Effect of dimethyl sulfoxide on drug permeation through human skin

Abstract

Abstract The effect of the presence of dimethyl sulfoxide (in admixture with water) on the sorption and permeation rate of scopolamine base in human skin in vitro has been measured as a function of drug concentration in aqueous solution. The equilibrium sorption of scopolamine by skin from solution appears to be unaffected by the presence of even high concentrations of dimethyl sulfoxide in the solution phase. In the absence of a transdermal gradient of DMSO (or water), the permeability of skin to scopolamine in the presence of DMSO is about twofold higher than in its absence, suggesting that the diffusivity of scopolamine in the stratum corneum is somewhat elevated by the solvating action of DMSO. When, however, a gradient of DMSO concentration is impressed across the skin (irrespective of whether that gradient is of the same or opposite sign to that of the drug), the permeability of the skin to scopolamine is increased by one to two orders of magnitude. Microscopic examination of the skin subjected to such treatment reveals marked swelling, distortion, and intercellular delamination of the stratum corneum, which is only partially reversible following complete extraction with water. These effects are believed due to development of very high osmotic stresses produced within the stratum corneum, as both water and DMSO are transported into the tissue.