Relationship between the enhancement effects of chemical permeation enhancers on the lipoidal transport pathway across human skin under the symmetric and asymmetric conditions in vitro.

PURPOSE: Previously, the mechanisms of action of chemical permeation enhancers (CPEs) were studied, and a quantitative structure-enhancement relationship for the lipoidal transport pathway of the stratum corneum was established under symmetric and equilibrium conditions. The present study examined whether the effects of CPEs under the asymmetric conditions could be predicted by those determined using the symmetric transport experimental approach.

METHODS

Both symmetric (same CPE concentration in both donor and receiver chambers) and asymmetric (CPE in the donor chamber only and phosphate-buffered saline solution in the receiver) transport experiments were carried out in a two-chamber side-by-side diffusion cell with human epidermal membrane (HEM). Corticosterone was the model permeant to probe the effects of CPEs upon the HEM lipoidal pathway under these conditions.

RESULTS

A correlation between the experimental enhancement factors under the asymmetric conditions (E (Asym)) and those under the symmetric conditions (E (Sym)) was observed. The potencies of CPEs based on their donor concentrations are related to their lipophilicities.

CONCLUSIONS

The results suggest that the symmetric configuration findings in the previous studies can be used to explain the effects of CPEs under the asymmetric condition likely encountered in practice and to understand drug delivery enhancement in transdermal enhancer formulation development.