Hydrodynamic characterization of the USP Apparatus 2 dissolution test

Drug dissolution testing is a valuable tool for characterizing drug product performance. In a research setting, it serves as a guide during formulation development and the prediction of in vivo performance. As a quality control tool, it is used to test internal and batch-to-batch variability of manufacturing lots before release to the market. Despite the reliance of the FDA, the USP, and the pharmaceutical industry on dissolution testing, the test itself is poorly understood and often produces inconsistent or inaccurate measurements.; The USP Apparatus 2 dissolution test, the most commonly used official dissolution device, uses a flow design and a set of conditions that have been shown to generate highly variable results. Numerous studies in the literature have shown that hydrodynamics strongly influence dissolution test measurements. However, the flow properties and mixing characteristics within this device are not well understood.; The goal of this research was to conduct a thorough examination of the hydrodynamic factors affecting tablet dissolution in the USP Apparatus 2 test. Computational and experimental tools are used to study the flow phenomena within the device. An examination of the hydrodynamics shows that the test is highly vulnerable to flow and mixing problems that can affect testing performance and consistency. The studies reveal that the shear field within the device is not uniform, and dissolution test results can vary dramatically with the position of the tablet within the vessel. The presence of dense particle suspensions magnify the problems, yielding more inconsistency and inaccuracy in measurements.