Abstract
The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process.
Highlights
The last 20 years have witnessed a true renaissance in the way synthetic chemistry is performed due to the implementation of various enabling technologies allowing the modern synthesis chemist to select from a range of tools and equipment to best perform a given transformation [1,2,3,4,5,6]
As this review has clearly demonstrated, flow chemistry has matured from an innovative synthesis concept for improving chemical synthesis to a powerful and widely applicable tool box enabling the efficient multistep synthesis of numerous active pharmaceutical ingredients
Current estimates suggest a general increase in industrial applications of continuous manufacture of pharmaceuticals from 5% to 30% over the few years
Summary
The last 20 years have witnessed a true renaissance in the way synthetic chemistry is performed due to the implementation of various enabling technologies allowing the modern synthesis chemist to select from a range of tools and equipment to best perform a given transformation [1,2,3,4,5,6]. The trend to question the suitability of classical laboratory glassware and to utilise more ‘fit for purpose’ synthesis equipment allows the individual chemists to conduct their research in a more modern fashion, and adjusts their mind-set towards the full practical breadth of synthesis planning. In this way chemists are more aware of the entire processing sequence, considering quenching, work-up, extraction and purification as part of the holistic design of the preparative route.
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