Effect of pH on skin permeation enhancement of acidic drugs by 1-menthol-ethanol system

The effect of pH on the skin permeation enhancement of three acidic drugs b y the 1-menthol-ethanol system was investigated. The total flux of acidic d rugs from the system remarkably varied over the pH range 3.0-8.0, and the p ermeation enhancement factor depended on the system pH and drug. A skin per meation model, which consists of two permeant (unionized and ionized) speci es, two system (oily and aqueous) phases, and two permeation (lipid and por e) pathways, was developed. The assumptions were made that only the unioniz ed species can distribute to the oily phase and transport via the lipid pat hway. The model explained the relationship between the concentration of dru g in the aqueous phase and system pH. The skin permeability data were also described by the model and permeability coefficients corresponding to the p hysicochemical properties of permeant were calculated for the lipid and por e pathways. The model simulation showed that the permeation of acidic drugs : occurred from the aqueous phase and the oily phase acted as a reservoir. Whether the total flux increased with increase of pH was dependent on the l ipophilicity of drug. These results suggest that the pH of 1-menthol-ethano l system should be given attention to elicit the maximum permeation enhance ment. (C) 2001 Elsevier Science B.V. All rights reserved.