Stereoselective Permeation of Tretinoin and Isotretinoin through Enhancer-Treated Rat Skin. I. Effect of Ethanol and Sodium Dodecyl Sulfate

Abstract

Many properties of chemicals depend on their streochemistry. Among these, the effects of streoisomerism on percutaneous absorption of drugs, which is subject of the present investigation, is not well studied yet. In this study, tretinoin (TT) and isotretinoin (ITT) (geometric isomers) were chosen and their permeations (alone or in the presence of each other) through enhancer-treated excised rat skin were studied. These studies employed static diffusion cells, saturated solution of drugs in water:propylene glycol system as the donor phase and aqueous solution of Tween20 as the receptor phase. Aqueous solutions of sodium dodecyl sulfate (SDS) (2, 4, 6 and 8%, w/v) and ethanol (EtOH) (25, 50, 75 and 96%, v/v) were used as enhancers. Results showed that TT permeates SDS-treated skin by about 1.6-1.8 times faster than ITT (P<0.0001). Permeability coefficient (Kp) of TT through SDS-treated skin was also 1.1-1.3 times more than that of ITT (P<0.004). In ethanol-treated systems, while the flux of TT was significantly (P<0.0003) more than that of ITT (by about 1.4-1.7 times) for all ethanol concentrations, there was no difference between Kp of TT and ITT in 25 and 50% ethanoltreated systems. At higher ethanol concentrations, Kp of TT was significantly (P<0.046) more than that of ITT. When the retinoids were used together, flux ratios (TT/ITT) were almost twice of those observed in single-retinoid application studies. These data show that the isomers might affect permeation of each other, which might be due to competition of isomers for permeation through the skin. The present results clearly show that permeation of these isomers through enhancer-treated rat skin is stereoselective, and that the level of stereoselectivity depends on enhancer type and concentration.