Date of Award

Spring 2013

Document Type

Thesis

Degree Name

Master of Science in Pharmaceutical Engineering - (M.S.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Piero M. Armenante

Second Advisor

Laurent Simon

Third Advisor

Gerard Bredael

Abstract

Dissolution testing is routinely used in the pharmaceutical industry to provide in vitro drug release information for drug development and quality control purposes. The USP Testing Apparatus 2 is the most common dissolution testing system for solid dosage forms. Usually, sampling cannulas are used to take samples manually from the dissolution medium. However, the inserted cannula can alter the normal fluid flow within the vessel and produce different dissolution testing results.

The hydrodynamic effects introduced by a permanently inserted cannula in a USP Dissolution Testing Apparatus 2 were evaluated by two approaches. Firstly, the dissolution tests were conducted with two dissolution systems, the testing system (with cannula) and the standard system (without cannula), for nine different tablet positions using non-disintegrating salicylic acid calibrator tablets. The dissolution profiles at each tablet location in the two systems were compared using statistical tools. Secondly, Particle Image Velocimetry (PIV) was used to obtain experimentally velocity vector maps and velocity profiles in the vessel for the two systems and to quantify changes in the velocities on selected horizontal so-surfaces.

The results show that the system with the cannula produced higher dissolution profiles than that without the cannula and that the magnitude of the difference between dissolution profiles in the two systems depended on tablet location. However, in most dissolution tests, the changes in dissolution profile due to the cannula were small enough to satisfy the FDA criteria for similarity between dissolution profiles (f1 and f2 values).

PIV measurements showed slightly changes in the velocities of the fluid flow in the vessel where the cannula was inserted. The most significant velocity changes were observed closest to the cannula. However, generally the hydrodynamic effect generated by the cannula did not appear to be particularly strong, which was consistent to dissolution test results.

It can be concluded that the hydrodynamic effects generated by the inserted cannula are real and observable. Such effects result in slightly mod fications of the fluid flow in the dissolution vessel and in detectable differences in the dissolution profiles, which, although limited, can introduce variations in test results possibly leading to failure of routine dissolution tests.

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