Micro reactor and flow chemistry for industrial applications in drug discovery and development

Abstract

In this review, case studies focused on syntheses of active pharmaceutical ingredients, intermediates and lead compounds are reported employing micro reactors and continuous fl ow technology in areas such as medicinal chemistry, chemical development and manufacturing. The advantages of fl ow technology are currently very clear as opposed to conventional batch methods. Most strikingly and relevant for pharmaceutical ' s time-to-market needs, fl ow processing has the important advantage of the ease with which reaction conditions can be scaled. As this technology is new and has major full-process scale implications, we also wanted to point out that this cannot be applied and released to all chemistries yet, thereby also critically mirroring disadvantages and advantages of the step-change technology. However, the positive impact has been dominating and thus pharmaceutical and fi ne-chemical industries have increased their awareness and interest in fl ow chemistry applications. Beyond pharmaceutical syntheses, this review aims to conclude with the special needs of pharmacy on fl ow and micro reactor chemistry, which is not the same as for the fi ne-chemical industry. Here, the needs of Brazil are considered, as the mirroring of micro reactor and fl ow chemistry was done from a European -academic and business -perspective. The hope is to stimulate and promote fl ow developments in emerging developing nations.

A Microfluidic Toolbox for the Development of In-Situ Product Removal Strategies in Biocatalysis

“…In some cases, they have also been used for actual manufacturing of fine chemicals and pharmaceuticals [37,39,40]. The aim here is to highlight how that knowledge can be transferred and applied to the development of intensified biocatalytic processes exploiting ISPR concepts and principles.…”

Sustainability lessons from practice: how flow intensification can trigger sustainability and modular plant technology in EU projects

“…[44,45] The production of naproxen in batch mode is welldocumented. [46] The production of naproxen by the Syntex process is elaborated in Fig.…”

Biocatalytic process development using microfluidic miniaturized systems

“…Such technologies are sometimes referred to as micro unit operations (MUOs), where the basic concept is to have conventional large scale equipment mimicked at a micro scale (e.g., reactors and separators [12]). However, microfluidic devices also enable novel process development methods [13][14][15]. At small scale, different physical effects dominate the flow compared to larger scale technologies.…”