Kinetics of transdermal drug permeation and mechanisms of skin permeation enhancement.

摘要

The present research work was designed to investigate: (1) the skin permeation of progestins and the effects of skin strippings, vehicle, temperature, and skin permeation enhancers; (2) the mechanisms of enhancement in skin permeation as the result in the use of skin permeation enhancers.; The abdominal skin of hairless mouse was used in the in vitro study. Progesterone and its hydroxylated derivatives, having hydroxy group(s) substituted at different position(s), were utilized as permeants to evaluate the structure-permeability relationship. Azone (1-dodecylazacycloheptan-2-one), decylmethyl sulfoxide, capryl alcohol and ethyl caprylate were used as skin permeation enhancers to investigate their ability in enhancing the skin permeation of progesterone and its hydroxylated derivatives and to investigate the mechanisms of enhancement.; The percutaneous absorption of progestins was examined by applying bi-layer skin model. The reservoir capacity of stratum corneum was evaluated, both experimentally and mathematically, by dual desorption model. The thermodynamics for the skin permeation of progestins was studied by applying Arrhenius equation. The mechanisms of enhancement in skin permeation by azone were investigated by evaluating the changes in the diffusivity and solubility of the progestins in each skin layer as a function of azone concentrations. By studying the permeation through the delipidized skin and the effect of azone, it was found that the permeation of progesterone and hydrocortisone through the delipidized skin was less enhanced than that through intact skin. This result further substantiated that the mechanism of enhancement for azone is related to its action on the permeation of permeants through the lipid matrix pathway.