DRUG-RELEASE FROM HYDROPHILIC MATRICES .2. A MATHEMATICAL-MODEL BASEDON THE POLYMER DISENTANGLEMENT CONCENTRATION AND THE DIFFUSION LAYER

A comprehensive model is developed to describe the swelling/ dissoluti on behaviors and drug release from hydrophilic matrices. The major thr ust of this model is to employ an important physical property of the p olymer, the polymer disentanglement concentration, rho(p,dis), the pol ymer concentration below which polymer chains detach off the gelled ma trix. For (hydroxypropyl) methylcellulose (HPMC) in water, we estimate that rho(p,dis) scales with HPMC molecular weight, M, as rho(p,dis) p roportional to M(-0.8). Further, matrix dissolution is considered simi lar to the dissolution of an object immersed in a fluid. As a result, a diffusion layer separating the matrix from the bulk solution is inco rporated into the transport regime. An anisotropic expansion model is also introduced to account for the anisotropic expansion of the matrix where surface area in the radial direction dominates over the axial s urface area. The model predicts that the overall tablet size and the c haracteristic swelling time correlate with rho(p,dis) qualitatively. T wo scaling laws are established for fractional polymer (m(p)(t)/m(p)(i nfinity)) and drug (m(d)(t)/m(d)(infinity)) released as m(p)(t)/m(p)(i nfinity) proportional to M(-1.05) and m(d)(t)/m(d)(infinity) proportio nal to M(-0.24), consistent with the limiting polymer molecular weight effect on drug release. Model predictions for polymer and drug releas e agree well with observations, within 15% error. Evolution of water c oncentration profiles and the detailed structure of a swollen matrix a re discussed.