Continuous pharmaceutical manufacturing (CPM) has the potential to revolutionise the production of active pharmaceutical ingredients (APIs), offering operational and economic benefits over the currently dominant batch methods implemented by industry. Atropine is a nerve agent API, whose demonstrated continuous flow synthesis facilitates process modelling and optimisation. This work implements MINLP optimisation for total cost minimisation of the upstream CPM of atropine for rapid process synthesis. The process model considers reactor design from regressed reaction kinetic parameters, solute partitioning between LLE phases for different solvent systems, UNIFAC-modelled ternary liquid-liquid equilibria and mass transfer correlations for continuous LLE design. Optimisation results indicate toluene as the best (cost optimal) LLE solvent choice. This work demonstrates the utility of the described methodology for rapid process synthesis and comparative technoeconomic evaluation in early CPM process development stages.

• University of Edinburgh
• National Technical University of Athens

• API

1. API
2. Atropine
3. Continuous Pharmaceutical Manufacturing (CPM)
4. Economic analysis
5. MINLP
6. Research Article
7. Superstructure