Bioavailability assessment of topical delivery systems: Effect of vehicle evaporation upon in vitro delivery of minoxidil from solution formulations

Abstract

Two sets of in vitro permeation experiments were carried out to study the topical delivery of minoxidil as a function of its thermodynamic activity in the hydroalcoholic vehicles applied to the skin. Franz diffusion cells were employed with human cadaver skin membranes. The delivery of minoxidil of different concentrations (0.5%, 1%, 2%, 3%, 4% and 5%) from simple solutions in a fixed composition of propylene glycol/water/ethanol (20.0:63.2:16.8) was determined. The flux of minoxidil increased systematically from 0.5% to 3% concentration and then fell back abruptly at the 5% concentration. The maximum in the flux seen at the intermediate concentrations (3-4%) opened the possibility that the drug might be crystallizing upon evaporation of the volatile components of the vehicle. It was discovered that the 3% and even the 4% minoxidil concentration supported a relatively persistent supersaturation but at 5% the drug crystallized soon after its application. These phenomena were confirmed by observing crystal formation of minoxidil solutions under the microscope. It was found by following the weight of minoxidil solutions applied to a glass surface that 65% of the weight of the solution vehicle evaporated after the first 30 min and about 75% evaporated after 2 h. For the 5% minoxidil solution crystals were evident within 6-7 min. By way of contrast, no crystals were evident in the 3% minoxidil solution after 2 h. Secondly, since the evaporation of the volatile ethanol and water components of the vehicle play an important role in delivery permeation profiles of minoxidil (1%, 2%, 3% and 5%) from solutions of propylene glycol, water and ethanol prepared so as to contain a fixed amount of propylene glycol per unit weight of minoxidil were obtained. There was no significant difference in the flux of minoxidil when its concentration in the non-volatile component, propylene glycol, was kept constant.