Effects of penetration enhancers on in vitro percutaneous absorption of low molecular weight heparin through human skin
Xiong, G.L.; Quan, D.; Maibach, H.I.
Journal of Controlled Release 42(3): 289-296
The influence of the penetration enhancers, laurocapram (Azone), 1,8-cineole, and nerolidol on the in vitro percutaneous absorption of low molecular weight heparin (LMWH) through human skin was investigated. The enhancing effectiveness of the enhancers decreased in the order: laurocapram gt nerolidol gt 1,8-cineole. Compared to the control formulation without enhancers), a 4.4-fold enhancement was observed with 2% laurocapram and a 2-fold enhancement resulted with 2% nerolidol. There were no significant promoting effects at low concentrations of 1,8-cineole; however, a 3.5-fold increase in LMWH flux resulted with 10% 1,8-cineole. The highest enhancement factor was 5.6 with 5% laurocapram. Cellophane tape-stripping of the stratum corneum did not affect drug flux compared to the control (full-thickness skin). Thus the epidermis and dermis, as well as the stratum corneum, may constitute major rate determining barriers for LMWH permeation across human skin.