DIFFERENCES IN ENHANCING EFFECT OF 1-MENTHOL, ETHANOL AND THEIR COMBINATION BETWEEN HAIRLESS RAT AND HUMAN SKIN

The differences in skin permeation enhancing effect by 1-menthol, ethanol and their combination between hairless rat and human skin were investigated by measuring the permeation of isosorbide dinitrate (ISDN) as a model drug and all components in the donor vehicle through excised skin. Deuterium oxide (D2O) and ethanol-d(6) (EtOD) were used in place of water and ethanol, respectively. Vehicle compositions containing enhancers were 5% 1-menthol/D2O (MW), 40% EtOD/D2O (EW) and 5% 1-menthol/40% EtOD/D2O (MEW). D2O (W) was also used as a control vehicle. The permeability of each component (including ISDN) through human skin was lower than that through hairless rat skin in all the vehicles. A strong enhancement effect was achieved only by the combination of 1-menthol and ethanol (MEW) in human skin. The most marked difference in enhancing effect between hairless rat and human skin was observed with the application of MW. Comparison of the cumulative amount of each component between human and rat (human/rat) using MW showed 1-menthol to be 1/2, ISDN 1/8 and D2O 1/30. With MEW, on the other hand, human/rat ratios were similar (1-menthol, 1/3; ISDN, 1/3; EtOD, 1/3; D2O, 1/2) independent of the component species. In addition, there was a lag time of about 2 h for all components when MEW was applied to human skin, whereas no lag time was observed in hairless rat skin. Lipid leached from skin to the donor compartment was followed to evaluate the species difference. The results suggested that differences in lipid leaching between human and hairless rat skin might be one reason for the variation in enhancing effect or lag time.