Displacement Value
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
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