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Anal Bioanal Chem ; 411(14): 3037-3046, 2019 May.
Article in English | MEDLINE | ID: mdl-30903225

ABSTRACT

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.


Subject(s)
Magnetic Resonance Spectroscopy/methods , Pharmaceutical Preparations/chemical synthesis , Automation , Calibration , Equipment Design , Multivariate Analysis , Pilot Projects , Quality Control , Spectroscopy, Near-Infrared/methods
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