Displacement
value
Contents
• Displacement
value
• Specific
problems in formulating suppositories
Learning objectives
At the end of this lecture, student will be
able to:
• Discuss
the importance of the displacement value
• Calculate
the displacement value
• Discuss
problems encountered during suppositories formulation and suggest remedies for
the same
•
Explain the importance of lubricants used for
suppository moulds
Displacement value
q The volume of a suppository from a
particular mould is uniform but its weight will vary because the densities of
medicaments usually differ from the density of the base.
q Hence it becomes necessary to calculate displacement value of
the base to be used for the particular medicament
Definition: The number of parts of medicament
(drug) that displaces one part by weight of the base is known as the
displacement value of that drug.
Calculation of Displacement
Value
Prepare and
weigh 10 suppositories containing base alone = [A] g
Prepare and weigh 10 suppositories containing
drug & base= [B]g
Total weight of the drug [C] = B-A g
Weight of the base displaced by [C] g of drug
= [D]
Displacement Value [D.V] = [C] / [D]
v Amount of the base displaced = Weight of the drug / Displacement value
Calculation for practical
purpose
To prepare and
submit 6 Boric acid suppositories (Calculate for 8)
Weight of boric acid for 1 suppository = 120mg
Weight of boric acid for 8 suppositories = 960mg
= 0.96g
Weight of cocoa butter for 1 suppository = 1g
Weight of cocoa butter for 8 suppositories = 8g
Displacement value of boric acid is 1.5 i.e., 1.5 g of boric
acid displaces 1 g of cocoa butter Therefore 0.96g of boric acid displaces =
0.96/1.5 = 0.64g of base
Therefore the total weight of cocoa butter required = 8 g –
0.64 g = 7.36 g
Lubrication of mould
q If the cavities are imperfect, i.e.
poorly polished or scratched, it may be difficult to remove the suppositories
without damaging their surfaces
q So lubrication of the moulds is
necessary
q In case of greasy or oily base water
soluble lubricants are required
q For water soluble /miscible bases
oily lubricant may be used
q For cocoa butter the following
lubricant solution formula may be used:
Soft soap –
10g
Glycerol –
10ml
Alcohol(90%) –
50ml
q For glycero-gelatin base, liquid
paraffin or arachis oil may be used as lubricant.
Specific problems in formulating suppositories
- Water
in suppositories - Hygroscopicity
- Incompatibilities
- Viscosity
- Brittleness
- Volume
contraction - Lubricants
- Rancidity
& oxidation
Water in suppositories
q Water
is used as a solvent to incorporate a water-soluble substance in the
suppository base. Incorporating water
should be avoided for the following reasons –
– Water
accelerates the oxidation of fats
– If
the water evaporates the dissolved substances crystallize out
– In
presence of water, reactions between various ingredients of suppositories may
occur
– The
water may be contaminated with bacteria or fungus
Hygroscopicity
q Glycerinated
gelatin suppositories lose moisture in dry climates and absorbs moisture in
high humidity
q Polyethylene
glycol bases are hygroscopic in nature
Incompatibilities
q Poyethylene
glycol (PEG) bases are incompatible with silver salts, tannic acid, quinine,
aspirin, benzocaine and sulfonamides.
q Many
chemicals have a tendency to crystallize out of PEG e.g. sodium barbital, salicylic acid and
camphor.
Viscosity
q Viscosity
of melted base is low in cocoa butter
q High
in PEG and glycerinated gelatin
q Low
viscosity base when melted the suspended particles may sediment very quickly
producing non-uniform distribution of drugs
Remedies for viscosity related problems
q The
base should be melted at the minimum temperature required to maintain the
fluidity of the base
q The
base is constantly stirred in such a way that the particles cannot settle and
no air is entrapped in the suppository.
q A
base with a narrow melting range closer to rectal temperature is used.
q Inclusion
of approximately 2% aluminium monostearate increase the viscosity of the fatty
base and also helps in homogeneous suspension of particles.
q Cetyl,
stearyl, myristyl alcohol or stearic acid are added to improve the consistency
of suppositories.
Brittleness
q Cocoa
butter base is not brittle but synthetic fat bases (with high degree of
hydrogenetation and high stearate containing bases) are brittle
q Brittle
suppositories produce trouble during manufacture, handling, packaging and
during use
q Causes:
Rapid chilling (shock cooling) of the melted bases in an extremely cold mould
Remedies for Brittleness
q The
temperature difference between the melted base and mould should be as small as
possible
q Addition
of small amount of Tween80, castor oil, glycerin or propylene glycol imparts
plasticity and make it less brittle
Volume contraction
q When
the bases are cooled in the mould volume of some bases may contract. Volume
contraction produces
– Good
release facilitating the ejecting from mold.
– Contraction
hole formation at the top.
– This
imperfection can be solved by adding slight excess base over the suppositories
and after cooled the excess is scrapped off.
Lubricants
q Cocoa
butter adheres to suppository molds because of very low volume of contraction
q Aqueous
lubricant may be used to remove the suppositories easily from the moulds
q They
are applied by wiping, brushing or spraying
q The
mould surfaces may be coated with teflon to reduce the adhesion of base to
mould wall
Rancidity & oxidation
Auto oxidation
•
Due to auto oxidation of unsaturated fatty acids
present in the base
Aldehydes ketones
•
saturated and unsaturated aldehydes, ketones and
acids may formed
Rancidification
•
Rancidity have very strong unpleasant odour
•
this
phenomenon is called rancidification
Antioxidants
q To
prevent this suitable antioxidants like
hydroquinione,
b-naphthoquinone,
a– and b-tocopherols,
gossypol
(present in cotton seed oil),
sesamol
(present in sesame oil)
propyl
gallate, gallic acid,
tannins
and tannic acids,
ascorbic
acid (Vit C.),
butylated
hydroxyanisole (BHA)
butylated
hydroxyanisole (BHA).
Summary
q The number of parts of medicament
(drug) that displaces one part by weight of the base is known as the
displacement value of that drug.
v Amount of the base displaced = Weight of the drug / Displacement value