Physicochemical study of percutaneous absorption enhancement by dimethyl sulfoxide: kinetic and thermodynamic determinants of dimethyl sulfoxide mediated mass transfer of alkanols.
By first determining the thermodynamic activities and activity coefficients of methanol, 1-butanol and 1-octanol in binary dimethyl sulfoxide:water media, it has been possible to separate solubilizing (thermodynamic) effects of dimethyl sulfoxide from its kinetic (diffusive) influence as they relate to the skin permeation of these small, nonelectrolyte alkanols. This was done by normalizing the experimental permeability coefficients found with full-thickness hairless mouse skin membranes to unit activity in the vehicle. When the dimethyl sulfoxide media were placed on both sides of the skin sections in a two compartment diffusion cell, activity-adjusted permeability coefficients of the permeants were invariant to dimethyl sulfoxide concentrations of 50% strength. Thus, up to this concentration and in the absence of net solvent crosscurrents, the permeabilities of methanol, 1-butanol, and 1-octanol appear to be strictly determined by partitioning into the stratum corneum. However, when the dimethyl sulfoxide percentage strength was raised to greater than or equal to 75%, activity-adjusted permeability increased systematically and profoundly, indicating severe barrier impairment with increased diffusion across the horny layer (kinetic effect). When neat dimethyl sulfoxide was placed on both sides of the skin, the experimental permeability coefficients of the three alcohols were maximal and equal in magnitude, suggesting total functional impairment of the stratum corneum. When the dimethyl sulfoxide media were placed in contact with the stratum corneum surface of the skin membranes only, accelerating effects were noted at dimethyl sulfoxide concentrations less than 50%, further supporting the idea that solvent cross flows themselves disrupt the horny structure. The degree of impairment was quantified under all experimental circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)
D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D013268:Stimulation, Chemical; D013816:Thermodynamics
D000438:Alcohols; D004121:Dimethyl Sulfoxide