Pressure-dependent In-Situ Monitoring of Granular Materials

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The majority of medicines are marketed as oral solid dosage forms and tablets in particular. The building blocks of each tablet include the active ingredient (or drug) and other components (excipients) that when formulated together confer stability, ease of handling and administration, patient compliance and assure delivery of the correct dose of medicine to patients in every tablet. These ingredients are typically presented in granular or powdered form, whether as individual particles, aggregates or formulated intermediates. This proposal seeks to couple an experimental process simulator with advanced measurement to improve our understanding of the relationship between the structure and properties of granular raw materials, compaction processes and the structure and final product performance. This will lead to a range of advances including: predictive or digital formulation design; rapid process development; and digital manufacturing. Consequently, these advances will accelerate the speed with which new medicines can reach the market and reduce costs, which is necessary if we are to realise the supply chains to meet patients' future medicines needs.New pharmaceutical products are far more complex than the standard immediate-release tablets that can be found in simple over-the-counter medicines. The development and manufacture of present-day drugs is much more demanding given the need to achieve target physicochemical and biopharmaceutical properties of the tablet which are themselves a function of more complex molecular and physical properties of the input materials. The advances in the chemistry of such new molecules are staggering, whilst the science that underpins the manufacturing methods used to formulate and produce them is still not very well understood for any given formulation. This necessitates new approaches and technologies to access chemical and physical performance-related material properties during manufacturing development.We will push the limits of existing techniques by integrating state-of-the-art terahertz time-domain spectroscopy into a high-end compaction simulator. This fully integrated system will be capable of monitoring the physical and chemical changes of granular materials during compaction into tablets in situ using terahertz technology. The system will provide an innovative and powerful research platform to address key research challenges in pharmaceutical sciences and manufacturing: analysis of phase transformations in pharmaceutical materials during compression (Theme 1), in-situ monitoring of bulk properties in formulated systems under pressure (Theme 2), digital design of oral pharmaceutical drug products (Theme 3). The outcomes of these research themes are ranging from predicting drug stability (Theme 1) and enabling direct compression by rapid formulation design (Theme 2) to predicting drug performance based on digital process and product design (Theme 3). The equipment will be housed within a well managed, state-of-the-art laboratory facility supported by a dedicated team of academic and support staff. This equipment will provide exciting opportunities for Strathclyde and other UK academics to collaborate and partner with other world-leading groups having complementary analytical facilities and manufacturing processes, thereby creating an international collaborative network of non-duplicated facilities for transnational access. Moreover, the equipment will generate new research opportunities in high value manufacturing, cutting-edge measurement technologies and advanced materials science in partnership with the National Physical Laboratory (NPL), Medicines Manufacturing Innovation Centre (MMIC), Centre for Process Analytics and Control Technology (CPACT), UK industry and academia.