Simulations of hydrodynamics in the paddle dissolution apparatus and dissolution from multi-layered compacts

Abstract

Studies involving the calculation of dissolution rates from individual surfaces of large single component compacts, to assist in the prediction of dissolution rates from simple layered compact systems, revealed that non-uniform hydrodynamics were present in the paddle dissolution apparatus. Dissolution fluxes varied depending on the location of the surface from where dissolution occurred and also on the position of the compact in the vessel, with highest dissolution rates occurring for compacts within a region of 3 mm from the base of the vessel. A virtual Computational Fluid Dynamics model of the paddle dissolution apparatus was developed and validated against previously measured fluid velocities in the apparatus. The method revealed that fluid flow behaviour below the level of the paddle was complicated, with large changes in velocity occurring over small distances. High fluid shear rates were noticeable towards the base of a large compact positioned at the bottom of the vessel, consistent with the observed increased dissolution rates in this region. Laminar flow was predicted for paddle rotation speeds of up to 150 rpm. Times to achieve complete mixing in the vessel were dependant on the paddle rotation speed. A mass transfer prediction made for the top surface, based on the angular rotation of the fluid in this region was in close agreement with the corresponding experimentally determined result. A semi analytical solution was developed to describe dissolution from the curved surface of a compact sitting at the base of the vessel based on the examination of fluid shear rates in the axial direction in the diffusion boundary layer immediately outside the curved surface. The predicted mass transfer rate was higher than the experimentally determined dissolution rate, the deviation being explained in terms of the shortcomings of the assumptions of the model. The validated CFD method could be used in future work to examine the effect of various parameters on the hydrodynamics or mixing properties within the apparatus and may ultimately prove a useful tool in the examination of the hydrodynamic relations in in-vitro in-vivo correlations (IVIVC).