Effects of isopropanol-isopropyl myristate binary enhancers on in vitro transport of estradiol in human epidermis: a mechanistic evaluation.
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.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA. pliu@biodel.com
Puchun
P
Liu
Melinda
M
Cettina
Judy
J
Wong
D019840:2-Propanol / Q000494:pharmacology*; D002102:Cadaver; D004058:Diffusion; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009226:Myristates / Q000494:pharmacology*; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013816:Thermodynamics
D009226:Myristates; C008205:isopropyl myristate; D004958:Estradiol; D019840:2-Propanol