Reactor Selection for Effective Continuous Biocatalytic Production of Pharmaceuticals

Abstract

Enzyme catalyzed reactions are rapidly becoming an invaluable tool for the synthesis of many active pharmaceutical ingredients. These reactions are commonly performed in batch, but continuous biocatalysis is gaining interest in industry because it would allow seamless integration of chemical and enzymatic reaction steps. However, because this is an emerging field, little attention has been paid towards the suitability of different reactor types for continuous biocatalytic reactions. Two types of continuous flow reactor are possible: continuous stirred tank and continuous plug-flow. These reactor types differ in a number of ways, but in this contribution, we focus on residence time distribution and how enzyme kinetics are affected by the unique mass balance of each reactor. For the first time, we present a tool to facilitate reactor selection for continuous biocatalytic production of pharmaceuticals. From this analysis, it was found that plug-flow reactors should generally be the system of choice. However, there are particular cases where they may need to be coupled with a continuous stirred tank reactor or replaced entirely by a series of continuous stirred tank reactors, which can approximate plug-flow behavior. This systematic approach should accelerate the implementation of biocatalysis for continuous pharmaceutical production.