EFFECTS OF PENETRATION ENHANCERS ON IN-VITRO PERCUTANEOUS-ABSORPTION OF LOW-MOLECULAR-WEIGHT HEPARIN THROUGH HUMAN SKIN

The influence of the penetration enhancers, laurocapram (Azone(R)), 1, 8-cineole, and nerolidol on the in vitro percutaneous absorption of lo w molecular weight heparin (LMWH) through human skin was investigated. The enhancing effectiveness of the enhancers decreased in the order: laurocapram > nerolidol > 1,8-cineole. Compared to the control formula tion (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-ci neole; 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 f lux 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.