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Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals

机译:紧凑的NMR光谱实现灵活的自动化可连续生产药品

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摘要

Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce reconfiguration for fast product changes. To facilitate this flexibility by real-time quality control, we developed a solution that can be adapted quickly to new processes and is based on a compact nuclear magnetic resonance (NMR) spectrometer. The NMR sensor is a benchtop device enhanced to the requirements of automated chemical production including robust evaluation of sensor data. Beyond monitoring the product quality, online NMR data was used in a new iterative optimization approach to maximize the plant profit and served as a reliable reference for the calibration of a near-infrared (NIR) spectrometer. The overall approach was demonstrated on a commercial-scale pilot plant using a metal-organic reaction with pharmaceutical relevance. Graphical abstract
机译:使用强化连续过程的模块化工厂代表了一种药品生产的吸引人的概念。与批处理相比,它可以提高质量,安全性,可持续性和盈利能力;此外,它还支持即插即用的重新配置,以快速更换产品。为了通过实时质量控制促进这种灵活性,我们基于紧凑型核磁共振(NMR)光谱仪开发了一种可快速适应新工艺的解决方案。 NMR传感器是一种台式设备,可满足自动化化学生产的要求,包括对传感器数据的强大评估。除了监视产品质量外,在线NMR数据还用于一种新的迭代优化方法中,以最大化工厂的利润,并为近红外(NIR)光谱仪的校准提供了可靠的参考。整个方法已在商业规模的中试工厂得到证明,该工厂使用了具有药物相关性的金属有机反应。 <!-fig ft0-> <!-fig @ position =“ position” anchor“ == f4-> <!-fig mode =” anchred“ f5-> <!-fig / graphic | fig / alternatives / graphic mode =“ anchored” m1-> <!-caption a7->图形摘要

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