Enhanced in vitro skin permeation of cationic drugs

The lipophilicity of cationic drugs can be increased by forming ion pairs with the carboxylate anion of fatty acids. Transport of cations across an isopropyl myristate (IPM) membrane was facilitated in the presence of oleic acid and lauric acid, providing an appropriate pH gradient existed. Enhancement of in vitro skin permeation of various drugs, in the presence of fatty acids, was shown to be more dramatic with the slow-permeating neutral caffeine and anionic salicylate. Since both molecules are unable to form ion pairs it is probable that the fatty acids are capable of exerting a disruptive influence on the skin. The cationic drugs appeared to traverse excised human skin more rapidly than predicted by the model membrane data. This may be due to ion pairing with free fatty acids or other anionic groups within the skin. Consequently, the enhancing ability of fatty acids was less marked for neutral or anionic permeants.