Importance of media selection in establishment of in vitro-in vivo relationships for quinidine gluconate

Abstract

The dissolution profiles of two different commercial formulations of controlled release 324 mg quinidine gluconate tablets were investigated and their bioavailability differences were associated with in vitro results. One of the marketed brands which was not approved by the Food and Drug Administration was alleged by some patients to have no therapeutic effect when taken orally. Dissolution profiles using the paddle method at 100 rpm in different dissolution media revealed wide differences between these two products. The dissolution rates of the two products were significantly different in water, acetate buffer pH 5.4 and phosphate buffer pH 5.4. However, the dissolution profiles were similar for the two products with respect to rate and extent in simulated gastric fluid (no enzymes) and pH 7.4 phosphate buffer. Bioavailability data for these two products showed significant differences among various in vivo parameters. A reformulated product with comparable bioavailability to the FDA-approved product also had similar dissolution profiles in the systems studied earlier. These findings confirmed the importance of the screening and judicious selection of dissolution medium as well as the predictive usefulness of a dissolution test in the quality control of sustained (or controlled) released quinidine gluconate formulations.