Effects of solvent deposited enhancers on transdermal permeation and their relationship with Emax

摘要

Many topical pharmaceuticals such as aerosols, topical sprays, and hydro-alcoholic and polymer based gels contain chemical enhancers. The objectives of the present study were to (a) determine the enhancement effects induced by enhancers deposited from a volatile solvent on human epidermal membrane (HEM) upon transdermal permeation enhancement, (b) compare these enhancement factors with Emax, and (c) examine the relationship between enhancer-induced permeation enhancement and stratum corneum equilibrium uptake enhancement. In this study, HEM was treated with enhancer/ethanol (enhancer dissolved in ethanol). After the evaporation of ethanol, passive transport experiments were conducted using corticosterone (G) as the model permeant. The uptake of another model corticosteroid, estradiol (E2 beta), into the intercellular lipid domain of stratum corneum after enhancer/ethanol treatment was also determined. The results show a correlation between Emax and the enhancement effect of most enhancers when the enhancers were deposited on the skin using the volatile solvent ethanol. The data suggest that the CS transport rate limiting domain was likely the same as the intercellular lipid domain probed by E2 beta uptake. The correlation between steady-state permeation enhancement and uptake enhancement into the intercellular lipid domain suggests that the permeation enhancement mechanism is primarily due to enhancement of permeant partitioning into the transport rate limiting domain.