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 formulation on the skin. The studies were performed using in vitro diffusion cell techniques and a test formulation containing 2% 3H-minoxidil dissolved in 60% ethanol, 20% water and 20%¹⁴C-propylene glycol. The permeation of propylene glycol was effectively halted upon cleansing the skin surface; the skin had very little reservoir capacity for this substance. However, the rate of delivery of minoxidil was only slowed but not stopped upon cleansing. The suggestion here is that a reservoir of minoxidil is formed in the skin which is capable of sustaining an appreciable input of drug even after the skin’s surface is scrupulously cleaned. Assay of epidermal concentrations of these species not only confirms the existence of the minoxidil reservoir but also shows that the degree of its tissue concentration is proportional to the time of residence of the formulation on the skin surface. Reapplication of blank vehicle to the cleansed surface had little to no effect on the permeation of the minoxidil and was similarly without effect on that of propylene glycol. While it comes as no surprise that formulation residence time is an important variable in topical delivery, this study demonstrates the complexities of quantitative dependencies of delivery on residence time.