The study of pharmaceutical powder mixing through improved flow property characterisation and tomographic imaging of blend content uniformity

摘要

The regulatory framework in which pharmaceutical companies have to work has changed significantly since the late 1990’s. The development and implementation of risk based approaches to processing pharmaceutical powders allows the pharmaceutical manufacturers the freedom to adopt real-time release for their products whist reducing the regulatory burden for both the statutory bodies and the manufacturers. This thesis has been a collaboration between Buck Systems and the University of Birmingham School of Chemical Engineering to evaluate and develop methods which would enhance the way in which Buck Systems can, in co-operation with their clients, enhance their understanding of how powder properties affect their products that are used in pharmaceutical manufacturing to better comply with the changes in the regulatory environment. To this end simple and quick screening methods for characterisation of customers’ powders with a view to identifying potential problems prior to blending tests have been developed to replace the current ad hoc approach. These include the use of tests that have been relied on historically as well as newer, more universal and robust techniques such as automated shear cells and powder rheometers. Detailed characterisation trials have shown where these techniques can be successfully applied and where their limitations lie. Further work has shown how powder systems can be better evaluated within the existing HAZOP framework. Specific evaluation of the hopper design methodology has resulted in the development of an expert system to enable the rapid sensitivity analysis of design options. In addition the limits of the hopper design method have been explored and some limitations identified where significant overdesign may occur. The evaluation of content uniformity in a laboratory scale blender using specialist Positron Imaging equipment available at the University of Birmingham has also been undertaken. The unique study of the blender contents using Positron Emission Tomography has provided a range of insights into the way binary and ternary powder systems interdisperse.