Permeability of benzoic acid derivatives in excised guinea pig dorsal skin and effects of L-menthol

Penetration through excised guinea pig dorsal skin was examined for nine mono-substituents of benzoic acid derivatives. Permeability coefficients of the derivatives correlated well with their n-octanol/water partition coefficients. Since the regression coefficient was similar to the value obtained in human skin, it is suggested that the lipid lamellae of guinea pig skin resembled that of human skin in lipophilicity. Addition of penetration enhancer; 1% L-menthol in 15% ethanol markedly increased the flux and permeability coefficients of relatively hydrophilic derivatives and decreased the dependency of the permeability coefficients on the partition coefficients. Electron spin resonance analysis using 5-doxylstearic acid revealed the presence of a strongly immobilized component of the spin label in the skin and its disappearance in the presence of 1% L-menthol in 15% ethanol. These results suggest that the rigid lamellar structure of the stratum corneum was disrupted by L-menthol with ethanol, and caused the enhancement of penetration of relatively hydrophilic benzoic acid derivatives. (C) 1998 Elsevier Science B.V.