LAB 6: SUPPOSITORY
PHARMACEUTICS I
LAB 6: SUPPOSITORY
PHARMACEUTICS I
melt to cool and congeal into suppositories, and (e) removing the formed suppositories
from the mold. The molding method is applicable to cocoa butter, glycerinated gelatin,
polyethylene glycol, and most other bases.
bases
Water bath
cool
incorporating
medications
melting
QC
trim
package
On the other hand, when the density of the active drug and the base is unknown, f
can be calculated using the following equation,
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LAB 6: SUPPOSITORY
W
G M W
PHARMACEUTICS I
where W is the weight of the active ingredient in each suppository, G is the weight of
the pure base suppository, M is weight of the suppository with X% of the active
ingredient.
Based on the displacement value the amount of base (E) to be added in each
suppository can be calculated using the following equation:
E G
W
f
(2)
It is important to note that the same drug substance has the different displacement
values for different bases. Therefore, the base type should be specified when
mentioning the displacement value.
For quality control of suppository, weight variation, melting time, overall
appearance, and hardness should be checked as prescribed in the Chinese
Pharmacopoeia (2005). Moreover, some other non-compendial parameters should be
tested, such as homogeneity, particle size, softening temperature, dissolution and
bioavailability.
3. METHODS
3.1 Measurement of the displacement value
Using aspirin as the model drug, determine its displacement value for semi-synthesis
glycerides.
3.1.1 Procedures
a) Prepare molded suppositories with base material alone: Weigh 10 g of semi-synthesis
glycerides and transfer it into a porcelain casserole, heat the dish using a water bath.
Remove the dish from the water bath when 2/3 of the base has melted and stir to
complete melting. When the base is cooled down close to its congealing point, pour
the melt into the cavities of the lubricated mold and allow the melt continue to cool
and congeal for forming suppositories. After trimming, remove the formed
suppositories from the mold. Weigh each suppository and determine the average
weight G (g) of the blank suppositories.
b) Prepare aspirin containing suppositories: Weigh 6 g of semi-synthesis glycerides and
transfer it into a porcelain casserole, heat the dish using a water bath. Remove the
dish from the water bath when 2/3 of the base has melted and stir to complete
melting. Weigh 3 g of aspirin powder (which was passed through a 100 mesh-screen),
incorporate the powder into the melted base by small amounts, and mix until
uniform. When the base is cooled down close to its congealing point, pour the melt
into the cavities of the lubricated mold and allow the melt to cool and congeal into
suppositories. After trimming, remove the formed suppositories from the mold.
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LAB 6: SUPPOSITORY
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Weigh each suppository and determine the average weight of aspirin containing
suppositories Mg, the amount of drug in the suppository is : W=MX%, where X
% is the percentage of aspirin in the base.
c) Calculate the displacement value (density factor): use equation (1) to calculate f value
of aspirin versus semi-synthesis glyceride by using the determined values of G and M
in (a) and (b).
3.1.2 Notes
a) Semisynthetic glyceride is a fatty base and its volume increases with the increase of
temperature. Pay attention to the temperature of the mixture before pouring it into
the cavity of the mold. If the temperature is too high, there may be the formation of
a matrix with a hollow center or a recessed dip. If an undissolved or suspended
drug in the mixture is denser than the base, it has a tendency to settle. In this case,
constant stirring, even during pouring, is required. Otherwise, the suppositories
formed in the cavities towards the end of the pouring process may contain a higher
drug contents. The solid drug can remain suspended if the pouring is performed just
above the congealing point of the base, at which the base is not too fluid. When
filling the cavities in the mold, the pouring must be continuous to prevent the
layering effect. To ensure a completely filled mold upon congealing, the melt is
poured to a level slightly above the surface of the mold. This is done to prevent the
formation of recessed dips at both ends of the suppository during the cooling and
congealing process. The mold is usually placed in the refrigerator to accelerate
hardening.
b) To ensure accuracy of the measured f value, the same mold should be used to
prepare the base suppositories and the drug containing suppositories.
3.1.3 Based on the f value, calculate the amount of base needed to prepare the following
formulation:
Aspirin
3.0g
Semisynthetic glyceride
q.s.
Cone-shaped rectal suppository
5 pieces
3.2 Preparation of glycerin suppositories
3.2.1 Formulation
Glycerin
10 g
Stearic acid
0.8 g
Sodium hydroxide
0.12 g
Distilled water
1.4 mL
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LAB 6: SUPPOSITORY
PHARMACEUTICS I
5 pieces
3.2.2 Procedures
Weigh the specified amounts of glycerin and heat to 100 using a water bath. Add
the fine powder of stearic acid, sodium hydroxide and distilled water, stir constantly, and
continue heating at 8595 until the mixture is clear. When the base is still hot, pour
the melt carefully into the cavities of the lubricated molds and allow the melt to cool and
congeal into suppositories. After trimming, remove the formed suppositories from the
mold.
3.2.3 Quality test
a) The suppository should be colorless/ almost colorless and transparent or semitransparent.
b) Measure the weight variation
c) Test the melting time of the prepared suppositories.
3.3 Preparation of chlorhexidinie acetate( ) suppositories
3.3.1 Formulation
Chlorhexidinie acetate(Pass 100 mesh screen) 0.25 g
Tween-80
1.0 g (:1.061.09)
Borneol spirit
2.5 mL
Glycerin
32.0 g
Gelatin
9.0 g
Distilled water
add to 50.0mL
Vaginal suppository (Duck tongue shape)
10 pieces
3.3.2 Procedures
a) Preparation of borneol spirit: Weigh 0.5 g of borneol and dilute to 25 mL with
95% ethanol.
b) Preparation of glycerin-gelatin solution Weigh the predetermined amount of
gelatin and transfer it into a pre-weighed porcelain casserole followed by adding
1.5~2 times of distilled water for the soaking of the gelatin until softened. Pour
out the excess amount of water and heat the dish using a water bath to yield a
molten gelatin solution. Subsequently, add the predetermined amount of glycerin
(weighed), heat and stir the mixture continuously to evaporate the water until the
prescribed weight was obtained (net weight appro. 46.25 g).
c) Preparation of suppositoriesMix the specified amount of chlorhexidinie acetate,
Tween-80 and borneal spirit until uniform, then add the mixture into the glyceringelatin solution prepared in (b) and stir until uniform. When the mixture is still
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LAB 6: SUPPOSITORY
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hot, pour the melt into the cavities of the lubricated mold, allowing the melt to
cool down and eventually congeal into suppositories. After trimming, remove the
formed suppositories from the mold.
3.3.3Notes
a) An appropriate amount of water should be added to the gelatin to allow for proper
swelling before heating, otherwise, longer time is needed for mixing and there may
be undissolved gelatin pieces or granules remaining in the solution.
b) While stirring the mixture in (a), it is important to avoid the introduction of air
bubbles.
c) Water content in the glycerin-gelatin base is critical and should be controlled. Proper
control of the evaporation of water to attain the prescribe water content is important
to avoid making the suppositories too soft or too hard.
3.3.4 Test and evaluation
Appearance a pharmaceutically acceptable suppository product should have a
smooth surface without bubbles, is light yellow in color, transparent, and with a good
elasticity.
3.4 Preparation of matrine( ) suppositories
3.4.1 Formulation
Matrine
0.25 g
Borneol spirit
2.5 mL
Polyoxyl40stearate
47 g
Vaginal suppository (Duck tongue shape) 10 pieces
3.4.2 Procedures
Mix matrine and borneol spirit until uniform followed by adding the mixture into
melted polyoxyl (40) stearate (in the water bath) under constant stirring. When the mixture
is still hot, pour the melt in the cavities of the lubricated mold, allowing the melt to cool
down and congeal into suppositories. After trimming, remove the formed suppositories
from the mold.
3.4.3 Test and evaluation
Appearance: a pharmaceutically acceptable suppository product should have a smooth
surface without bubbles, is light yellow in color and transparent.
4. RESULTS AND DISCUSSION
4.1 Record the displacement value of aspirin for semisynthetic glyceride. Discuss in what
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LAB 6: SUPPOSITORY
PHARMACEUTICS I
5. QUESTIONS
a) Discuss the precautions you should take during the preparation of aspirin
suppositories by the molding method.
b) Why was the glycerol-gelatin base selected to prepare chlorhexidinie acetate
suppositories? Describe the precautions you should take.
c) What is the difference between the preparation method for traditional Chinese
medicine suppositories and suppositories containing chemical drugs?
References
[1] H. C. Ansel, N. G. Popovich and L. V. Allen, Jr. Pharmaceutical Dosage Forms and
Drug Delivery Systems, 8th ed., Williams and Wilkins, Baltimore, 2005.
[2] M.E. Aulton. Pharmaceutics: The science of dosage form design. 1988.
(Shirui MAO
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