377737 CFD-Predicted and PIV-Measured Velocity Profiles in a USP Dissolution Testing Apparatus 2 Equipped with an Arch-Shaped Fiber Optic Probe and Their Impact on Tablet Dissolution

Monday, November 17, 2014: 2:35 PM
203 (Hilton Atlanta)
Bing Wang, Chemical Engineering, New Jersey Institute of Technology, Newark, NJ, Gerard Bredael, Merck & Co., Inc. , Summit and Piero M. Armenante, Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ

Dissolution testing is a critical tool in drug formulation and product quality assessment.  This test is a routinely used in pharmaceutical development to evaluate the in vitro performance of solid dosage forms, determine the dissolution behavior of formulations and provide an optimization of drug release dosage forms, and as a quality control tool to insure that solid dosage forms have consistent dissolution properties.  The USP Dissolution Testing Apparatus 2 is the device most commonly used for this purpose.  In a typical test, a tablet is added to the vessel and samples are manually withdrawn from the vessels over time and analyzed for their drug content.  An approach to overcome the limitations of manual sampling requires using sampling probes, such as fiber optic probes, permanently inserted in the dissolution medium and continually monitoring drug concentration as the solid dosage form dissolves.  Despite their advantages, permanently inserted fiber optic probes can alter the normal fluid flow within the vessel and produce different dissolution testing results.

In this work, the hydrodynamic changes introduced by an arch-shaped fiber optic probe in a USP Dissolution Testing Apparatus 2 filled with 900 mL of dissolution medium were studied by (1) experimentally determining the velocity profiles in the vessel, with and without the probe, using Particle Image Velocimetry (PIV) and quantifying changes in the flow velocities on selected horizontal iso-surfaces; and (2) predicting the velocity distribution using Computational Fluid Dynamics (CFD).  These results so obtained were used to analyze the dissolution data from of actual dissolution tests conducted with and without the probe using Prednisone tablets fixed at nine different locations at the bottom of the vessel.

In general, substantial agreement was found between the PIV data and the CFD predictions.  The velocities in the upper region of the vessel where the probe is located were clearly affected by the presence of the probe.  More importantly, the some velocity components near the vessel bottom where the tablet is usually located, were found to be appreciably affected by the presence of the probe.  Specifically, both the simulation results and PIV data show that the axial velocities near the bottom are larger in the probe system than in the standard system. In addition, in the region just under the probe, the differences in axial velocities between the two systems are the largest in both of the simulation and PIV measurement, but they become progressively smaller at locations further away from the probe. 

The results of this work indicate that that the arch shaped fiber optic probe introduces as small but measurable baffling effect on the hydrodynamics in the dissolution vessel.  This effect results in changes in the flow velocities which parallel the results of dissolution tests, where the dissolution profiles were typically found to be higher in the presence of the probe, but not sufficiently high to fail the tests, according to the FDA criteria (f1 and f2 values). 

In summary, the hydrodynamic effects generated by the arch-shaped fiber optic probe are small but clearly measurable.  The changes in velocity profiles in the dissolution vessel result in in detectable differences in the dissolution profiles, although not high enough to cause test failures per se.  However, these differences could contribute to amplify the difference in dissolution profiles in those cases in which tablet has an intrinsically higher release rate.

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