Effect of oleic acid ethanol and oleic acid propylene glycol on the in vitro percutaneous absorption of 5-fluorouracil and tamoxifen and the macroscopic barrier property of porcine epidermis

Transdermal delivery of most drugs is precluded due to the impervious nature of the stratum corneum. Chemical penetration enhancers offer an approach to enhance the transdermal transport of drugs by partitioning into and interacting with skin constituents, inducing a temporary reversible increase in skin permeability. The effect of penetration enhancers (e.g. oleic acid/ethanol and oleic acid/propylene glycol) was investigated on the in vitro percutaneous absorption of a hydrophilic (5-fluorouracil) and a lipophilic (tamoxifen) anticancer drug through porcine epidermis. In vitro transepidermal water loss (TEWL) studies were undertaken to investigate the effect of the above enhancers on the macroscopic barrier properties of the epidermis. Oleic acid/ethanol and oleic acid/propylene glycol significantly enhanced (P<0.05) the permeability coefficient of 5-fluorouracil (5-FU) and tamoxifen in comparison to their controls. In vitro TEWL was significantly greater (P < 0.01) through epidermis treated with the above enhancers in comparison with control (epidermis that was not treated). However, neither oleic acid/ethanol nor oleic acid/propylene glycol enhanced (P > 0.05) TEWL in comparison with ethanol and propylene glycol alone. Thus, changes in the permeability of 5-FU and tamoxifen caused by oleic acid/ethanol or oleic acid/propylene glycol could not be correlated with the in vitro TEWL. (C) 1998 Elsevier Science B.V. All rights reserved.