The continuous-flow production of active pharmaceutical ingredients is a spreading applicative Research Article field. Process simulation tools are effective means for in silico process design, but care is needed. A paradigmatic example is the synthesis of ibuprofen. First, the most appropriate thermodynamic models must be selected. The rich databases now available to collect thermodynamic properties are often insufficient because unconventional molecules are usually part of the recipe or found as intermediates or products. Furthermore, in some reaction steps ionic properties may be needed rather than those of the neutral molecules. All these points need a careful optimization of the methods for the estimation of the properties, with possible huge discrepancies of the results.

• University of Milan
• INSTM Unit Genova (National Interuniversity Consortium of Materials Science and Technology), Italy; University of Genoa, Italy

• API
• Modeling

1. Active pharmaceutical ingredients
2. API
3. Continuous&#8208
4. flow manufacturing
5. ibuprofen
6. microreactors
7. modeling
8. Process simulations
9. Research Article