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The mechanism of l-menthol, oleic acid and lauricidin as enhancers on percutaneous absorption was examined using diclofenac (DH) as a hydrophobic drug and sodium diclofenac (DNa) as a hydrophilic drug in in vitro diffusion experiments with two kinds of membranes: ethanol-treated and untreated silicone membranes; these were models for the lipid and pore pathways of skin. A 20% w/w ethanol-aqueous solution decreased the flux of DH but increased the flux of DNa significantly across the treated membrane compared with those fluxes across the untreated membrane, suggesting that DH penetrated by the lipid pathway and DNa by the pore pathway. The permeability of DNa through the pore pathway decreased significantly across the treated membrane with the addition of oleic acid and lauricidin. l-Menthol increased the permeability coefficients of DH and DNa more in a treated membrane than in an untreated one, showing the same tendency as in rat skin. Thus, while oleic acid and lauricidin did not increase the permeation of DNa by the pore pathway, l-menthol appeared to enhance the permeation of the drug by both the lipid and pore pathways.

chemical and pharmaceutical bulletin/chemical and pharmaceutical bulletin

l-Menthol, Oleic Acid and Lauricidin in Absorption Enhancement of Free and Sodium Salt of Diclofenac Using Ethanol Treated Silicone Membrane as Model for Skin.