TOPICAL DELIVERY SYSTEM FOR TRETINOIN - RESEARCH AND CLINICAL IMPLICATIONS

A novel topical tretinoin gel formulation containing a patented TopiCa re Delivery Compound, polyolprepolymer-2 (PP-2), was shown to signific antly reduce local irritation relative to a marketed tretinoin gel pre paration while maintaining clinical efficacy in the treatment of acne. Several in vitro percutaneous absorption studies were conducted with 0.025% tretinoin as a model compound to determine the possible mechani sm of action of PP-2 on drug delivery into and through human cadaver s kin. Results of these studies have repeatedly shown that a new topical gel formulation containing PP-2 significantly reduces tretinoin penet ration while potentially enhancing epidermal deposition compared with a commercial topical gel preparation at the same tretinoin concentrati on. These studies further support a mechanism of action whereby PP-2 s erves as a retentate for drug delivery by formation of a liquid reserv oir of polymer and solubilized drug on the skin surface and in the upp er layers of the skin, thereby modifying delivery of tretinoin into an d through skin. This reservoir of drug and polymer was established wit hin 15 min after topical application, and tretinoin was shown to be hi ghly associated with PP-2. These in vitro findings provide a model by which a new tretinoin gel formulation containing PP-2 reduces irritati on relative to a commercial tretinoin gel while maintaining clinical e fficacy in the treatment of acne vulgaris.