Pharmacological evaluation of an injectable prolonged release emulsion of physostigmine in rabbits

Abstract

Physostigmine was incorporated in an injectable emulsion in an attempt to prolong its pharmacological activity. Emulsions which remained stable over 6 month storage were prepared using optimal experimental conditions. The in-vitro kinetic examination revealed that the rate-determining step in the release process of physostigmine from the emulsion was its partitioning from the oily phase to the external aqueous phase. The in-vivo results indicated that the physostigmine emulsion was able to inhibit the cholinesterase activity for at least 4 h, while the conventional injection inhibited the cholinesterase activity for only 1 to 2 h. The preliminary pharmacokinetic analysis showed that the physostigmine emulsion apparently increased the bioavailability compared with the conventional injectable solution. This could be attributed either to the protection of the sensitive drug from the enzymatic degradation or to improved absorption. The presence of poloxamer micelles in the aqueous phase was shown to enhance the bioavailability of physostigmine without having any effect on its pharmacological activity or duration.