TOPICAL DELIVERY OF KELOID THERAPEUTIC DRUG, TRANILAST, BY COMBINED USE OF OLEIC-ACID AND PROPYLENE-GLYCOL AS A PENETRATION ENHANCER - EVALUATION BY SKIN MICRODIALYSIS IN RATS

Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic aci d), an inhibitor of collagen synthesis and a therapeutic drug for kelo id and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration en hancer. Evaluation was by measurement of the concentration of tranilas t in plasma and in the dialysate from skin microdialysis. When tranila st at a dose of 1.5 mg was applied topically as an ethanol solution co ntaining 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm(2)) , the maximum concentration of tranilast in skin dialysate was approxi mately 2 mu M. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate incr eased to 10-20 mu M, and this value was further increased to 60 mu M b y the addition of a combination of oleic acid (10 or 20%) and, propyle ne glycol (10%) to the solution. With the combination of oleic acid an d propylene glycol the area under the plot of the concentration of tra nilast in skin dialysate against time between 0 and 4 h (AUC(0-4)) was more than 400-fold that after intravenous administration. The transde rmal bioavailability of tranilast as assessed by the AUC(0-4) of trani last in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, an d 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical del ivery of tranilast with an absorption enhancer such as a mixture of ol eic acid and propylene glycol might be a more effective medication tha n oral administration of tranilast fbr the treatment of keloid and hyp ertrophic scar.