SWELLING OF HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS .2. MECHANISTIC STUDY OF THE INFLUENCE OF FORMULATION VARIABLES ON MATRIX PERFORMANCE AND DRUG-RELEASE

We characterized the effect of hydroxypropyl methylcellulose (HPMC)/la ctose ratio and HPMC viscosity grade (molecular weight) on solute rele ase and swelling of matrix tablets. We used a semiquantitative optical imaging method to monitor the swelling of matrices with HPMC content from 20% to 80% (w/w) and four viscosity grades. Several aspects of th e swelling process common to all formulations were revealed: (i) swell ing is anisotropic with a preferential expansion in the axial directio n, (ii) swelling is isotropic with respect to the gel layer thickness and composition in both axial and radial directions, (iii) the gel lay er develops in three stages, and (iv) water penetration is Fickian in nature and essentially constant for all formulations. We monitored sim ultaneously drug, lactose, and HPMC release. Lactose and drug release rates were superimposed, indicating a similar diffusional release mech anism and no interaction with HPMC. The strong dependence of HPMC rele ase on viscosity grade is explained on the basis of the concept of pol ymer disentanglement concentration. We analyzed drug release rates usi ng a model for a reservoir-type release system that incorporates swell ing kinetics. HPMC/lactose ratio modulates drug release rate by alteri ng drug diffusivity, a function of gel composition. In contrast, HPMC viscosity grade impacts matrix dissolution and gel layer thickness dev elopment below a critical molecular weight. For slowly dissolving matr ices containing high viscosity grade (>4000 cps) HPMC, similar drug re lease rates are observed mainly due to the same drug diffusivity as a result of the identical gel composition and thickness. For fast dissol ving matrices (less than or equal to 100 cps) swelling inhomogeneity i s proposed as being responsible for a higher apparent drug diffusivity and release rate.