TRANSDERMAL DELIVERY OF PHYSOSTIGMINE - A PRETREATMENT AGAINST ORGANOPHOSPHATE POISONING

Physostigmine absorption through isolated human skin and inhibition of plasma and red blood cell cholinesterases in guinea-pigs have been me asured to assess the feasibility of its transdermal delivery as a pret reatment for organophosphate poisoning. Penetration of radiolabelled p hysostigmine across human epidermis was measured in-vitro using glass diffusion cells and optimization of physostigmine delivery was achieve d by changes in vehicle formulation and use of penetration enhancers. Two-component vehicles consisting of propionic acid/isopropyl myristat e (50:50) and propionic acid/oleic acid (50:50) produced the highest t ransdermal delivery of physostigmine. A comparison of formulations con taining propionic acid alone with propionic acid plus oleic acid when applied to guinea-pigs, showed that inclusion of oleic acid allowed th e amount of physostigmine and the size of the transdermal patch to be substantially reduced, whilst maintaining effective delivery rates. Th e formulation containing oleic acid was not irritant to guinea-pigs wh en applied to the skin for 48 h. It is concluded that a mixture of pro pionic acid and oleic acid containing physostigmine is a good candidat e for transdermal delivery of physostigmine as a pretreatment for orga nophosphate poisoning.