Design Space Investigation for Development of Continuous Flow Syntheses of Active Pharmaceutical Ingredients

Abstract

Continuous flow chemistry and synthesis have received significant attention over the past two decades for their potential for enhancing yields, selectivities, productivities, smaller operation and implementation of otherwise difficult/dangerous reactions. Recent demonstrations applied to a variety of different reaction types have highlighted the potential for continuous manufacturing technologies for fine and speciality chemical production, including many critical Active Pharmaceutical Ingredients (APIs) but also many biopharmaceuticals and therapeutics. This study discusses recent demonstrations from the literature on design space elucidation for continuous API production and further highlights attainable regions of recoveries, material efficiencies, flowsheet complexity and cost components for upstream (reaction + separation) via modelling, simulation and nonlinear optimisation studies, providing insight into optimal regions of operation.