Process Modeling Issues in the Design of a Continuous-Flow Process for the Production of Ibuprofen

The continuous-flow production of active pharmaceutical ingredients is a spreading applicative research 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.