INFLUENCE OF APPLICATION TIME AND FORMULATION REAPPLICATION ON THE DELIVERY OF MINOXIDIL THROUGH HAIRLESS MOUSE SKIN AS MEASURED IN FRANZ DIFFUSION CELLS

Relationships are drawn between the extent of topical delivery of test compounds in solution and the period of residence of their formulatio n on the skin. The studies were performed using in vitro diffusion cel l techniques and a test formulation containing 2% H-3-minoxidil dissol ved in 60% ethanol, 20% water and 20% C-14-propylene glycol. The perme ation of propylene glycol was effectively halted upon cleansing the sk in surface; the skin had very little reservoir capacity for this subst ance. However, the rate of delivery of minoxidil was only slowed but n ot stopped upon cleansing. The suggestion here is that a reservoir of minoxidil is formed in the skin which is capable of sustaining an appr eciable input of drug even after the skin's surface is scrupulously cl eaned. Assay of epidermal concentrations of these species not only con firms the existence of the minoxidil reservoir but also shows that the degree of its tissue concentration is proportional to the time of res idence of the formulation on the skin surface. Reapplication of blank vehicle to the cleansed surface had little to no effect on the permeat ion of the minoxidil and was similarly without effect on that of propy lene glycol. While it comes as no surprise that formulation residence time is an important variable in topical delivery, this study demonstr ates the complexities of quantitative dependencies of delivery on resi dence time.