Pressure-dependent In-Situ Monitoring of Granular Materials

颗粒材料的压力相关原位监测

• 批准号: EP/S02168X/1
• 负责人: Alastair Florence
• 金额: $ 66.19万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS02168X%2F1
• 关键词: Pressure; dependent; Situ; Monitoring; Granular

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.

大多数药物尤其是口服固体剂型和片剂。每个片剂的构件包括活性成分（或药物）和其他成分（赋形剂），这些成分（赋形剂）共同配制时，赋予稳定性，易于处理和给药，患者合规性，并确保每个片剂中的患者将正确剂量的药物递送给患者。这些成分通常以颗粒或粉末形式表示，无论是单个颗粒，聚集体还是配方中间体。该建议旨在将实验过程模拟器与高级测量相结合，以提高我们对颗粒原材料，压实过程以及结构以及结构和最终产品性能的结构和性质之间关系的理解。这将导致一系列进步，包括：预测或数字配方设计；快速过程开发；和数字制造。因此，这些进步将加速新药物可以达到市场并降低成本的速度，如果我们要意识到供应链以满足患者的未来药物需求，这是必要的。NEWPharmaceutical产品比可以在简单的非处方药中可以找到的标准立即释放片更为复杂。鉴于需要实现片剂的目标物理化学和生物制药特性，因此当今药物的开发和制造本身就是输入材料的分子和物理性能更复杂的函数。这种新分子化学的进步令人惊讶，而基于用于制定和生产它们的制造方法的科学对于任何给定的配方来说仍然不太了解。这需要新的方法和技术来在制造过程中访问化学和物理性能相关的材料特性。我们将通过将最新的Terahertz Tierahertz Time域光谱范围整合到高端压实模拟器中，以推动现有技术的限制。该完全集成的系统将能够使用Terahertz技术在压实过程中监测颗粒材料的物理和化学变化。该系统将提供一个创新且强大的研究平台，以应对药物科学和制造业中的关键研究挑战：压缩过程中药品材料的相变（主题1），对配方系统下的散装系统的现场监测（主题2），数字化药品的数字设计（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）以及通过快速配方设计（主题2）进行直接压缩到基于数字过程和产品设计的药物性能（主题3）。该设备将安置在一个由良好的学术和支持人员团队支持的管理良好，最先进的实验室设施中。该设备将为Strathclyde和其他英国学者提供激动人心的机会，与其他具有互补分析设施和制造过程的世界领先的团体合作并合作，从而创建了国际非剥夺跨国访问设施的国际协作网络。此外，该设备将与国家物理实验室（NPL），药品制造创新中心（MMIC），工艺分析与控制技术中心（CPACT），英国行业和学术界合作，为高价值制造，尖端测量技术和高级材料科学生成新的研究机会。

项目成果

Effect of Microsphere Concentration and Size in Compacts on Terahertz Scattering

压坯中微球浓度和尺寸对太赫兹散射的影响

• DOI: 10.23919/eumc50147.2022.9784372
• 发表时间: 2022
• 作者: Murphy K

Polymer Pellet Fabrication for Accurate THz-TDS Measurements

用于精确 THz-TDS 测量的聚合物颗粒制造

• DOI: 10.3390/app12073475
• 发表时间: 2022
• 期刊: Applied Sciences
• 作者: Murphy K

Observation of Spurious Spectral Features in Mixed-Powder Compressed Pellets Measured by Terahertz Time-Domain Spectroscopy

太赫兹时域光谱测量混合粉末压缩颗粒中杂散光谱特征的观察

• DOI: 10.1109/tthz.2023.3290118
• 发表时间: 2023
• 期刊: IEEE Transactions on Terahertz Science and Technology
• 影响因子: 3.2
• 作者: Murphy K

Observation of spurious spectral features in mixed-powder compressed pellets measured by terahertz time-domain spectroscopy.

通过太赫兹时域光谱测量混合粉末压缩颗粒中的杂散光谱特征的观察。

• DOI: 10.36227/techrxiv.22692448
• 发表时间: 2023
• 作者: Nfataly M

Analysis of THz Scattering of Compacted Granular Materials using THz-TDS

使用 THz-TDS 分析压实颗粒材料的太赫兹散射

• DOI: 10.1109/irmmw-thz50927.2022.9895792
• 发表时间: 2022
• 作者: Murphy K