1998 Volume 58 Issue 1 Pages 10-16
The purpose of this study is to determine a specific enhancer to increase the skin permeation of only lipophilic or hydrophilic drugs. Seven kinds of enhancers were evaluated about the specificity or selectivity of their skin permeation-enhancing effects by an in vitro permeation study using 2-chamber diffusion cells and excised hairless rat skin. Isosorbide dinitrate and antipyrine were used as models for typical lipophilic and hydrophilic drugs. The enhancement factors were calculated by dividing the obtained steady-state flux of the drugs with each enhancer by that without enhancer (control), and the specificity of the enhancers was evaluated using these factors. As a result, the effect of each enhancer was greatly related to the lipophilicity of the drugs. The enhancers were therefore divided by the values of the factors into type 1 enhancers, which specially increased the skin permeation of the lipophilic drug isosorbide dinitrate such as lauric acid and lauryl alcohol; type 2 enhancers, which promoted the permeation of the hydrophilic drug antipyrine such as α-terpineol, l-menthol and N-methyl-2-pyrrolidone; and type 3 enhancers, which enhanced the permeation of both drugs such as isopropyl myristate and Azone®. The difference in the specificity in the enhancing effects might be the result of the skin permeation-enhancing mechanism. The mechanism may be related to structural properties of the enhancers rather than their physicochemical characteristics.
