Effects of Isopropanol–Isopropyl Myristate Binary Enhancers on In Vitro Transport of Estradiol in Human Epidermis: A Mechanistic Evaluation

Abstract

The purpose of this study was to mechanistically investigate effects of isopropanol (IPA)–isopropyl myristate (IPM) binary enhancers on transport of a model drug, estradiol (E2) in human epidermis (stratum corneum + viable epidermis) in vitro. The study was focused on use of the same IPA–IPM compositions on both sides of the skin (“symmetric” configuration) with saturated E2 (maximum thermodynamic activity). For E2 transport in all IPA–IPM compositions tested, stratum corneum still was the rate‐limiting layer of human epidermis. The relative contributions to E2 flux enhancement were separated into the changes in solubility and diffusivity of E2 in stratum corneum. As a major factor, E2 solubility in stratum corneum was enhanced by 35 times with increasing IPA from neat IPM to neat IPA. E2 diffusivity in stratum corneum also played a significant role, which increased by 8 times from neat IPM to 50% IPA. Stratum corneum swelled more in IPM‐rich region, decreased with increasing IPA, and even deswelled in neat IPA. IPA uptake correlated well to E2 solubility in stratum corneum; both linearly increased with increasing IPA. IPM uptake appeared to correlate to E2 diffusivity in stratum corneum; both maximized around 50% IPA. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:565–572, 2009