Systematic nonlinear optimisation is a valuable tool towards evaluating the performance of conceptual Continuous Pharmaceutical Manufacturing (CPM) flowsheets. This study considers total cost minimisation of multiple plausible design choices and eight candidate antisolvents for the continuous recovery of artemisinin (a potent antimalarial Active Pharmaceutical Ingredient/API) via continuous crystallisation, with simultaneous evaluation of process mass and environmental efficiency via the E-factor (an established green chemistry metric). Essential design variables include the crystallisation cooling temperature, the antisolvent requirements and the use of multiple crystallisers in series. Acetonitrile achieves the minimum total cost for one crystalliser (761.10(3) GBP, for a crystallisation at 5 degrees C, with 80% antisolvent addition and an E-factor of 29.1). The use of a second crystalliser in series allows for further total cost savings for all antisolvents; E-factors continue to decrease accordingly, albeit with very limited scope for each successive crystalliser due to negligible productivity improvements. (C) 2017 Elsevier Ltd. All rights reserved.

• University of Edinburgh

• API

1. API
2. Artemisinin
3. Continuous Pharmaceutical Manufacturing (CPM)
4. crystallisation
5. Nonlinear Programming (NLP)
6. Optimization
7. Research Article
8. solvent selection