A NEW TRANSMUCOSAL THERAPEUTIC SYSTEM FOR THE SYSTEMIC DELIVERY OF ISOSORBIDE DINITRATE - IN-VITRO AND IN-VIVO EVALUATION IN BEAGLE DOGS

A new transmucosal therapeutic system was developed for the controlled systemic delivery of isosorbide dinitrate. Transmucosal therapeutic s ystem is a tract-field shaped device consisting of a fast release laye r and a sustained release layer. A combination of polyvinylpyrrolidone and D-mannitol or polyacrylic acid was used as the matrix. The releas e of isosorbide dinitrate from the transmucosal therapeutic system for mulation was controlled both by diffusion through the swelled gel laye r and by erosion of the gel layer, and followed first-order kinetics. The in vivo release of isosorbide dinitrate from the fast and sustaine d release layers had first-order rate constants of 4.15 and 0.22 h(-1) , respectively, while oral mucosal absorption had a first-order step f or transmucosal systemic delivery was the release of isosorbide dinitr ate from the transmucosal therapeutic system formulation. Thus, the pl asma concentration profile of isosorbide dinitrate can be controlled b y adjusting the rate of isosorbide dinitrate dissolution from the tran smucosal therapeutic system formulation in the oral cavity. The optimi zed transmucosal therapeutic system formulation was administered to be agle dogs. This final transmucosal therapeutic system formulation exhi bited an immediate rise in the plasma level of isosorbide dinitrate an d maintained the minimum effective concentration over a long period as designed.