PROCEDURE FOR THE EVALUATION OF THE BIOAVAILABILITY OF TOPICAL FORMULATIONS IN-VIVO AS THE RATE AND EXTENT TO WHICH THE ACTIVE-DRUG PRODUCTIS TRANSFERRED FROM THE VEHICLE TO THE SKIN

A procedure was developed for the in vivo evaluation of the bioavailab ility of topical formulations containing a limited amount of the activ e drug product estimated as the rate and extent to which the drug is r eleased from the vehicle to the skin. It is assumed that drug transfer follows Fick's law of diffusion. The formulation rested was a cream c ontaining 40 mu mol/ml (20 mg/ml) of sertaconazole, a novel imidazole antifungal agent, applied to healthy volunteers. Eight 9 cm(2) squares were marked in the volar forearm surface and 0.1 ml of the cream was applied to each square by gentle rubbing with a plastic thimble. The a ctually applied dose was estimated considering the drug amount that ad hered to the thimble. Then one area at a time was cleansed at 0, 1, 2, 4, 6, 8, 12, and 24 h and the amount of sertaconazole transferred to the skin was estimated by determination of the amount of drug removed by cleansing. Drug release from the vehicle to the skin increased with time, but then reached a plateau. The maximal amount of drug transfer red to the skin was 85.5 +/- 3.3% (mean +/- S.D.) of the actually appl ied dose, and this value was considered an expression of the extent of drug release. The rate of release was estimated as the half-life of t he transfer process, which was 1.83 +/- 0.76 h. This procedure is suit able for the evaluation of topical formulations containing a limited a mount of the active drug product. (C) 1995 Wiley-Liss, Inc.