(657b) Use of Simulation to Raise Awareness of the Sustainability Potential of Solvent Exchange Distillations

In the pharmaceutical industry, sustainability and green chemistry initiatives frequently focus on reducing the overall mass of material used to produce APIs as a broad indicator of environmental impact. Several benchmarking studies have noted that solvents are majority contributors to the mass utilization, process mass intensity (PMI), for a typical batch process of pharmaceutical [1, 2], as well as process costs. Frequently, multiple solvents are required in a process to facilitate specific unit operations, and solvent exchange distillations are used to remove and replace one solvent with another. We believe solvent exchange distillations represent a unique opportunity for significant sustainability improvements across the industry due to their prevalence, commonalities, and potential for improvements to solvent and energy usage.

Since distillations in the pharmaceutical processing typically occur at mild pressures, in dilute solutions, and with similar solvents, process simulations can often be broadly applied, accurate, and facilitate optimal design with few experiments. In this work, we applied Dynochem and RunScript Automation software to automate and optimize simulations of a broad range of solvent exchange distillations. We explored the mode of operation and distillation parameters, such as volume constraints, pressure, and relative volatility, and the impact on sustainability results, such as solvent and energy usage. Furthermore, a deployable web app was developed that can be shared with the broader community to apply this approach and quickly characterize the sustainability impact of the distillation design. We hope this work will bring greater awareness of the sustainability potential of solvent exchange distillations and encourage the use of process modelling to design every such process to trigger sustainabaility benefits.

[1] Jimenez-Gonzalez C, Ponder CS, Broxterman QB, and Manley JB. Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry To Drive More Sustainable Processes. Org. Process Res. Dev. 2011 15 (4), 912-917.

[2] Constable DJC, Jimenez-Gonzalez C, Henderson RK. Perspective on solvent use in the pharmaceutical industry. Org. Process Res. Dev., 2007 11 (1), 133-137.