Lecture 3
Suppositories
Pharmaceutical dosage form II
course
Asmaa A. Ashour, PhD.
Lecture Outline
▪ Water dispersible bases (PEG)
▪ Methods of preparation of suppositories
▪ Packaging and storage
▪ Methods of evaluation of suppositories
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Types of suppository bases
Fatty bases Water soluble Water miscible
bases bases
Cocoa butter Poly-
Gelato-glycerin ethylene
glycol (PEG)
Semisynthetic
glycerides or
hard fat (Cocoa
butter
substitutes)
Water miscible bases (PEG = macrogol)
Properties
▪long chain polymers of ethylene oxide with general formula
HOCH2(CH2OCH2)8CH2OH.
▪Lower molecular weight PEGs (PEG 400 and 600) are liquid,
those around 1000 are semi-solid and those above 4000
are waxy solids.
▪Their water solubility and hygroscopicity decreases with
increasing their molecular weight.
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Water miscible bases (PEG = macrogol)
Physical
properties of
different PEGs
Water miscible bases (PEG = macrogol)
Properties
▪ The melting point of these vehicles is above body temperature,
which means that they need to mix with the rectal fluid.
▪ PEGs of all molecular weights are miscible with water and rectal
fluids, thereby releasing drug by dispersion; as the available
volume of rectal fluid (1-3 mL) is too small for true dissolution.
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Water miscible bases (PEG = macrogol)
▪ Blend of PEG of different Mwt may be combined by fusion and are
used as suppository bases of desired consistency and characteristics.
Composition Base A Base B Base C
PEG 400 20%
PEG 1000 95% 75 %
PEG 1540 30%
PEG 4000 5% 25 %
PEG 6000 50 %
Properties Low melting Higher melting General purpose
temperature, temperature, base and for
immediate drug sustained drug intermediate
release release drug release
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Water miscible bases (PEG = macrogol)
Advantages
1.They do not hydrolyze or deteriorate and are physiologically inert.
2.Because of their high melting point, PEG based formulations are suited for
application in tropical climates.
3.Because they mix with rectal fluids, leakage from rectum is less likely to
occur.
4.Microbial contamination is less common (no need for refrigeration or
addition of preservative).
5.No need for mold lubrication.
6.They are suitable for drugs which tend to reduce the m.p. of the base , such
as chloral hydrate.
7.They are of high viscosity, so no drug sedimentation occur.
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Water miscible bases (PEG = macrogol)
Disadvantages
1.They are hygroscopic and therefore attract water from the tissues after
insertion , resulting in a painful sensation for the patient.
▪ The incorporation of at least 20% water in their composition and
moistening before insertion can help to reduce this problem.
2.Due to hygroscopicity, they should be protected from moisture.
▪ As the molecular weight of PEG decreases as the hygroscopicity
increases so careful storage is required.
3.A considerable number of incompatibilities;
▪ drugs such as bismuth salts and phenolic compounds (aspirin,
salicylates) and phenobarbitone.
▪ They dissolve certain plastics necessitating care in choosing containers
Water miscible bases (PEG = macrogol)
Disadvantages
4. PEG bases can develop peroxides on storage due to polyoxy ethylene
linkage, therefore airtight packaging, protected from light is recommended
and the formulation should be monitored for peroxides why?
5. Brittleness which could occur when the base is cooled rapidly.
To overcome this problem
▪ Pouring the base near the solidification point to avoid rapid cooling.
▪ Avoid cooling in refrigerator.
▪ Addition of plasticizer, as glycerin, propylene glycol or low molecular
weight PEG.
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5
Methods of Preparation of
suppositories
Fusion molding
Hand rolling Compression molding
(All types of bases)
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Methods of preparation of suppositories; 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.
▪ This technique generally uses cocoa butter, as it can easily be
manipulated, shaped, and handled at room temperature.
▪ It has the advantage of avoiding the necessity of heating the cocoa
butter (prevention of polymorphism).
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Methods of preparation of suppositories; Hand rolling
A plastic-like mass is prepared by triturating grated cocoa butter
and active ingredients in a mortar
The mass is formed into a ball in the palm of the hands, then
rolled into a uniform cylinder
The cylinder is then cut into the appropriate number of pieces
which are rolled on one end to produce a conical shape
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Hand rolling
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Methods of Preparation of
suppositories
Fusion molding
Hand rolling Compression molding
(All types of bases)
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Compression molding
▪ It is a method of preparing suppositories from a mixed mass of grated
suppository base and medicaments which is forced into a special compression
mold.
▪ The suppository base and the other ingredients are combined by thorough
mixing.
▪ The friction of the process causing the base to soften into a paste-like
consistency.
▪ On a small scale, a mortar and pestle may be used (preheated mortar
facilitate softening of the base).
▪ On large scale, mechanically operated kneading mixers and a warmed
mixing vessel may be applied.
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Compression molding
▪ 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.
▪ When the die is filled with the mass, a
movable end plate at the back of the die is
removed and when additional pressure is
applied to the mass in the cylinder, the
formed suppositories are ejected.
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Compression molding
▪ It Useful for molding suppositories
containing insoluble solids (no risk of
sedimentation) or thermolabile
medicaments.
▪ This method is not suitable for
preparation of gelato-glycerin
based suppositories or other bases
that require heating during
preparation.
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Methods of Preparation of
suppositories
Fusion molding
Hand rolling Compression molding
(All types of bases)
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Fusion molding
Dispersing or The mixture is
Melting the
dissolving the drug in removed from the heat
suppository base
the melted base. and poured into a
suppository mold.
Removing the formed
suppositories from the
mold.
Allowing the melt to
congeal
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Fusion molding
▪Small scale molds can produce 6
or 12 suppositories in a single
operation.
▪ Industrial molds produce
hundreds of suppositories from a
single molding.
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Fusion molding
Lubrication of the mold
▪ It may be needed before the melt is poured to facilitate removal of the
molded suppositories.
▪ Lubrication is not necessary when the base is polyethylene glycol, as this
material contract sufficiently on cooling to separate from the inner
surfaces and allow easy removal.
▪ Lubrication is usually necessary with gelato-glycerin suppositories with a
thin coating of mineral oil and for cocoa butter suppositories with thin
layer of soap solution applied to the surface of the mold.
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Packaging and storage
▪Some commercial suppositories are individually wrapped
in either foil or plastic.
▪Most are packaged in a continuous strip, separated by
tearing along perforations.
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Packaging and storage
Suppositories • Individually wrapped in an opaque material such
containing light- as a metallic foil
sensitive drugs
Cocoa butter-
• individually wrapped to prevent contact and
based
adhesion
Suppositories
Glycerinated
gelatin and PEG • Packaged in tightly closed packages to prevent a
suppositories change in moisture content
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Packaging and storage
Cocoa butter &
Fatty based
suppositories Gelato-glycerin PEG suppositories
suppositories.
• Adversely • Must be stored • Stored at usual
affected by heat below 30 °C and room
• Should be stored preferably in a temperatures but
at cool place refrigerator (2°C not wrapped in
to 8°C). plastic
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Why should we perform product
evaluation?
Ensure drug Avoid variation
safety and between different
efficacy batches
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When are Quality control tests performed?
During
storage
On the finished
product
During
manufacturing
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Quality control tests of suppositories
Visual Weight Content
examination uniformity test uniformity test
Melting range
test Breaking test Drug release test
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1. Visual examination (Appearance)
Suppositories can be observed as an intact unit and by splitting them
longitudinally.
Suppositories are examined for:
▪ absence of fissuring
▪ pitting
▪ fat blooming
▪ sedimentation
▪ the migration of the active ingredients
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2. Weight uniformity test
▪ Weigh 20 suppositories and calculate the average weight
▪ When each suppository is weighed, the deviation of individual weight
from the average weight should not exceed the limits given below:
% Deviation Number of suppositories
±5% Maximum 2
± 10 % none
N.B. The weight may decrease during storage when the suppositories
contain volatile substances, especially if the packaging is not airtight.
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3. Content uniformity test
▪ Suppositories must be analyzed to provide information on dose-to-
dose uniformity.
▪ Preparations with an active ingredient content of < 2 mg or < 2 % of
the total mass, comply with the test.
▪ A total number of 10 suppositories are selected randomly and the
content of the drug is determined by a suitable analytical method.
▪ Compare the individual content with the average one.
▪ The preparation complies with the test if not more than one of the
individual content is outside 85% to 115% of the average content.
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4. Melting range test (disintegration test)
▪ Macro-melting range is a measure that
determines the time taken by an entire
suppository to melt when it is immersed
in a constant temperature bath at 37°C.
What is Micro melting range???
▪ The experiment done by using the USP
Tablet Disintegration Apparatus.
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4. Melting range test (disintegration test)
▪ Suppository is completely immersed in the
constant temperature water bath, and the
time for the entire suppository to melt or
disperse in the surrounding water is
measured.
The determined time should be:
▪ not more than 30 min for fat-based
suppositories .
▪ not more than 60 min for water soluble
suppositories
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5. Breaking test (Hardness test)
▪ This test is used for the determination of the mechanical force
required to break a suppository. It indicates whether the suppository
is elastic or brittle.
▪ The purpose of the test is to verify that the suppository can be
transported under normal conditions, and administered to the patient
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5. Breaking test (Hardness test)
▪ The suppository is placed in a double wall
chamber through which water at 37 ˚C is
pumped.
▪ The suppository, contained in the dry inner
chamber, supports a disc to which rod is
attached. The other end of the rod consist of
another disc to which weights are applied.
▪ Add 600 g, leave it for one min.
▪ If not broken, add 200 g every one min. until
the suppository is broken.
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5. Breaking test (Hardness test)
▪ The weight at which the suppository collapses is the breaking
point.
▪ Suppositories can be classified as brittle or elastic by evaluating
the mechanical force required to break them.
▪ The mechanical or breaking force of the suppository should not be
less than 1.8-2 Kg.
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6. In-vitro drug release test
▪ It is measured by using the same melting range apparatus
(disintegration apparatus).
▪ Aliquots of the release medium (buffer of similar pH to that of the
rectum 7.4 or vaginal pH= 5) were taken at different time intervals
within the melting period.
▪ The drug content in the aliquots was determined.
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6. In-vitro drug release test
▪ The drug release pattern was plotted
(time versus-drug release curve).
▪ This test measures the % drug released
from suppositories in a specified period
(not less than 75% of drug is released
in 45 min).
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