Design and In Vivo Evaluation of a Patch System Based on Thiolated Polymers

Abstract

A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil‐cysteine conjugate (49%), fluoresceine isothiocyanate‐dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate‐dextran (FD4) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to Male Sprague–Dawley rats. Maximum FD4 concentration in blood of the patch system was 46.1 ± 8.9 ng/mL and was reached 3 h after administration. In contrast cmax of control tablets displayed 50.5 ± 14.9 ng/mL after 2 h and the absorption of FD4 after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD4 is obtained with patches thou with tablets. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:620–627, 2009