Skin permeation enhancement by n-decyl methyl sulfoxide: effect of solvent systems and insights on mechanism of action

Abstract

n-Decyl methyl sulfoxide (decy1MSO), was investigated for its permeation enhancement properties in aqueous and propylene glycol (PG) solutions in vitro through hairless mouse skin. 5-Fluorouracil (5-FU) and idoxuridine (IDU) were selected for this study because of their respective hydrophilic and hydrophobic characteristics. In aqueous solutions of decylMSO, a concentration-dependent enhancement was noted for both drugs. At a concentration of 1% decylMSO, 200- and 46-fold K p increases were found for 5-FU and IDU, respectively. On the other hand, in PG solutions practically no enhancement was observed except at high concentrations, where a relatively small increase in the permeability coefficient occurred. In these systems maximum enhancement was measured at a concentration of 15% decylMSO, where K p values increased for the respective drugs by only 7- and 10-fold. In contrast to decylMSO, Azone was very effective at increasing IDU permeation from PG solutions, even at concentrations as low as 0.5%; at 5% Azone, a maximum enhancement of 3 orders of magnitude was observed. These results point toward different mechanisms of action for Azone and decylMSO. DecylMSO activity in aqueous solutions may be related to its generation of micelles which solubilize lipophilic components in the skin, thus facilitating the transport of molecules. Lipophilic drugs may be entrapped in the surfactant micelles, leading to a decrease in drug availability.