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 < 0.05) the permeability coefficient of tamoxifen in comparison with that of the control (50% PG in water). Fourier transform infrared spectroscopy (FT‐IR) was employed to investigate the biophysical changes in the SC lipids. The FT‐IR results showed that treatment of the SC with 5% terpenes/50% PG did not shift the asymmetric and symmetric C−H stretching absorbances peak positions to higher wavenumbers but resulted in a decrease in the peak heights and areas in comparison with the untreated SC. Treatment with menthone and limonene in combination with 50% PG significantly increased (p < 0.05) the partition coefficient of tamoxifen in comparison with treatment with 50% PG alone. Also, exposure of the SC to 5% terpenes in combination with 50% PG significantly increased (p < 0.05) the 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