Transferring pharmaceutical batch technology to continuous flow

Abstract

The current trend in the pharmaceutical industry is towards continuous flow processes. Continuous flow reactor technology can produce a cheaper, better quality product at reduced energy and environmental cost through more efficient mass and heat transfer. It also enables a simplified and faster approach to bulk production by scaling out as opposed to scaling up. The research presented here focuses on the configuration and installation of a continuous flow system into the laboratory, and the transfer of a Meerwein-Ponndorf-Verley (MPV) reduction from batch to continuous mode. The Corning® glass continuous flow reactor in our laboratory utilizes specially-designed mixing structures for enhanced mass transfer. Additionally, the glass reactor offers nonreactivity and corrosion resistance over a wide range of temperature and pressure, which conventional steel reactors do not allow. The MPV reduction is a well-known method to prepare primary and secondary alcohols from aldehydes and ketones, respectively. The traditional MPV reduction protocol (Al(OiPr)₃ in isopropanol) was modified to enable the technological transfer from batch to continuous mode. This is the first time MPV reduction reactions were carried out in continuous mode. As a result, the MPV reduction of the model compound, benzaldehyde, was successfully conducted with 60% less catalyst and product yield was improved up to 20% (average of 10%) in continuous flow reactions as compared to current batch technology. These results are being used to develop a technology roadmap for the pharmaceutical industry to implement continuous flow processes in their manufacturing operations.