APPLICATION OF A BINARY POLYMER SYSTEM IN DRUG-RELEASE RATE MODULATION .1. CHARACTERIZATION OF RELEASE MECHANISM

A new binary polymer matrix tablet for oral administration was develop ed. The system will deliver drug at variable rates according to zero-o rder kinetics for total drug content and is manufactured by direct com pression technology. Highly methoxylated pectin and hydroxypropyl meth ylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results i ndicate that by increasing pectin:HPMC ratios, release rates are incre ased, but zero-order kinetics prevail throughout the dissolution perio d (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of visc osities that modulates drug release and results in rapid hydration/gel ation in both axial and radial directions, as evidenced by photomicrog raphic pictures. This hydration-gelation contributes to the developmen t of swelling/erosion boundaries and consequently to constant drug rel ease. Combination of these particular polymers facilitates rapid forma tion of necessary boundaries (i.e., gel layer and solid core boundarie s) to control overall mass transfer processes. The drug fraction relea sed (Mt/M infinity), release kinetics, and mechanism of release were a nalyzed by applying the simple power law expression Mt/M infinity, = k t(n), where k is a kinetic constant and the exponent n is indicative o f the release mechanism. The calculated n values for pectin:HPMC ratio s of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II tr ansport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulate d by the gelling characteristics of polymers in the formulation.