Submicron oil-in-water emulsion formulations for mefloquine and halofantrine: Effect of electric-charge inducers on antimalarial activity in mice

Stearylamine, oleic acid, phosphatidylserine and dicetylphosphate have been studied to determine their capacity to induce electric charge on non-ionic submicron emulsions containing halofantrine and mefloquine. The in-vivo antimalarial activity of drug-loaded emulsions, evaluated in mi ce, was affected by the nature of the additives used. In particular, the el ectric-charge inducers markedly affected the pharmacological activity of me floquine, but not of halofantrine. After subcutaneous administration ED50 v alues (the doses affording 50% protection) were 3 and 15 mg kg(-1), respect ively, for halofantrine and mefloquine emulsions without charge inducers. T he mefloquine-loaded emulsions with charge inducers were active at 10 mg kg (-1) for dicetylphosphate, 17 mg kg(-1) for phosphatidylserine, 23 mg kg(-1 ) for oleic acid and 27 mg kg(-1) for stearylamine, again after subcutaneou s administration. This work has enabled the formulation of stable emulsions, incorporating dr ugs with high antimalarial activity, which are proposed for parenteral deli very of these fairly soluble drugs.