Effect of minoxidil concentration on the deposition of drug and vehicle into the skin

Minoxidil dissolved in propylene glycol/ethanol/water (20: 60: 20; v/v) was more efficiently delivered into hairless mouse skin from a 0.02% solution than from a 2% formulation during in vitro mass balance experiments. Evaporation of the vehicle after application of the 2% minoxidil solution led to compositional changes so drastic that saturation is attained quickly. The shifting compositions of the vehicle were experimentally profiled and the drug’s solubility was measured in media reflecting these changes over time. The original 2% formulation has excess capacity to dissolve minoxidil but, following its application, the solution rapidly saturates through evaporation, reaching saturation within 30 minutes. While the 2% formulation definitely functions at a proportionally higher thermodynamic activity than the 0.02% formulation at early times, most of this thermodynamic advantage is lost abruptly upon precipitation of the drug. The driving force following drug precipitation only reflects the dissolved minoxidil, and thus the relative delivery rate of the 2% formulation eventually drops to only several multiples of the delivery rate of the 0.02% solution which never quite attains saturation.