title: Transdermal delivery of physostigmine. A pretreatment against organophosphate poisoning.
abstract: Physostigmine absorption through isolated human skin and inhibition of plasma and red blood cell cholinesterases in guinea-pigs have been measured to assess the feasibility of its transdermal delivery as a pretreatment for organophosphate poisoning. Penetration of radiolabelled physostigmine across human epidermis was measured in-vitro using glass diffusion cells and optimization of physostigmine delivery was achieved by changes in vehicle formulation and use of penetration enhancers. Two-component vehicles consisting of propionic acid/isopropyl myristate (50:50) and propionic acid/oleic acid (50:50) produced the highest transdermal delivery of physostigmine. A comparison of formulations containing propionic acid alone with propionic acid plus oleic acid when applied to guinea-pigs, showed that inclusion of oleic acid allowed the amount of physostigmine and the size of the transdermal patch to be substantially reduced, whilst maintaining effective delivery rates. The formulation containing oleic acid was not irritant to guinea-pigs when applied to the skin for 48 h. It is concluded that a mixture of propionic acid and oleic acid containing physostigmine is a good candidate for transdermal delivery of physostigmine as a pretreatment for organophosphate poisoning.
authors.affiliation: Biology Division, Chemical and Biological Defence Establishment, Salisbury, Wiltshire, UK.
authors.forename: J
authors.initials: J
authors.lastname: Jenner
authors.forename: A
authors.initials: A
authors.lastname: Saleem
authors.forename: D
authors.initials: D
authors.lastname: Swanston
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000506:poisoning*; D008297:Male; D009226:Myristates / Q000737:chemistry; D019301:Oleic Acid; D009829:Oleic Acids / Q000737:chemistry; D009943:Organophosphorus Compounds; D010830:Physostigmine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011041:Poisoning / Q000517:prevention & control; D011422:Propionates / Q000737:chemistry; D012044:Regression Analysis; D012869:Skin Absorption
chemical_list: D007306:Insecticides; D009226:Myristates; D009829:Oleic Acids; D009943:Organophosphorus Compounds; D011422:Propionates; C008205:isopropyl myristate; D019301:Oleic Acid; D010830:Physostigmine; C029658:propionic acid