Continuous Pharmaceutical Manufacturing (CPM) has a strong potential to catalyse pharmaceutical innovation. This paper analyses Continuous Oscillatory Baffled Crystalliser (COBC) optimal design and performance for paracetamol crystallisation, via systematic modelling and nonlinear optimization (NLP). Clear trends emerge, with rate of antisolvent use having a marked impact on COBC volumes; crystal seed mass loading also has a strong effect. For the base case studied (inlet temperature of 50 degrees C, seed crystal size of 40 mu m) the optimal operation has been determined to be under using 2% seed mass loading (with respect to solute mass) and with 80% water antisolvent use (by mass with respect to process solvent acetone); the crystalliser size required has been computed equal to 4.25 L with a total cost of 101,370 GBP, achieving a product yield of 50% with a product crystal size of 83.6 mu m. Clear trade-offs among mass efficiency, volume, cost and product crystal size have been illustrated, providing valuable quantitative insights into process performance. (C) 2018 Elsevier Ltd. All rights reserved.

• University of Edinburgh

• API

1. API
2. COBC
3. Crystallization process
4. Crystal size
5. Oscillatory baffled crystallizer
6. paracetamol
7. Research Article