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

In the pharmaceutical industry, dissolution testing is routinely carried out to determine the dissolution rate of oral solid dosage forms. Among several testing devices, the USP Dissolution Apparatus 2 is the device most commonly used. However, despite its widespread use, this apparatus has been shown to produce test failures and to be very sensitive to a number of small geometry changes.

The objective of this study was to determine whether a novel dissolution system termed “OPI” for “off-center paddle impeller” was sensitive enough to determine differences in tablet dissolution profiles caused by different compression pressure during the tablet manufacturing process. The OPI Dissolution System simply consists of a modified Apparatus 2 in which the impeller is placed 8mm off center in the vessel.

In this work, aspirin tablets were manufactured from powder with a manual tablet press using three different compression pressures. The dissolution profiles of these tablets were then obtained in both the OPI system and the standard USP Apparatus 2 system. Tests were conducted by dropping the tablets in the vessels at the beginning of an experiment, and, in separate experiments, by initially immobilizing the tablets on the vessel bottom at nine different locations. This approach has been used in the past by our group to determine the sensitivity of the dissolution apparatus to minor changes in the geometry of the dissolution system.

All dissolution profiles were found to be affected by the compression pressure. Faster dissolution profiles were obtained at lower compression pressures. When tablets were dropped in the vessel, a comparison of the dissolution profiles obtained in the standard Apparatus 2 system and in the OPI system showed that similarly manufactured tablets produced statistically similar dissolution profiles in both systems, i.e., that the OPI system was just as sensitive as the standard system to variations in the tablet manufacturing process. However, when the tablets were immobilized during the dissolution process, the standard system generated very different dissolution profiles even for tablets manufactured at the same compression pressure. By contrast, the dissolution profiles in the OPI system for tablets manufactured at different pressure but located at different positions were very similar.

It can be concluded that the OPI system is sensitive enough to detect differences in intrinsic tablet dissolution rates (such as those caused, as in this case, by changes in the manufacturing process), while being unaffected by small changes in the system geometry that instead caused the standard system to fail. Therefore, the OPI system appears to be a more reliable dissolution testing apparatus than the current apparatus.

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