A NEW TERNARY POLYMERIC MATRIX SYSTEM FOR CONTROLLED DRUG-DELIVERY OFHIGHLY SOLUBLE DRUGS .1. DILTIAZEM HYDROCHLORIDE

Purpose. The purpose of this study was to develop a new ternary polyme ric matrix system that is easy to manufacture and that delivers a high ly soluble drug over long periods of time. Methods. Pectin, hydroxypro pylmethylcellulose (HPMC), and diltiazem HCl granulated with gelatin a t optimized ratios were blended at different loading doses and directl y compressed. Swelling behavior, dissolution profiles and the effect o f hydrodynamic stress on release kinetics were evaluated. Results. Dil tiazem release kinetics from the ternary polymeric system was dependen t on the different swelling behavior of the polymers and varied with t he drug loading dose and hydrodynamic conditions. Drug release followe d either non-Fickian or Case II transport kinetics. The relative influ ence of diffusion and relaxational/dissolution effects on release prof iles for different drug loadings was calculated by a nonlinear regress ion approach. Photographs taken during swelling show that the anisotro pic nature of the gel structure, drug loading dose, swelling capacity of polymers used, and the design of delivery system all play important roles in controlling the drug release and dissolution/erosion process es. Conclusions. Zero-order delivery of diltiazem HCl from a simple ta blet matrix was achieved. The ternary polymeric system developed in th is study is suitable for controlled release of highly soluble drugs. I t offers a number of advantages over existing systems, including ease of manufacturing and of release modulation, as well as reproducibility of release profiles under well defined hydrodynamic conditions. Our d elivery system has the potential to fully release its drug content in a controlled manner over a long time period and to dissolve completely .