Percutaneous absorption of retinoids: influence of vehicle, light exposure, and dose

Abstract

The percutaneous absorption characteristics of isotretinoin, etretinate, tretinoin, and acitretin were investigated in vitro to assess the feasibility of their topical application for dermatological disorders. The influence of vehicle, photodegradation, and dose was examined. Retinoid absorption through monkey skin was highly vehicle dependent and followed the order: propylene glycol = isopropyl alcohol greater than mineral oil greater than diisopropyl adipate greater than polyethylene glycol 400. Peak flux of etretinate (an ester) was less than 50% that of the acid retinoids in both human and monkey skin. Exposure to light caused a 60% degradation of isotretinoin on the surface of the skin, but did not change the amount of drug which penetrated the epidermis. In accord with this result, the amount of isotretinoin and acitretin which penetrated epidermis did not increase in proportion to dose over a 25-fold range of dose in human skin. Dermal concentration at doses of 10 micrograms/cm2 of isotretinoin and acitretin were greater than that reported for shave biopsies of human skin following treatment for several months with clinically effective doses of isotretinoin and etretinate (the parent ester of the acid acitretin).