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% s olution than from a 2% formulation during in vitro mass balance experi ments. Evaporation of the vehicle after application of the 2% minoxidi l solution led to compositional changes so drastic that saturation is attained quickly. The shifting compositions of the vehicle were experi mentally profiled and the drug's solubility was measured in media refl ecting these changes over time. The original 2% formulation has excess capacity to dissolve minoxidil but, following its application, the so lution rapidly saturates through evaporation, reaching saturation with in 30 minutes. While the 2% formulation definitely functions at a prop ortionally higher thermodynamic activity than the 0.02% formulation at early times, most of this thermodynamic advantage is lost abruptly up on precipitation of the drug. The driving force following drug precipi tation only reflects the dissolved minoxidil, and thus the relative de livery rate of the 2% formulation eventually drops to only several mul tiples of the delivery rate of the 0.02% solution which never quite at tains saturation.