Resource-Efficient\nSolvent Utilization: Solvent Selection\nCriteria Based on Solvent Swap Characteristics

Several solvent selection guides were developed and published\nin\nthe past, which take health, safety, and environmental aspects into\naccount. Despite their valuable contribution to more sustainable solvent\nuse in chemical manufacturing, the evaluations of these guides are\nessentially based on the characteristics of pure solvents. However,\nsince also mixtures of solvents are often handled in a multistep manufacturing\nprocess, such a pure solvent evaluation often falls short since it\ndoes not capture important process-intrinsic aspects. To improve the\npreselection of solvents, we provide in this contribution new supplemental\nprocess-related indicators which quantify the effort arising from\na solvent swap procedure considering the separability of mixtures\nof solvents. These new separation feasibility indicators (SFIs) are\nbased on calculations which not only account for real (nonideal) thermodynamic\nproperties of binary solvent mixtures but also include three key results\nof a simulated “standard” solvent swap procedure: the\nnumber of solvent swap steps needed to achieve the required purity,\nthe specific mass of lost swap solvent, and the required specific\nenergy of the solvent swap procedure. The calculations were carried\nout for 57 solvents that are commonly used in the pharmaceutical industry\nor currently discussed as “green solvents” in recent\npublications. These 57 solvents yield 1596 binary solvent mixtures\nand 3192 possible solvent swap combinations. We demonstrate with specific\nexamples that simple evaluations based on boiling point comparisons\nor relative volatilities can be misleading in the preselection of\nsolvents. The classification of solvent combinations based on the\ncalculated SFIs aids in the design of a resource-efficient manufacturing\nprocess in terms of solvent and energy consumption already at an early\nstage of process development, supporting a “first-time-right”\napproach with limited additional effort.