Effect of skin surface temperature on transdermal absorption of flurbiprofen from a cataplasm.

Abstract

Transdermal absorption of flurbiprofen (FP) from a cataplasm (CFP) and its antiinflammatory effect were investigated in the rat under various skin temperature conditions. As the skin temperature was raised, the plasma concentration of FP after application of the cataplasm increased significantly. It was demonstrated by a release and in vitro penetration experiment that skin penetration is the rate-determining step for absorption, and both release and penetration increased with a rise of temperature. Moreover, the in vivo transdermal absorption behavior was estimated by a deconvolution method from the plasma concentration data after intravenous administration and topical application of FP.The Arrhenius plot of the in vitro penetration data at various temperature gave a nearly straight line and the activation energy calculated from the slope was 16.7 kcal/mol. The skin accumulation of FP decreased with a rise of temperature in the in vivo experiment while no significant change was seen in the in vitro experiment, suggesting participation of the increase of blood flow in the former experiment.Though the anti-inflammatory effect was demonstrated at the normal skin temperature and under cooling, the effect was not found under warming. In addition, a considerable effect was observed with a control CFP which is free from FP when used under cooling.From these results, it is suggested that the transdermal absorption of FP from CFP increased with a rise of skin surface temperature, and both factors, the concentration of FP absorbed and topical cooling, contribute to the anti-inflammatory effect.