Displacement value & Specific problems in formulating suppositories – Pharmaceutics – I B. Pharma 1st Semester

Displacement Value

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

  1. Water in suppositories
  2. Hygroscopicity
  3. Incompatibilities
  4. Viscosity
  5. Brittleness
  6. Volume contraction
  7. Lubricants
  8. 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

Also, Visit:

B. Pharma Notes | B. Pharma Notes | Study material Bachelor of Pharmacy pdf

B. Pharma Handwritten Notes

B. Pharma PDF Books

B. Pharma Lab Manual

D. Pharma Lab Manual

B. Pharma 8th Semester Previous Year Question Paper

D. Pharma Notes

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