Pressure-dependent In-Situ Monitoring of Granular Materials

大多数药物以口服固体剂型销售，特别是片剂。每个片剂的组成部分包括活性成分（或药物）和其他成分（赋形剂），当它们一起配制时，具有稳定性，易于操作和管理，患者依从性，并确保在每个片剂中向患者提供正确剂量的药物。这些成分通常以颗粒或粉末形式呈现，无论是作为单个颗粒，聚集体还是配制的中间体。本提案旨在将实验过程模拟器与先进的测量方法相结合，以提高我们对颗粒状原材料的结构和性能、压实过程与结构和最终产品性能之间关系的理解。这将带来一系列进步，包括：预测性或数字化配方设计；快速工艺开发；以及数字化制造。因此，这些进步将加快新药进入市场的速度并降低成本，如果我们要实现满足患者未来药物需求的供应链，这是必要的。新型药品比普通非处方药中的标准速释片剂要复杂得多。鉴于需要达到片剂的目标物理化学和生物制药特性，当今药物的开发和制造要求要高得多，而这些特性本身是输入材料更复杂的分子和物理特性的功能。这些新分子在化学上的进步是惊人的，然而，对于任何给定的配方，支撑它们的制造方法的科学仍然没有得到很好的理解。这就需要在制造开发过程中采用新的方法和技术来获取与化学和物理性能相关的材料特性。我们将通过将最先进的太赫兹时域光谱集成到高端压实模拟器中来突破现有技术的极限。这种完全集成的系统将能够使用太赫兹技术监测颗粒材料在原地压实成片剂期间的物理和化学变化。该系统将提供一个创新和强大的研究平台，以解决制药科学和制造中的关键研究挑战：压缩过程中药物材料的相变分析（主题1），压力下配方系统中散装特性的原位监测（主题2），口服药物产品的数字化设计（主题3）。这些研究主题的结果范围从预测药物稳定性（主题1）和通过快速配方设计实现直接压缩（主题2）到基于数字工艺和产品设计预测药物性能（主题3）。这些设备将被安置在一个管理良好的、最先进的实验室设施内，由一个专门的学术和支持人员团队提供支持。该设备将为斯特拉斯克莱德和其他英国学者提供令人兴奋的机会，与其他拥有互补分析设施和制造工艺的世界领先集团合作，从而创建一个跨国访问的非重复设施的国际合作网络。此外，该设备将与国家物理实验室（NPL）、药品制造创新中心（MMIC）、过程分析和控制技术中心（CPACT）、英国工业界和学术界合作，在高价值制造、尖端测量技术和先进材料科学方面产生新的研究机会。

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.