Experimental and computational determination of blend time in USP dissolution testing apparatus II

Blend time, the time to achieve a predefined level of homogeneity of a tracer in a mixing vessel, is an important parameter to evaluate the mixing efficiency of mixing devices. In this work, the blend time required to homogenize the liquid content of a USP Dissolution Testing Apparatus II under a number of operating conditions was obtained using two different experimental methods (tracer detection via colorimetric and conductivity measurements), a computational approach (computational fluid dynamics (CFD)), and a semi-theoretical analysis of the phenomenon. Under the standard geometric and operating conditions in which the USP Apparatus II is typically used (N= 50 rpm) the experimental blend time to achieve a 92.74% uniformity level was found to be between 27.5 and 33.3 s, depending on the location of the injection point and monitoring point for the tracer. These values were in close agreement with those obtained from CFD simulations. Changing the impeller vertical position (±2 mm) had only a limited effect. The CFD predictions also indicated that blend time is inversely proportional to the agitation speed. This conclusion is in agreement with previous reports and equations for blend time in mixing vessels. The blend times obtained in this work appear to be some two orders of magnitude smaller than the time usually required for appreciable tablet dissolution during the typical dissolution test, implying that the liquid contents of the USP Apparatus II can be considered to be relatively well mixed during the typical dissolution test.