Topical Delivery System for Tretinoin: Research and Clinical Implications

• Published in: Journal of pharmaceutical sciences Vol. 86; no. 10; pp. 1138 - 1143
• Main Authors: Skov, Michael J., Quigley, John W., Bucks, Daniel A.W.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.10.1997; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Administration, Topical; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Drug Delivery Systems; Drug Interactions; Gels; Humans; In Vitro Techniques; Keratolytic Agents - administration & dosage; Keratolytic Agents - pharmacokinetics; Medical sciences; Pharmacology. Drug treatments; Polypropylenes - administration & dosage; Polyurethanes - administration & dosage; Skin Absorption - drug effects; Tretinoin - administration & dosage; Tretinoin - pharmacokinetics; Antineoplastic agent; Human; Toxicity; Permeation; Retinoids; In vitro; Colloidal gel; Absorption; Skin; Absorption enhancer; Prepolymer; Polyol; Mechanism of action; Topical administration; Tretinoin
• DOI: 10.1021/js9604568
• ISSN: 0022-3549

□ A novel topical tretinoin gel formulation containing a patented TopiCare Delivery Compound, polyolprepolymer-2 (PP-2), was shown to significantly reduce local irritation relative to a marketed tretinoin gel preparation 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 mechanism of action of PP-2 on drug delivery into and through human cadaver skin. Results of these studies have repeatedly shown that a new topical gel formulation containing PP-2 significantly reduces tretinoin penetration while potentially enhancing epidermal deposition compared with a commercial topical gel preparation at the same tretinoin concentration. These studies further support a mechanism of action whereby PP-2 serves as a retentate for drug delivery by formation of a liquid reservoir of polymer and solubilized drug on the skin surface and in the upper layers of the skin, thereby modifying delivery of tretinoin into and through skin. This reservoir of drug and polymer was established within 15min after topical application, and tretinoin was shown to be highly associated with PP-2. These in vitro findings provide a model by which a new tretinoin gel formulation containing PP-2 reduces irritation relative to a commercial tretinoin gel while maintaining clinical efficacy in the treatment of acne vulgaris.