Intelligent Manufacturing of Pharmaceutical Film Coating Using Terahertz Pulsed Imaging, Optical Coherence Tomography and Numerical Modelling

功能性包衣是高度工程化的药物递送系统，其结构和组成对于活性药物成分在人体中的受控释放至关重要。制造复杂性的增加恰逢公司寻求降低成本的时候，而监管机构对该行业施加压力，以确保更好地了解产品的关键质量属性（CQA）和相关的过程控制。迄今为止，这些高价值产品的开发和制造具有挑战性，因为药物加工是复杂的，并且由经验知识主导，在对基本过程的全面科学理解方面存在很大差距。这是一个基本的需求，也是一个巨大的商业机会，开发一个阶跃变化技术-一个“智能工厂”，能够制造这些高价值的产品，以用户定义的规格。EPSRC的这一呼吁为该联盟提供了必要的资金，通过集成过程建模和过程中诊断能力来开发“智能工厂”的基本组件，以实现先进平板电脑制造的实时原位过程控制。通过利用包括太赫兹成像和光学相干断层扫描（OCT）传感器在内的一系列在线传感器获得的独特诊断信息，我们将开发理论模型来识别关键工艺参数，最终允许开发用于先进工艺控制和优化的主动反馈回路。该EPSRC项目将使剑桥和利物浦大学能够在世界领先的制造设备供应商的指导下，利用他们的专业知识和成熟的技术（英国利物浦博世）和一家全球制药公司（辉瑞，三明治，英国）和学术界的支持（比利时根特大学De Beer教授），一家技术型中小企业（TeraView，剑桥，英国），并与监管机构（吴博士，FDA）的额外见解，以提供一个高度先进的制造能力，目前还没有提供给行业。

Functional coatings are highly engineered drug delivery systems whose structure and composition is critical to the controlled release of the active pharmaceutical ingredient in the human body. This increase in manufacturing complexity coincides with a time when companies are looking to reduce costs while regulators exert pressure on the sector to ascertain a greater understanding of the products' critical quality attributes (CQAs) and associated process control. To date the development and manufacture of these high value products is challenging owning to the fact that pharmaceutical processing is complex and dominated by empirical knowledge with large gaps remaining in the full scientific understanding of the underlying processes. It is an essential need, and also a big business opportunity, to develop a step change technology-a "smart factory" capable of manufacturing these high-value products to user-defined specifications. This EPSRC call provides the consortium with the necessary funding to develop the basic components of a "smart factory" by the integration of process modeling and in-process diagnostic capability for real-time in-situ process control of advanced tablet manufacturing. By utilizing the unique diagnostic information obtained by a range of in-line sensors including our THz imaging and optical coherence tomography (OCT) sensors, we will develop theoretical models to identify key process parameters that will ultimately allow the development of an active feedback loop for advanced process control and optimisation. This EPSRC project will allow Cambridge and Liverpool University to use their combined expertise and proven technology, steered by a world leading supplier of manufacture equipment (Bosch, Liverpool, UK) and a global pharmaceutical company (Pfizer, Sandwich, UK) and supported by academia (Professor De Beer, Ghent University, Belgium), a technology SME (TeraView, Cambridge, UK) and with additional insight from the regulators (Dr Wu, FDA), to provide a highly advanced manufacturing capability currently not available to the industry.