Physicochemical study of percutaneous absorption enhancement by dimethyl sulfoxide: dimethyl sulfoxide mediation of vidarabine (ara-A) permeation of hairless mouse skin

Abstract

Dimethyl sulfoxide's (DMSO) concentration-dependent influences on its own permeation rate through hairless mouse skin and on the concurrent permeation rates of water and the antiviral drug vidarabine (ara-A) have been studied at 37 degrees C using in vitro diffusion cells. Solubilities of ara-A in DMSO-water mixtures were also determined in order to assess ara-A's relative thermodynamic activity in the binary solvent media used in the mass transfer studies. Solubilities increased exponentially with increasing percentages of DMSO. Activity coefficients decreased accordingly. When the same DMSO medium was placed in each side of diffusion cell (balanced solvent configuration) permeability coefficients for ara-A decreased exactly as ara-A's solubility increased up to a 50% DMSO concentration, indicating the observed decreases in the mass transfer coefficients have thermodynamic origins. When DMSO media were placed in either the donor or receiver side of the cell up to the same 50% concentration point and opposed by a normal saline medium on the other side (asymmetric solvent configurations), the permeability of ara-A did not decrease and at some DMSO levels was substantially increased, behavior in marked departure from thermodynamic control. The behavior disparity between the 2 configurations of the cell suggests that cross-currents of solvents play a role in permeability enhancement. Regardless of solvent configuration, permeability coefficients for ara-A at 90 and 100% DMSO strengths were exaggeratedly large, consistent with severe impairment of the stratum corneum. Similar overall permeability behavior was observed for the 2 solvents, water and DMSO. Possible underlying mechanisms for these effects and the relative importance of the various mechanisms of DMSO enhancement as a function of DMSO's concentration and configuration are discussed.