Mechanism(s) of In Vitro Percutaneous Absorption Enhancement of Tamoxifen by Enhancers

Abstract The effects of enhancers (5% terpenes; i.e., eugenol, limonene, and menthone) in combination with 50% propylene glycol in water (50% PG) on the in vitro percutaneous absorption of tamoxifen through the porcine epidermis, on biophysical changes in the stratum corneum (SC) lipids, on macroscopic barrier properties, and on binding of the drug to the SC were investigated. These enhancers in combination with 50% PG significantly increased ( p p p in vitro transepidermal water loss (TEWL) in comparison with 50% PG alone. Thus, an enhancement by menthone, eugenol, and limonene in the permeability of the SC to tamoxifen is due to lipid extraction and macroscopic barrier perturbation. Moreover, the effective diffusion coefficient of tamoxifen through the epidermis was enhanced following the treatment with either 5% eugenol/50%PG or 5% limonene/50%PG compared with 50%PG alone. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 771–780, 2000