Simulating the hydrodynamic conditions in the united states pharmacopeia paddle dissolution apparatus

Abstract

KEYWORDS: computational fluid dynamics (CFD), USP paddle apparatus, dissolution, hydrodynamics, modeling The objective of this work was to examine the feasibility of developing a high-performance computing software system to simulate the United States Pharmacopeia (USP) dissolution apparatus 2 (paddle apparatus) and thus aid in characterizing the fluid hydrodynamics in the method. The USP apparatus was modeled using the hydrodynamic package Fluent. The Gambit program was used to create a "wireframe" of the apparatus and generate the 3-dimensional grids for the computational fluid dynamics solver. The Fluent solver was run on an IBM RS/6000 SP distributed memory parallel processor system, using 8 processors.Configurations with and without a tablet present were developed and examined. Simulations for a liquidfilled vessel at a paddle speed of 50 rpm were generated. Large variations in fluid velocity magnitudes with position in the vessel were evident. Fluid velocity predictions were in good agreement with those previously published, using laser Doppler velocity measurements. A low-velocity domain was evident directly below the center of the rotating paddle. The model was extended to simulate the impact of the presence of a cylindrical tablet in the base of the dissolution vessel. The presence of the tablet complicated the local fluid flow, and large fluid shear rates were evident at the base of the compact. Fluid shear rates varied depending on the tablet surface and the location on the surface and were consistent with the reported asymmetrical dissolution of model tablets. The approach has the potential to explain the variable dissolution results reported and to aid in the design/prediction of optimal dissolution conditions for in vitro-in vivo correlations.

Impact of superdisintegrants on efavirenz release from tablet formulations

“…Drug release of a poorly soluble drug like EFV, as used in the study, is usually driven more by the medium than by the formulation ingredients. Discriminatory dissolution profiles are highly desirable for distinguishing between products showing differences in pharmaceutical attributes (formulation or manufacturing process differences) as is the case in the present study, wherein the difference in formulation was only with respect to the disintegrant used (10)(11)(12)(13). Figure 1 shows the dissolution profile of 600-mg EFV tablet in water containing different concentrations of SLS containing CP as disintegrant.…”

Evaluation of Glass Dissolution Vessel Dimensions and Irregularities

“…Differences in the dimensions result in measurable differences in both the paddle tip-vessel wall clearance and in the volume of dissolution media surrounding the paddle. It has been shown that heterogeneous shear rates exist in the hemispheric region of the dissolution vessel (10,11). Given the differences in both the paddle-vessel wall clearance and in the volume of dissolution media surrounding the paddle, hydrodynamics in the hemispheric region of the vessel could be influenced by variability of the dimensions of this critical region of the dissolution vessel.…”

Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review

“…Recirculation loops have been identified in both the upper and lower sections of the vessel, with a weak positive axial flow under the impeller in the center of lower part of the vessel. Overall fluid velocity values and shear rates in the vessel base are very low, especially at the center of the vessel base compared to other regions of the vessel (13,21,(24)(25)(26)(27).…”

“…Under the standard operating conditions mandated by the dissolution test procedure, with no tablets present in the vessel, the shear strain environment in USP Apparatus 2 is highly heterogeneous with strain rate and fluid velocities varying significantly along the vessel base (21,(24)(25)(26)(27)29). These heterogeneous hydrodynamic conditions are present in the vessel base region where a dosage form is likely to be located.…”