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Tablets undergoing dissolution in the USP Dissolution Testing Apparatus II are often found at locations on the vessel bottom that are off-center with respect to the dissolution vessel and impeller. A previously validated CFD approach and a novel experimental method were used here to examine the effect of tablet location on strain rates and dissolution rates. Dissolution tests were conducted with non-disintegrating tablets (salicylic acid) and disintegrating tablets (Prednisone) immobilized at different locations along the vessel bottom. CFD was used to predict the velocity profiles and strain rates when the tablets were placed at such locations. A CFD-based model was derived to predict the mass transfer coefficient and dissolution curves, which were then compared to the experimental results. Both non-disintegrating and disintegrating off-center tablets experimentally produced higher dissolution rates than centered tablets. The CFD-predicted strain rate distribution along the bottom was highly not uniform and the predicted strain rates correlated well with the experimental mass transfer coefficients. The proposed CFD-based model predicts mass transfer rates that correlate well with the experimental ones. The exact tablet location has a significant impact on the dissolution profile. The proposed model can satisfactorily predict the mass transfer coefficients and dissolution profiles for non-disintegrating tablets. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1511–1531, 2009 [ABSTRACT FROM AUTHOR]

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. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3072–3086, 2007 [ABSTRACT FROM AUTHOR]

The USP Apparatus II is the device commonly used to conduct dissolution testing in the pharmaceutical industry. Despite its widespread use, dissolution testing remains susceptible to significant error and test failures, and limited information is available on the hydrodynamics of this apparatus. In this work, laser-Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were used, respectively, to experimentally map and computationally predict the velocity distribution inside a standard USP Apparatus II under the typical operating conditions mandated by the dissolution test procedure. The flow in the apparatus is strongly dominated by the tangential component of the velocity. Secondary flows consist of an upper and lower recirculation loop in the vertical plane, above and below the impeller, respectively. A low recirculation zone was observed in the lower part of the hemispherical vessel bottom where the tablet dissolution process takes place. The radial and axial velocities in the region just below the impeller were found to be very small. This is the most critical region of the apparatus since the dissolving tablet will likely be at this location during the dissolution test. The velocities in this region change significantly over short distances along the vessel bottom. This implies that small variations in the location of the tablet on the vessel bottom caused by the randomness of the tablet descent through the liquid are likely to result in significantly different velocities and velocity gradients near the tablet. This is likely to introduce variability in the test. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2327–2349, 2007 [ABSTRACT FROM AUTHOR]