Bioavailability assessment of topical delivery systems: in vitro delivery of minoxidil from prototypical semi-solid formulations

Abstract

An in vitro technique has been developed for evaluating the delivery performance of topical semi-solid formulations. A thin and uniform layer of formulation was applied in facsimile to actual usage conditions by troweling the vehicle across a thin. circular copper template (200 μm in thickness). Approximately 30–45 mg of an oil-in-water cream, a water-in-oil cream or an ointment, each containing a range of concentrations of minoxidil, were applied over human cadaver skin within a defined circular area of 1.54 cm 2. The rates of permeation of minoxidil from these formulations were determined by finite dose diffusion experiments. For formulations containing 2% minoxidil, the flux from the w/o cream tested was about 4 times higher than fluxes from the o/w cream and the ointment. Even though all w/o formulations were initially saturated with drug, the flux of minoxidil from these creams increased as the concentration of minoxidil was increased from 0.5% to 2%. In contrast, the delivery rates from the o/w cream and the ointment did not appear to be dependent on the minoxidil concentration applied (0.5–2%). Under the operative experimental conditions, the percent coefficients of variation of flux of minoxidil from these formulations were less than 20%. To achieve this low level of variability, the skin samples were all obtained from the same cadaver abdomen. If one assumes that the efficacy of a particular formulation is dependent on the ability of the drug to be released from the vehicle and diffuse through the skin, the studies show that the nature of the vehicle can profoundly affect delivery even when excess solid drug is present. They also indicate that reliable in vitro comparisons of drug delivery are possible as long as one performs the studies on skin samples taken from the same section of skin.