Hydrodynamic, Mass Transfer, and Dissolution Effects Induced by Tablet Location during Dissolution Testing

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. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1511-1531, 2009