We characterized the effect of hydroxypropyl methylcellulose (HPMC)/lactose ratio and HPMC viscosity grade (molecular weight) on solute release 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 the swelling process common to all formulations were revealed: (i) swelling is anisotropic with a preferential expansion in the axial direction, (ii) swelling is isotropic with respect to the gel layer thickness and composition in both axial and radial directions, (iii) the gel layer develops in three stages, and (iv) water penetration is Fickian in nature and essentially constant for all formulations. We monitored simultaneously drug, lactose, and HPMC release. Lactose and drug release rates were superimposed, indicating a similar diffusional release mechanism and no interaction with HPMC. The strong dependence of HPMC release on viscosity grade is explained on the basis of the concept of polymer disentanglement concentration. We analyzed drug release rates using a model for a reservoir-type release system that incorporates swelling kinetics. HPMC/lactose ratio modulates drug release rate by altering drug diffusivity, a function of gel composition. In contrast, HPMC viscosity grade impacts matrix dissolution and gel layer thickness development below a critical molecular weight. For slowly dissolving matrices containing high viscosity grade (> 4000 cps) HPMC, similar drug release rates are observed mainly due to the same drug diffusivity as a result of the identical gel composition and thickness. For fast dissolving matrices (< or = 100 cps) swelling inhomogeneity is proposed as being responsible for a higher apparent drug diffusivity and release rate.

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These results are consistent with previous knowledge of the release mechanisms of these formulations. ER adinazolam mesylate and ER alprazolam 0.5 mg exhibit primarily a diffusion controlled release mechanism, while ER alprazolam 3 mg deviates from pure diffusional release. The limitations of the model are discussed and point to the need for continued study of the swelling kinetics of matrix ER systems.