Resource-Efficient Solvent Utilization: Solvent Selection Criteria Based on Solvent Swap Characteristics

Several solvent selection guides were developed and published in the past, which take health, safety, and environmental aspects into account. Despite their valuable contribution to more sustainable solvent use in chemical manufacturing, the evaluations of these guides are essentially based on the characteristics of pure solvents. However, since also mixtures of solvents are often handled in a multistep manufacturing process, such a pure solvent evaluation often falls short since it does not capture important process-intrinsic aspects. To improve the preselection of solvents, we provide in this contribution new supplemental process-related indicators which quantify the effort arising from a solvent swap procedure considering the separability of mixtures of solvents. These new separation feasibility indicators (SFIs) are based on calculations which not only account for real (nonideal) thermodynamic properties of binary solvent mixtures but also include three key results of a simulated "standard" solvent swap procedure: the number of solvent swap steps needed to achieve the required purity, the specific mass of lost swap solvent, and the required specific energy of the solvent swap procedure. The calculations were carried out for 57 solvents that are commonly used in the pharmaceutical industry or currently discussed as "green solvents" in recent publications. These 57 solvents yield 1596 binary solvent mixtures and 3192 possible solvent swap combinations. We demonstrate with specific examples that simple evaluations based on boiling point comparisons or relative volatilities can be misleading in the preselection of solvents. The classification of solvent combinations based on the calculated SFIs aids in the design of a resource-efficient manufacturing process in terms of solvent and energy consumption already at an early stage of process development, supporting a "first-time-right" approach with limited additional effort.