ABSTRACT
Changes to hydrodynamics arising from changes within dissolution testing systems, such as the fill volume level, can potentially cause variability in dissolution results. However, the literature on hydrodynamics in Apparatus 1 is quite limited and little information is available for vessels with different liquid volumes. Here, velocities in a USP Apparatus 1 vessel with a liquid fill volume of 500 mL, a common alternative to 900 mL, were experimentally measured using 2D-2C Particle Image Velocimetry (PIV) for different basket rotational speeds. Tangential velocities dominated the flow field, while axial and radial velocities were much lower and varied with location. The velocities distribution increased proportionately with the basket rotational speed almost everywhere in the vessel excepting for underneath the basket. A nearly horizontal radial liquid jet was found to originate close to the basket upper edge. Comparison of these results with those previously reported with 900-mL liquid volume (Sirasitthichoke et al., Intern. J. Pharmaceutics:X; 3 (2021) 100078) showed that the flow rate through the baskets was similar in both systems, implying that, at least initially, the amount of drug in solution would increase linearly with time. In other words, the flow rate through the baskets would be independent of the liquid volume. Velocity profiles were also found to be similar, except in the region above the basket, which was affected by the radial jet with an orientation significantly different between the 500-mL and the 900-mL systems.
Subject(s)
Biopharmaceutics , Hydrodynamics , Computer Simulation , Solubility , Rheology/methodsABSTRACT
PURPOSE: A Design of Experiments (DOE) analysis driven by Computational Fluid Dynamics (CFD) simulations was used to evaluate individual and two-factor interaction effects of varying select geometric and operational parameters on the hydrodynamics in dissolution apparatus 2 (paddle apparatus). METHODS: Simulations were run with meshing controls and solution strategies retained from a mesh-independent validated baseline model. Distance between vessel and impeller bottom surfaces, impeller offset, vessel radius and impeller rotation speed were considered as input parameters. The velocity magnitudes at four locations near the vessel bottom surface were considered as output parameters. Response surfaces and Pareto charts were generated to understand individual and two-factor interaction effects of input parameters on the output parameters. RESULTS: Impeller offset has a dominating influence of a linear and quadratic nature on the output parameters and affects overall hydrodynamics. Changes to other input parameters have limited influence on velocity magnitudes at locations closest to the vessel axis and on overall hydrodynamics. However, these parameters have important influences of varying degrees on velocity magnitudes at locations away from the vessel axis. CONCLUSIONS: The hydrodynamics in Apparatus 2 is influenced differently by different parameters and their combinations. Impeller offset has a stronger influence when compared to parameters that do not alter apparatus symmetry.
Subject(s)
Hydrodynamics , Computer Simulation , SolubilityABSTRACT
The USP Apparatus 1 (basket apparatus) is commonly used to evaluate the dissolution performance of oral solid dosage forms. The hydrodynamics generated by the basket contributes, in general, to the dissolution rate and hence the dissolution results. Here, the hydrodynamics of Apparatus 1 was quantified in a vessel filled with 900-mL de-ionized water at room temperature by determining, via Particle Image Velocimetry (PIV), the velocity profiles on a vertical central plane and on 11 horizontal planes at different elevations at three different basket agitation speeds. The flow field was dominated by the tangential velocity component and was approximately symmetrical in all cases. Despite all precautions taken, small flow asymmetries were observed in the axial and radial directions. This appears to be an unavoidable characteristic of the flow in Apparatus 1. The magnitudes of the axial and radial velocity components varied with location but were always low. A small jet was seen emanating radially near the top edge of the basket. Velocities typically scaled well with increasing agitation speed in most regions of the vessel except for a region directly below the basket. The results of this work provide a major insight into the flow field inside the USP Apparatus 1.
ABSTRACT
PURPOSE: The hydrodynamics in USP dissolution apparatus 3, at five different dip rates, was characterized by analyzing phase-averaged velocity fields obtained using Particle Image Velocimetry (PIV). METHODS: Phase locked 2 Component-PIV (2C-PIV) measurements were recorded on a typical dissolution apparatus 3 configuration with a black painted tablet fixed at the center of the bottom porous screen of the reciprocating cylinder. A trigger mechanism was employed to capture data over 12 phase positions for each reciprocation cycle. Data were captured over a fixed number of cycles, based on dip rate, and the resultant images were post-processed to obtain phase-averaged velocity fields at each phase. RESULTS: For all dip rates studied, the sinusoidal nature of the cylinder's reciprocating motion was evident in the images. The phase positions, in which the cylinder was completely submerged, were characterized by recirculation of liquid through the cylinder, top fitting cap, vessel-cylinder annulus, and bottom fitting cap. The direction of recirculation was opposite for phase positions during the up- and downstrokes. The end positions of the up- and downstrokes were characterized by vortices below and above the cylinder respectively. Increasing dip rates led mainly to increasing velocity magnitudes while all flow characteristics, in general, were retained. CONCLUSIONS: The hydrodynamics in typical USP dissolution apparatus 3 is characterized by cyclic phase-dependent flow fields. Specifically, the velocity field distribution within dissolution apparatus 3 is greatly influenced by the relative position of the top cap to the liquid level in the cylinder.
Subject(s)
Chemistry, Pharmaceutical/instrumentation , Hydrodynamics , Optical Imaging , Particle Size , Rheology , Solubility , Tablets/chemistryABSTRACT
PURPOSE: This study investigated the influence of dip rate on USP Apparatus 3 hydrodynamics in the presence of a solid dosage form (e.g. tablet) using Computational Fluid Dynamics (CFD) simulations. The primary variables of interest were the liquid phase velocity in the computational domain and wall shear stresses on the tablet surfaces. METHODS: Geometry building and model setup were based on a number of simplifying assumptions. Computational grid-independent solutions were achieved for dip rates ranging from 5 to 10 dips per minute (dpm). RESULTS: For all cases studied, the hydrodynamics exhibited a periodicity dictated by the dip rate. Cycle-to-cycle variations were found to be negligible. Higher velocities were predicted in the wake of the tablet and they peaked at midway positions both during the up- and downstrokes of the cylinder. Three sub-regions of velocity were identified inside the reciprocating cylinder. Results also showed localized vortices/recirculations specific to the up- and downstroke, in addition to local stagnation zones. The wall shear stresses and velocity magnitudes scaled proportionately with increasing dip rates while exhibiting qualitatively similar behavior in their spatial and temporal distributions. CONCLUSIONS: Based on the predictions of the 2D axisymmetric CFD model, the hydrodynamics in USP Apparatus 3 is characterized by complex and periodic flow structures.
