DIFFERENCES IN PENETRATION-ENHANCING EFFECT OF AZONE THROUGH EXCISED RABBIT, RAT, HAIRLESS MOUSE, GUINEA-PIG AND HUMAN SKINS

The transdermal delivery of dihydroergotamine (DHE), from propylene gl ycol formulations with and without 6.0% laurocapram (Atone), and the p enetration enhancing effect of Atone were evaluated in vitro on excise d rabbit, rat, hairless mouse, guinea pig and human skins utilizing im proved Franz diffusion cells. The steady-state flux of DHE from the pr opylene glycol formulation without Atone were 0.045, 0.270, 0.395, 0.1 28 and 10.035 mu g/cm(2) per h across excised human, rat, guinea pig, rabbit and hairless mouse, respectively. Under the influence of the en hancer, Atone increased DHE penetration through excised skin of the va rious species used in this study in the following order: rabbit skin > human skin > rat skin > guinea pig skin > hairless mouse skin. The ma ximum enhancement factor of Atone (251.47) was obtained across rabbit skin and the minimum enhancing effect (14.44) was observed in the case of hairless mouse skin. The enhancement factor of Atone across human skin was 54.56. These results show that animal skins are poor models f or human skin under the conditions used. The lag time of DHE, from the propylene glycol formulation containing 6.0% Atone, through human ski n was longer than the lag limes across all other skin species tested i n this investigation.