Shear distribution and variability in the USP Apparatus 2 under turbulent conditions.

Computational analysis is used to examine the hydrodynamic environment within the USP Apparatus II at common operating conditions. Experimental validation of the computational model shows that the simulations of fluid motion match the dispersion of dye observed in experiments. The computations are then used to obtain data that cannot be easily measured with experiments, specifically the distribution of shear forces within the media and along the wall. Results show that the shear environment is highly non-uniform. Increasing the paddle speed from 50 to 100 rpm does not improve shear homogeneity within the apparatus. Experiments show that this uneven distribution of hydrodynamic forces is a direct cause of dissolution testing variability. This variability is large enough to cause for type II dissolution test failures, i.e., failures are a result of a vulnerability of the testing method rather than a problem with a dosage form. Future development of new dissolution tests should include evaluations of the hydrodynamic environments to eliminate this potential source of failure that is unrelated to product quality.