Steady-state optimization of a continuous pharmaceutical process

Continuous Pharmaceutical Manufacturing can foster the production of key molecules, because it has a strong potential to improve product quality and suppress operating cost. Novel pharmaceutical production lines are thus ideal for exploring this paradigm shift, by introducing systematic process design, modern analytics and advanced control. Microreactor and microseparator engineering appears particularly advantageous in this high-value and low-capacity context, both at a pilot-plant and a full-production scale, and it can be combined with a plethora of proven continuous downstream technologies, facilitating the reduction of total organic waste emission and environmental footprint. The present paper focuses on flowsheet synthesis and optimization of an upstream process which is targeted at the production of a novel active pharmaceutical ingredient. The process flowsheet comprises four organic synthesis reactions and three separations, considering microsystems (microreactors and microseparators) for the respective steps. Conceptual synthesis allows for efficient separation and solvent integration, and indeed improves process economics, in contrast to wasteful batch pharmaceutical processing. Steady-state mass balances have been determined for the desired throughput and purity.