(717e) Hydrodynamic Effects of an Arch-Shaped Fiber Optic Probe in a USP Dissolution Testing Apparatus 2

Dissolution testing is widely used in the pharmaceutical industry to evaluate newly developed drug formulations and as a quality control method to insure that solid dosage forms have consistent dissolution property.  Typically, samples are manually drawn from the dissolution vessel prior to analysis.  An approach to overcome the limitations of manual sampling consists in the use of sampling probes, such as fiber optic probes, permanently inserted in the dissolution medium and continually sampling the drug concentration in it 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 study, the hydrodynamic effects introduced by an arch-shaped fiber optic probe in a USP Dissolution Testing Apparatus 2 are studied by: (1) conducting dissolution tests, with and without the probe, using Prednisone tablets fixed at nine different locations at the bottom of the vessel and comparing the dissolution profiles obtained using statistical tools; and (2) 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.  The results show that the arch shaped fiber optic probe does have a baffling effect on the hydrodynamics in the dissolution vessel.  This effect results in changes in the velocities in the fluid flow, and therefore in changes in the dissolution rate of the tablets undergoing testing.  The baffle effect is observed mainly in the region where the probe is inserted.  However, this perturbation is also found to reach the region below the impeller and to change the velocity profile there, resulting in differences in dissolution profiles when the tablets are fixed at positions that are downstream of the probe and within the low velocity region below the impeller. On the other hand, the hydrodynamic effect generated by the probe does not appear to be particularly strong. In most dissolution testing runs, the changes in dissolution profile are not large enough to fail the tests, according to the FDA criteria (f₁ and f₂ values).  The PIV measurements additionally show that the baffle effect is not strong enough to break the overall flow pattern, or to affect the region around the impeller, which is dominated by the main flow generated by the impeller. It can be concluded that the hydrodynamic effects generated by the arch-shaped fiber optic probe are real and observable, resulting in slightly modification of the fluid flow in the dissolution vessel and therefore in detectable differences in the dissolution profiles.  However, these effects are limited and do not typically lead to dissolution testing failures.