Abstract Antimony-containing anti-leishmaniasis drugs are encapsulated in a lipid based liposomal formulation having a weight ratio of lipid to encapsulated antimony-containing drug of 1:1.6 to 1:0.25 and a salt concentration in the continuous aqueous phase which is at least isotonic with human blood. Such formulations are found to have a leakage rate of initially encapsulated antimony-containing drug of less than 50% by weight after storage at 25° C. for 6 weeks from encapsulation and hence provide storage stable formulations which can be used effectively after prolonged storage without refrigeration in tropical climates. The anti-parasital activity of the liposomal formulations has been found greater than that of corresponding aqueous formulations. The liposomal formulations are preferably prepared by a reverse phase evaporation method involving first emulsifying an aqueous solution of the drug with an organic solvent solution of the lipid and then removing the organic solvent at reduced pressure at a temperature below the normal boiling point of the solvent but above the phase transition temperature of the lipid.
A pharmaceutical formulation consisting essentially of an anti-leishmanial effective amount of sodium stibogluconate encapsulated in liposomes consisting of dipalmitoylphosphatidyl choline, cholesterol and dicetyl phosphate in a molar ratio of 4.5:4.5:1 respectively, the weight ratio of the lipid mixture to encapsulated said sodium stibogluconate being from 1:1.6 to 1:0.25 said liposomes being suspended in a continuous aqueous phase containing a pharmaceutically acceptable salt and having a tonicity at least twice that of human blood and having a pH of about 5.5 to 7 whereby the leakage rate of initially encapsulated sodium stibogluconate is less than 50% by weight after storage at 25° C. for 6 weeks from encapsulation.
Claim 2
Dependent Claim
107 words
A pharmaceutical formulation consisting essentially of an anti-leishmanial effective amount of sodium stibogluconate encapsulated in liposomes consisting of dipalmitoylphosphatidyl choline, cholesterol and dicetyl phosphate in a molar ratio of 4.5:4.5:1 respectively, the weight ratio of the lipid mixture to encapsulated said sodium stibogluconate being from 1:1.6 to 1:0.25 said liposomes being suspended in a continuous aqueous phase containing a pharmaceutically acceptable salt and having a tonicity at least twice that of human blood and having a pH of about 5.5 to 7 whereby the leakage rate of initially encapsulated sodium stibogluconate is less than 50% by weight after storage at 25° C. for 6 weeks from encapsulation.
Claim 3
Dependent Claim
17 words
A formulation according to claim 1 wherein the lipid mixture:encapsulated drug weight ratio is 1:1.5 to 1:0.5.
Claim 4
Dependent Claim
18 words
A formulation according to claim 1 wherein the diameter of the liposomes is about 0.9 to 2.3 μm.
Claim 5
Dependent Claim
35 words
A formulation according to claim 1 wherein said pharmaceutically acceptable salt is sodium chloride present in a concentration such that the tonicity of the continuous aqueous phase is at least twice that of human blood.