Analysis of macromolecular changes and drug release from hydrophilic matrix systems

The influence of water-soluble and insoluble excipients on dynamics of hydration, front movement, erosion, and drug release from hydrophilic matrix tablets containing water-soluble drug was studied. Tablets were manufactured by direct compression, and their un-constrained swelling behavior and gel strength were assessed with a texture analyzer. Dissolution was performed using USP 26 apparatus II modified by insertion of a mesh to prevent sticking of tablets to the bottom of the vessel and to allow free three-dimensional matrix swelling. Significant release differences between tablet batches were observed and this was consistent with changes in swelling rate, gel thickness, and swelling front movement within the tablets. Matrices containing approximately 30% drug load and water-soluble lactose, demonstrated more pronounced swelling front movement and hence drug release relative to the matrix tablets containing dicalcium phosphate dihydrate. The observed differences in release were verified by calculating the similarity and difference factors. The interdependence of front movement and mass erosion in relation to excipient types on progression of swelling front movement and alteration of water penetration, erosion, and drug release are explained. It is concluded that unlike in conventional dosage forms inclusion of excipients in hydrophilic controlled-release tablets containing water-soluble drugs should be carefully analyzed as their various physico-chemical properties may have significant implications on swelling dynamics, front movement, drug release kinetics, and consequently in vivo performance. (c) 2004 Elsevier B.V. All rights reserved.