Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients

Abstract

Continuous flow chemistry has opened a new paradigm in both the laboratory and pharmaceutical industry. This review details the recently reported literature on continuous multistep telescoped synthesis of active pharmaceutical...

Will the next generation of chemical plants be in miniaturized flow reactors?

“…78,79 Combined to intelligent algorithms, it would ultimately lead to autonomous flow platforms able to self-plan and -execute its own synthetic pathway to designated target molecules. [79][80][81] Whereas this road might take some times, efficient black-box algorithms have proven their effectiveness. These algorithms do not require information on the reaction studied and focus on identifying an optimum (yield) rather than generating data to develop reaction models.…”

Analytical Tools Integrated in Continuous-Flow Reactors: Which One for What?

“…Fine chemical industries and organic synthesis research laboratories are facing a digital revolution that is going to profoundly modify the way chemists think and perform chemical transformations. − Chemistry 4.0, which has been coined to define the chemistry of the fourth industrial revolution, massively takes advantage of integrated information technology systems, algorithms, and automated machines to reinvent the concepts of synthesis and production established after the Second World War. − Both research laboratories and multipurpose plants 4.0 will be miniaturized, highly modular, (semi)­autonomous, and connected, increasing safety and sustainability (smaller size) and reducing cost (modularity and autonomy). − To reach the objectives of Chemistry 4.0, chemical synthesis will mainly operate in continuous-flow mode as this technology offers enhanced safety, better reaction control, on-the-fly monitoring, and easier automation compared to traditional batch reactors. ,− Moreover, from a more fundamental point of view, flow chemistry offers the possibility to access “forbidden” transformations as it allows one to explore new process windows and also strongly accelerates kinetics through improved heat and mass transfer. , Critical to the control of continuous processes is the efficient monitoring of process parameters and product quality by process analytical technology (PAT) . At the initiative of the United States Food and Drug Administration (USFDA), PAT was initially introduced in the pharmaceutical industry to enhance and control manufacturing processes with the aim of achieving quality by design (QbD).…”

Scaled up and telescoped synthesis of propofol under continuous-flow conditions

“…The use of continuous flow technologies for this purpose [ 2 – 6 ] is now prominent in both academia and industry, showing great advantages over the traditional batch processes. This is especially true in terms of sustainability, efficiency, safety, and fine reaction control, thus being a disruptive and modern frontier technology [ 7 – 9 ].…”