EVALUATION OF DRUG PENETRATION INTO HUMAN SKIN EX-VIVO USING BRANCHEDFATTY-ACIDS AND PROPYLENE-GLYCOL

The influence of two middle chain methylbranched fatty acids and propy lene glycol on the penetration of the highly lipophilic model substanc e pyrene butyric acid into human skin ex vivo has been investigated. T he results obtained were compared with experimental data using oleic a cid as standard enhancer. Analogously, liberation studies of pyrene bu tyric acid into artificial lipid acceptor membranes were performed to evaluate the contribution of vehicle effects to the skin penetration r esults. It was shown that the fatty acids initially improve the libera tion of the model substance which corresponds to an increase in skin p enetration. When the penetration process was assessed, the dermal conc entration profiles of pyrene butyric acid and propylene glycol were al most the same, strongly indicating a cotransport for the lipophilic mo del substance. Levels of both pyrene butyric acid and propylene glycol did increase when the vehicles contained fatty acid. Furthermore, the re is some indication of a more specific action of oleic acid within t he stratum corneum. However, the major effect on the penetration of py rene butyric acid arises from propylene glycol. It is caused by solven t properties and solvent drag or favoured partition, respectively, int o the stratum corneum and the hydrophilic epidermis and dermis which a re supposed to be the main diffusion barrier for the model penetrant. Copyright (C) 1996 Elsevier Science B.V.