470108 Hydrodynamics and Mass Transfer Effects in Mini Vessel Dissolution Testing Systems

Thursday, November 17, 2016: 4:43 PM
Continental 4 (Hilton San Francisco Union Square)
Bing Wang1, Piero M. Armenante1 and Gerard Bredael2, (1)Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, (2)Merck & Co., Inc. , Summit

In the pharmaceutical industry, dissolution testing is routinely conducted to evaluate the in vitroperformance of solid dosage forms in pharmaceutical development, 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 In a typical test, a tablet is added to the vessel and samples are manually withdrawn from the vessels over time and analyzed for their drug content.

The USP 2 drug dissolution testing method is not always appropriate, especially for dissolution testing involving very small tablets or when not enough drug substance may be available for proper dissolution testing in the USP 2 Apparatus, especially during the initial stage of drug development. Small-volume dissolution testing apparatuses (mini vessel systems) can be advantageously used instead of the standard USP 2 system to overcome these limitations. The most common of these mini vessel systems is similar in shape and operation to the USP 2 apparatus, but it only requires a small volume vessel (200 mL) and a mini paddle impeller.

Before mini vessel systems can gain wide acceptance in industry, their hydrodynamics needs to be studied, and their operating conditions must be defined in order to compare the velocity distribution and mass transfer coefficient in a mini vessel system with those in the standard USP2 system. Very few studies on mini vessel systems are available. Therefore, the objective of this work was to quantify the hydrodynamics and drug mass transfer rates in mini vessel systems, and determine the operating conditions under which mini vessel systems can be reliably used instead of USP 2 system for dissolution testing purposes.

The velocity distribution in a minivessel was obtained here using Computational Fluid Dynamics (CFD) at different agitation speeds. The predictions were compared to the velocity vector maps obtained using Particle Image Velocimetry (PIV). Four horizontal iso-surfaces were selected to be studied in detail. The CFC predicted and PIV measured flow patterns were found to be in good agreement. As expected, the 3D flow velocity magnitude increased as the agitation speed increased. However, the velocity in the inner core region below the impeller always remained very low.

The tablet-medium mass transfer process was additionally modeled, and the mass transfer coefficients at four different agitation speeds were obtained and compared to the standard system. The mini vessel system has a flow pattern similar to that of the standard USP 2 system. It was found that similar velocities at the tablet surface (on the iso-surface at y=7mm, i.e., at the vessel bottom) in the mini vessel system and in the USP 2 system were obtained when the mini vessel was operated a 100 mL, 125 rpm and the USP 2 system was operated at 900rpm and 100rpm, indicating that these two systems should result in similar dissolution profiles when operated under these conditions.

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