Continuous manufacturing of pharmaceuticals is challenged by short campaigns due to the low volume of some products. This calls for optimization of the entire dynamic campaign to achieve the highest overall yields and productivity and to minimize waste. In this paper, we investigate how recycles could be incorporated into the design of an effective end-to-end continuous manufacturing process using nonsmooth dynamic simulation and optimization. We explore two configurations for recycle that use an organic solvent nanofiltration membrane to concentrate and recycle the mother liquor back to either the crystallizer or the reactor and find the optimal dynamic operation given a short manufacturing horizon. The campaign performance is investigated in terms of the overall yield and the on-specification productivity. It is demonstrated that recycling back to the crystallizer does increase the yield for the same overall productivity; however, recycling to the reactor significantly improves both the yield and the productivity.

• Massachusetts Institute of Technology (MIT) (MIT)

• Control

1. Control
2. dynamic simulation
3. Impurities
4. Optimization
5. Research Article
6. solvent recycle