic acid) esters
contributes to the low melting point of cocoa butter
(30-36oC)
✓ Facilitate cocoa butter melting following
insertion within the rectum
30

Theobroma oil (Cocoa butter)…
➢The incorporation of lipophilic drugs into cocoa
butter lowers the melting-point range of
suppositories
✓ Lead to stability problems and
✓ Result in suppositories that are too soft to insert
➢To overcome this problem, beeswax (4% w/w) or
cetyl esters wax (20% w/w) may be added to the
suppository
31

Advantages of fatty bases
➢ A melting range of 30 - 36°C
➢ Readily melted on warming, rapid setting on
cooling
➢ Compatible with many ingredients
➢ Cocoa butter is safe, non-toxic and non-irritating
32

Disadvantages of fatty bases
➢Polymorphism
✓ Cocoa butter exists in four polymorphic forms:
❖ Alpha (α, melting point 20°C);
❖ Beta (β, melting point 34–35°C);
❖ Beta prime (β', melting point 28°C); and
❖ Gamma (γ, melting point 34–35°C)
33

Disadvantages of fatty bases…
➢ When melted and cooled it solidifies in these
different crystalline forms, depending on
✓ Temperature of melting
✓ Rate of cooling and
✓ Size of the mass
➢ If melted at not more than 36°C and slowly cooled
it forms stable β crystals (34-35 °C)
34

➢If over-heated then cooled it produces unstable β’
crystals which melt at about 28°C or α crystals
melting at 20°C.
➢Cocoa butter must be slowly melted over a warm
water bath to avoid the formation of the unstable
crystalline form.
35

➢Melting point too low for hot climates
➢Melting point reduced by soluble ingredients
(lipophilic)
✓ Phenol and chloral hydrate have a tendency to
lower the melting point of cocoa butter
✓ So, solidifying agents may be incorporated to
compensate for the softening effect of the
added substance
36

➢Adherence to the mold
➢Rancidity in storage
➢Poor water-absorbing ability
✓Improved by the addition of emulsifying agents
➢Leakage from the body
✓Seldom used in vaginal suppositories
➢Expensive
37

B. Synthetic Hard fat
➢Are composed of mixtures of triglycerides of higher
saturated fatty acids (ranging from C8H17COOH to
C18H37COOH) and di/monoglycerides
➢As an alternative for theobroma oil
➢For example, Suppocire, witepsol.
38

Advantages of synthetic Hard Fat
➢They have good resistance to oxidation because of
the lower content of unsaturated fatty acids
➢The difference between melting and setting points
is small
✓ Hence they set quickly, and the risk of
sedimentation of suspended ingredients is low
39

Advantages of synthetic Hard Fat…
➢Their solidifying points are unaffected by
overheating
➢They are marketed in a series of grades with
different melting point ranges, which can be chosen
to suit particular products and climatic conditions
40

Advantages of synthetic Hard Fat…
➢They contain a proportion of w/o emulsifying
agents, and therefore, their water-absorbing
capacities are good
➢No mold lubricant is necessary because they
contract significantly on cooling
41

Disadvantages of synthetic Hard Fat
➢Brittle if cooled rapidly, avoid refrigeration during
preparation
➢The melted fats are less viscous than theobroma oil
✓ As a result there is a greater risk of
❖ Drug particles to sediment during preparation
❖ Lack of uniform drug distribution gives
localized irritancy
42

Choice of synthetic/semi-synthetic bases
➢Hydroxyl number
✓ The measure of the presence of mono- and
diglycerides in the suppository base
✓ The available suppository bases range in
hydroxyl numbers from 5 to 15
43

Choice of synthetic/semi-synthetic bases…
Melting properties
➢Low MP bases (370C) are generally used for the
formulation of suppositories in which systemic
absorption of the therapeutic agent is desired
➢Bases of higher MP are frequently used in
formulations in which a local effect is desired
44

➢The melting properties of the base should be
considered in conjunction with the solubility of the
chosen therapeutic agent
✓ If the active agent is soluble in the base, this will
lead to a reduction in the melting point of the
base
➢Consideration of the solubility of the therapeutic
agent within both the molten and cooled base is
important
45

The viscosity of the melted base
➢Can affect the performance of suppositories in two
ways
✓ During manufacturing, affect both the mixing of
the drug with the molten base and the flow of the
molten dispersion into the molds
✓ During use affects the spreading of the
formulation on the rectal mucosa and the
subsequent drug release
46

II. Water-soluble and water-
miscible bases
➢A- Glycero-gelatin base (Water-
soluble)
✓ The required drug is dissolved
or dispersed within this base.
Suppository base…
47

Glycero-gelatin base (Water-soluble)…
➢This suppository base is prepared by dissolving
gelatin (20% w/w) in glycerol (70% w/w) with the
aid of heating (100oC).
➢The required drug is generally dissolved/dispersed
in an aqueous phase ( 10% w/w) and then combined
with the glycerol phase with stirring prior to pouring
into the suppository mould. 48

➢The mechanical properties of the formed suppository
may be manipulated by
✓ Increasing or decreasing the mass of added gelatin
➢As the mass of added aqueous phase is increased, the
suppositories will become softer, thereby leading to
potential problems regarding their insertion by the
patient
✓ Increasing the concentration of gelatin will negate
this effect
49

➢ Glycerinated gelatin usually is used as a vehicle for
vaginal suppositories
➢ For rectal use a firmer suppository can be obtained
by increasing the gelatin content
➢ e.g. in Gelato-glycero suppositories BP the
concentrations of an aqueous phase, gelatin, and
glycerol are 27.5% w/w, 32.5% w/w, and 40% w/w,
respectively
50

➢In urethral suppositories the ratio of gelatin to
glycerol to water (containing the active agent) is
3:1:1.
➢The enhanced mechanical properties facilitate
insertion into the urethra.
51

Disadvantages of Glycero-gelatin base
➢Long preparation time
✓ Lubrication, heat treatment
➢Lubrication of the mold is essential
➢Microbial contamination likely
Suppository base…
52

Disadvantages of Glycero-gelatin base…
➢Hygroscopic:
✓ Must be carefully packaged to prevent moisture
uptake
✓ Lead to dehydration and irritation of the rectal
and vaginal mucosa.
❖ This action prompts bowel evacuation.
❖ Reduced by: dip the preparation in water before
insertion
53

➢Potential interactions with therapeutic agents
✓pH of aqueous solutions of gelatin type will affect
the ionization
❖ Type A acts as a base if formulated at a pH < 7
and type B will act as an acid if the pH > 5.3?
54

➢ Gelatin interacts with therapeutic agents of
opposite charge in a typical acid-base
interaction
✓ Lower the solubility of gelatin and may lead
to precipitation
55

Suppository base…
B- Water-miscible bases (Macrogols)
➢Composed mainly of PEGs possessing a molecular
weight greater than 1000 g/mol
➢The melting point of these higher grades of PEGs
increases as the molecular weight increases
➢e.g. the melting points of PEG 1000 and PEG
8000 are 37–40oC and 60–63oC, respectively
56

Water-miscible bases (Macrogols) …
✓ Typically the melting point of PEG suppository
bases is around 42 oC
➢PEGs having average Mwt < 600 are clear,
colorless liquids, while those with Mwt of 600-1000
are semisolids
57

➢Those having average Mwt > 1000 are wax-like,
white solids with the hardness increasing with an
increase in the molecular weight.
➢These PEGs can be blended together to produce
suppository bases with varying melting points,
dissolution rates, and physical characteristics.
58

➢Following insertion into the rectum, these
suppositories will not melt but will instead
gradually dissolve
➢Enable drug dissolution to occur
➢Higher proportions of high Mwt polymers produce
preparations that release the drug slowly and are
also brittle.
59

Suppository base…
Advantages of macrogols
➢ The melting point is often around 42°C.
✓ Can be used in hot climates
✓ Do not melt in the body but gradually dissolve
and disperse so that they release their
medication slowly and provide longer action
than the fatty base
➢ Do not leak from the orifice
60

Advantages of macrogols…
➢ Products that release the drug more readily can
be prepared
➢ No need of lubrication of the mold
➢ Because of their HMWt, solutions of high
viscosity are produced
➢Leakage is not a serious problem
➢ They absorb water well and hence excellent
solvent properties
61

Suppository base…
Disadvantages of macrogols
1. Hygroscopic
✓ Problem of irritancy
2. Reduced therapeutic activity
✓ Due to good solvent property retention of the
drug in the liquefied base may occur.
3. Brittleness
✓ Surfactants and plasticizers may reduce this
problem
4. Crystal growth of some medicaments
62

Miscellaneous Bases
➢Mixtures of oleaginous and water-soluble or water-
miscible materials.
➢These materials may be chemical or physical
mixtures.
➢Some are pre-formed emulsions
✓Generally of the water-in-oil type, or
✓They may be capable of dispersing in aqueous
fluids.
63

Miscellaneous Bases…
✓One of these substances is polyoxyl 40 stearate, a
surface-active agent that is employed in a number
of commercial suppository bases.
➢There are mixtures of many fatty bases (including
cocoa butter) with emulsifying agents capable of
forming water-in-oil emulsions.
✓Hold water or aqueous solutions that are said to
be hydrophilic.
64

Other additives
Surface-active agents
➢Enhance the wetting properties of the suppository
base with the rectal fluid
✓ Enhance drug release/dissolution
➢For formulations composed of a lipophilic
suppository base and/or a lipophilic drug
✓ E.g. sorbitan esters and polyoxyethylene sorbitan
fatty acid esters
65

Other additives…
Agents to reduce hygroscopicity
➢Reduce the uptake of water from the atmosphere
during storage
✓ Enhance the physical and chemical stability of
the dosage form/therapeutic agent
➢e.g. colloidal silicon dioxide
66

Other additives…
Agents to control the melting point of the base
➢The melting point of the base may be manipulated to
enhance the mechanical properties and physical
stability of the suppository in response to
✓The deleterious effects of storage at higher
temperatures and/or
✓The presence of a therapeutic agent that is soluble
in the suppository base.
67

Other additives…
➢Excipients to increase MP of suppositories prepared
using fatty bases
✓ Beeswax (white or yellow wax)
✓ Stearic acid
✓ Aluminium mono- or distearate
✓ Colloidal silicon dioxide
✓ Magnesium stearate
✓ Bentonite.
68

Other additives…
➢Excipients to reduce the MP of the fatty suppository
base to enable melting within the rectum
✓ Glyceryl monostearate
✓ Myristyl alcohol
✓ Polysorbate 80
✓ Propylene glycol
69

Other additives…
➢The MP of PEG-based suppositories may be
controlled by altering the grade of PEG used
✓ The MP can be increased by the inclusion of
HMwt PEG
✓ The MP of water-miscible suppository bases
can be lowered by incorporating the required
concentration of LMwt PEG
70

Other additives…
➢Antioxidants
➢Preservatives: for water-soluble bases
➢Emulsifying agents
✓ Such as emulsifying wax, wool fat, wool
alcohol can be used to facilitate the
incorporation of an aqueous solution
➢Viscosity modifiers such as magnesium stearate,
bentonite
71

Preparation of suppositories
➢Suppositories are prepared by three methods:
✓Molding from a melt
✓Compression, and
✓Hand rolling and shaping
72

Preparation of suppositories…
➢The steps in molding include
✓Melting the base
✓Incorporating any required medicaments
✓Pouring the melt into molds
✓Allowing the melt to cool and congeal into
suppositories and
✓Removing the formed suppositories from the mold
73

Suppository Molds
➢Can produce individual or large numbers of
suppositories of various shapes and sizes.
✓Individual plastic molds form a single suppository.
✓Other molds are capable of producing 6, 12, or
more suppositories in a single operation
74

Suppository Molds…
✓ Industrial molds produce hundreds of
suppositories from a single batch
➢Molds in common use today are made from
stainless steel, aluminum, brass, or plastic.
➢The molds are opened for cleaning before and after
preparation of a batch of suppositories, closed when
the melt is poured, and opened again to remove the
cold, molded suppositories.
75

Lubrication of the Mold
➢Depending on the formulation, suppository molds
may require lubrication before the melt is poured to
facilitate cleaning and easy removal of the molded
suppositories
➢Not used if the base is the synthetic fatty base or
polyethylene glycol
➢Usually necessary with glycerinated gelatin and
cocoa butter.
76

Pour molding
77
➢Theobroma
oil
➢Glycerol-
gelatin base
➢Soap spirit
➢Liquid paraffin
or arachis oil
➢Synthetic fats
➢Macrogols
Base Lubricant No lubricant
required
Lubricants for use with suppository bases

Calibration of the Mold
➢Each individual mold is capable of holding a
specific volume of material in each of its openings.
➢Calibrate each suppository mold for the usual base
so as to prepare medicated suppositories each having
the proper quantity of medicaments.
78

➢The first step in calibration of a mold is to prepare
molded suppositories from base material alone.
➢After removal from the mold, the suppositories are
weighed and the total weight and average weight of
each suppository are recorded
79

➢To determine the volume of the mold, the
suppositories are carefully melted in a calibrated
beaker, and the volume of the melt is determined for
the total number and for the average.
80

Determination of the Amount of Base Required
➢Three methods of calculating the quantity of base
that the active medication will occupy and the
quantities of bases required are
✓ Density factor
✓ Occupied volume methods
✓ Dosage replacement factor 81

Density factor method
1. Determine the average blank weight, A, per mold
using the suppository base of interest
2. Weigh the quantity of suppository base necessary
for 10 suppositories
3. Weigh 1.0 g of medication. The weight of
medication per suppository, B, is equal to 1 g/10
supp = 0.1 g/supp
82

Density factor method…
4. Melt the suppository base and incorporate the
medication, mix, pour into molds, cool, trim, and
remove from the molds
5. Weigh the 10 suppositories and determine the
average weight (C)
83

6. Determine the density factor as follows:
where
➢A is the average weight of blank,
➢B is the weight of medication per suppository, and
➢C is the average weight of medicated suppository.
84

7. Take the weight of the medication required for
each suppository and divide by the density factor of
the medication to find the replacement value of the
suppository base
8. Subtract this quantity from the blank suppository
weight
85

9. Multiply by the number of suppositories required
to obtain the quantity of base required for the
prescription
10. Multiply the weight of drug per suppository by
the number of suppositories required to obtain the
quantity of active drug required for the prescription
86

Example
➢Prepare 12 acetaminophen 300 mg suppositories
using cocoa butter. The average weight of the cocoa
butter blank is 2 g and the average weight of the
medicated suppository is 1.8 g.
87

Exercise
➢Determine the amount PEG base required to prepare
10 progesterone 600 mg suppositories. The average
weight of the PEG base blank is 2.2 g and the
average weight of the medicated suppository is 1.9
g.
88

Determination of occupied volume method
1. Determine the average weight per mold (blank)
using the designated base.
2. Weigh out enough base for the required numbers of
suppositories.
3. Divide the density of the active drug by the
density of the base to obtain a ratio.
89

Determination of occupied volume method …
4. Divide the total weight of active drug required for
the total number of suppositories by the ratio
obtained in step 3. This will give the amount of base
displaced by the active drug.
90

5. Subtract the amount obtained in step 4 from the
total weight of the prescription (number of
suppositories multiplied by the weight of the blanks)
to obtain the weight of base required.
6. Multiply the weight of active drug per suppository
times the number of suppositories to be prepared to
obtain the quantity of active drug required. 91

Example
➢Prepare 10 suppositories, each containing 200 mg of
a drug with a density of 3.0. The base has a density
of 0.9, and a prepared blank weighs 2.0 g. Using the
determination of occupied volume method, prepare
the requested suppositories.
92

Exercise
➢Determine the amount base required to prepare 12
progesterone 600 mg suppositories. The density of
the base 1.2 and that of the API is 3.6. a prepared
blank weighs 2.2 g.
93

The dosage replacement factor method
➢Where E is the weight of the pure base
suppositories, and
➢G is the weight of suppositories with X% of the
active ingredient.
94

The dosage replacement factor method…
Exercise: Prepare 12 suppositories containing 100 mg
of phenobarbital (f = 0.81) using cocoa butter as the
base. The weight of the pure cocoa butter
suppository is 2.0 g. Because 100 mg of
phenobarbital is to be contained in an approximately
2.0 g suppository, it will be about 5% phenobarbital.
What will be the total weight of each suppository
and the amount of base required?
95

➢The displacement factor may be visualized as the
weight of the drug required to displace the unit
weight of the base.
✓For example, the displacement value of
phenobarbital is 0.81 for cocoa butter. Therefore
0.81 grams of this therapeutic agent will displace 1
gram of cocoa butter. And also expressed as
BY: Aychew M. IPP II(PHAR (3121) 2014EC 96

➢In practice the displacement value is calculated as
follows:
✓The average weight of the suppository mold is
calculated using the blank suppository base.
✓The weight of drug needed for the total number of
suppositories are calculated
✓The average weight of the suppositories after
adding the mass of the drug to the notional mass
of the suppository base.

Example
1. Determine the displacement value for a therapeutic
agent in a triglyceride base. The concentration of
drugs in each suppository should be 10% and the
weight of six blank and medicated suppositories are
6gm and 6.11gm respectively.
2. Prepare six (2-gram) suppositories containing 5%
phenobarbital (displacement value of 0.81). Calculate
the final formulae for the requested dosage form.

➢Although the above calculations are primarily
directed to fatty bases
➢This argument may be extended to water-soluble
and water-miscible systems in which the drug has
been dispersed.
➢In glycerol–gelatin suppositories the calculated
amount of base is increased by a factor of 1.2

➢Displacement values are not considered
✓In the formulations in which the drug is soluble in
the base.
✓In the formulations in which the volume occupied
by the powder is insignificant
❖e.g. active drug less than100 mg in 2gm mold.

Preparing and Pouring the Melt
➢The weighed suppository base material is melted in
a porcelain dish
➢Usually, medicinal substances are incorporated into
a portion of the melted base by mixing on a glass or
porcelain tile with a spatula.
➢After incorporation, this material is stirred into the
remaining base, which has been allowed to cool
almost to its congealing point.
101

Preparing and Pouring the Melt…
➢Any volatile materials or heat-labile substances
should be incorporated at this point with thorough
stirring.
➢The melt is poured carefully and continuously into
each cavity of the mold, which has been previously
equilibrated to room temperature.
102

➢If any undissolved or suspended materials in the
mixture are denser than the base so that they have a
tendency to settle, constant stirring, even during
pouring, is required
➢The solid materials remain suspended if the pouring
is performed just above the congealing point and not
when the base is too fluid.
103

➢In filling each suppository cavity, the pouring must
be continuous to prevent layering, which may lead
to a product easily broken on handling.
➢To ensure a completely filled mold upon
congealing, the melt is poured excessively over each
opening, actually rising above the level of the mold
104

➢When solidified, the excess material is evenly
scraped off of the top of the mold with a spatula
warmed by dipping into a beaker of warm water
➢This will make a smooth surface on the back of the
suppository during trimming.
105

➢The mold is usually placed in the refrigerator to
hasten hardening.
➢When the suppositories are hard, the mold is
removed from the refrigerator and allowed to come
to room temperature.
106

➢Then the sections of the mold are separated, and the
suppositories are dislodged, with pressure being
exerted principally on their ends and only if needed
on the tips.
➢Generally, little or no pressure is required, and the
suppositories simply fall out of the mold when it is
opened.
107

Compression molding
➢ The cold mass of the base containing the drug is
compressed into suppositories using a hand-
operated machine.
➢ Suppositories may be prepared by forcing the
mixed mass of the base and the medicaments into
special molds using suppository-making machines.
108

Compression molding…
➢In preparation for compression into the molds, the
base and the other formulation ingredients are
combined by thorough mixing, the friction of the
process softening the base into a paste-like
consistency.
➢On a small scale, a mortar and pestle may be used.
109

➢Heating the mortar in warm water (then drying it)
greatly facilitates the softening of the base and the
mixing.
➢On a large scale, a similar process may be used,
employing mechanical kneading mixers and a warm
mixing vessel.
110

Advantages:
1. It is a simple method.
2. It gives suppositories that are more elegant than
hand molded suppositories.
3. In this method sedimentation of solids in the
base is prevented.
4. Suitable for heat labile medicaments.
111

Disadvantages:
➢ Air entrapment may take place.
✓ This air may cause weight variation.
✓ The drug and/or the base may be oxidized by this
air.
➢Special suppository machine is required
➢Limitation as to the shapes of suppositories that can
be made.
112

Hand molding
➢Hand molding is useful when we are preparing a
small number of suppositories:
1. The drug is made into a fine powder.
2. It is incorporated into the suppository base by
trituration in a mortar.
3. The mixed mass is rolled between fingers into
rod-shaped units.
4. The rods are cut into pieces and then one end is
pointed.
113

Packaging, labeling, and storage
➢PEG suppositories and glycerinated gelatin
suppositories are packaged in tightly closed glass
containers
➢Suppositories prepared from a cocoa butter base are
usually individually wrapped or otherwise separated
in compartmented boxes
➢Suppositories containing light-sensitive drugs are
individually wrapped in an opaque material
114

Packaging and storage…
➢Some are packaged in a continuous strip, separated
by tearing along perforations.
➢Cocoa butter suppositories must be stored below
30°C, and preferably in a refrigerator (2°C to 8°C)
➢Glycerinated gelatin suppositories can be stored at
controlled room temperature (20°C to 25°C)
115

116

Packaging and storage…
➢Suppositories made from a base of PEG may be
stored at usual room temperatures.
➢Suppositories stored in high humidity may absorb
moisture and tend to become spongy, whereas
suppositories stored in places of extreme dryness
may lose moisture and become brittle.
117

2. Suppositories 2014.pdf

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2. Suppositories 2014.pdf