(212d) Continuous Millifluidic Liquid-Liquid Extraction: Digital Design and Development

Liquid-liquid extraction is a common separation technique in chemical processing. By incorporating a continuous extraction step, impurities removal can occur without the exposure of personnel to intermediates and byproducts. The inclusion of in line separation techniques allows for the integration of unit operations. In efforts to reduce the material and personnel requirements for unit operation, digital design strategies are implemented to predict extraction platform performance and determine feasible operating space. To better understand liquid- liquid extraction at the millifluidic scale, droplet analysis and fluid flow analysis was carried out to determine the type of flow regime that was observed and other parameters to assess flow conditions.

In this work, we present and implement a workflow for solvents screening and selection, batch and flow extraction experimental design, and the determination of volumetric mass transfer coefficient and digital design for extractor design for 2-chloroethyl isocyanate, ISO, a reagent in the synthesis of Lomustine. Lomustine is an anti-cancer drug that was used to treat brain tumors and Hodgkin’s Lymphoma [1]. The incorporation of the liquid-liquid extraction step in this process will allow for the continuous purification of the Lomustine intermediate prior to the second synthesis step [2].

In this study, correlations were implemented to provide predictions of the system performance beyond what was measured experimentally. Factors such as the effect of changing volume ratios on droplet size and the impact of changing residence time on volumetric mass transfer coefficient were investigated to explore the design space more fully and ultimately develop a more robust extraction process.

To our knowledge, this is the first time that this kind of analysis of the extraction parameter estimation, model selection and discrimination, and digital design for this system. The work that was conducted provide valuable tools to predict volumetric mass transfer coefficient by using dimensionless groups and the resulting extraction simulations to determine feasible operating spaces and extractor design.

1. Lee, F. Y.; Workman, P.; Roberts, J. T.; Bleehen, N. M., Clinical pharmacokinetics of oral CCNU (lomustine). Cancer Chemother. and Pharmacol. 1985, 14 (2), 125-131.
2. Jaman, Z.; Sobreira, T. J. P.; Mufti, A.; Ferreira, C. R.; Cooks, R. G.; Thompson, D. H., Rapid On-Demand Synthesis of Lomustine under Continuous Flow Conditions. Process Res. & Dev. 2019, 23 (3), 334-341.