A simple systematic optimization approach was applied to tailor the drug release profile from a hydrophilic matrix extended-release tablet. When the ratio of anionic and nonionic polymers was optimized, pH-independent in vitro release of the model drug verapamil hydrochloride was obtained. The mechanisms of drug release at the pH extremes were evaluated by graphical analysis of the dissolution data and direct examination of the tablets during dissolution. Graphical evaluation did not completely clarify the release control mechanisms involved. Direct examination of tablets during dissolution, with estimation of amounts of drug and excipients dissolved at different times, gave further insight into relative contribution of mechanisms at different pH values. The change from predominantly diffusional to predominantly erosional mechanisms as pH is increased provides for the pH-independent release observed. This understanding should help model the application of this approach to other drugs.