Toward a More Reliable USP Dissolution Testing Apparatus II

In the pharmaceutical industry, dissolution testing is a critical step in quality control and a standard method for assessing batch-to-batch consistency of solid oral drug delivery systems, such as tablets. One of the most widely used dissolution test devices is the UPS Apparatus II (paddle). Even to this day, dissolution testing remains susceptible to significant error and test failures. Previous studies indicate that poor reproducibility of dissolution testing data and inconsistency of dissolution results can arise from the complex hydrodynamics present in the unbaffled, hemispherical-bottom, agitated vessel that constitute the UPS Apparatus II. In previous work, our group investigated the hydrodynamics in the standard UPS apparatus II and showed that the velocity distribution in the bottom region of the vessel, where the tablet is typically located and where dissolution occurs, is highly non-uniform and the flow pattern is highly variable. In this work, a modified USP Apparatus II was constructed in which the impeller was placed 8 mm off center. Dissolution tests where calibrators tablets (Prednisone) were placed at different positions on the vessel bottom were conducted using both the standard USP Apparatus II and the modified apparatus. The dissolution profiles were compared with each other and the difference factors f1 and the similarity factors f2 were calculated from the dissolution profiles. The dissolution profiles in the modified apparatus were not significantly affected by tablet location as confirmed by the value of the factors f1 and f2 ,which were well within the accepted ranges and did not change appreciably with the tablet location. By contrast, the corresponding dissolution tests in the standard apparatus failed these similarity tests. In addition, the flow fields near the vessel bottom were obtained via CFD simulation and were found to be significantly more uniform in the modified USP Apparatus II than in the standard apparatus. The proposed modified apparatus has the potential of becoming a valid alternative to the standard USP dissolution testing apparatuses used for dissolution testing.