TRANSDERMAL ABSORPTION OF STEROIDS

The transport mechanisms of selected steroids in the presence of a ser ies of aqueous ethanol solutions have been probed in vitro using hairl ess mouse and human tissue, as well as in vivo using the unique human skin sandwich flap model. Permeation and biophysical studies have also been performed under similar conditions in order to elucidate the bio physical alterations in hairless mouse and human stratum corneum induc ed by the vehicle solutions that contribute to the percutaneous transp ort mechanisms of steroids. Progesterone, estradiol and hydrocortisone transport across hairless mouse skin under the same conditions was ex amined to explore the effects of permeant properties. Steroid uptake a nd in vitro permeability coefficients across both skin species decreas ed with decreasing steroid lipophilicity. The polar character of the s teroids influences not only partitioning, but also the effective diffu sivity in the stratum corneum, as suggested from permeability coeffici ents calculated with a mathematical model. As steroids become more pol ar, the effective diffusivities decrease and the degree to which the s tratum corneum controls overall diffusion increases. Estradiol permeab ility coefficients in vivo with the human skin sandwich flap were 10-f old higher than with human epidermis in vitro. Estradiol uptake and pe rmeability coefficients decreased with the presence of increasing etha nol concentrations. Similarities in estradiol permeation in vitro thro ugh hairless mouse skin and human epidermis were further reflected in similarities of the human and hairless mouse stratum corneum lipid dom ain biophysical structures.