Investigation of the Antisolvent Effect on the Phase Behavior of Amino Acid Solid Solutions

This work focuses on the experimental measurement and modeling of solid- liquid equilibria containing continuous binary solid solutions crystallized from solvent mixtures for the usage in antisolvent crystallization. The newly constructed quaternary phase diagrams of L-valine/L-leucine in water/2-propanol and water/acetone systems are analyzed and compared to those of water/ethanol mixtures. Experimental data sets are determined via highperformance liquid chromatography, while the formation of solid solutions is confirmed with powder X-ray diffraction. Our validated modeling approach for the ternary L-valine/L-leucine/ water mixture is extended to the aforementioned quaternary systems. The modeling combines the Perturbed Chain-Statistical Associating Fluid Theory and the Non-Random Two-Liquid model to describe the liquid and solid phases, respectively. Additionally, two modeling approaches (predictive and semi-predictive) are proposed. Both models show good agreement with the experimental solubility data sets of the binary solutions. However, larger deviations were observed in three-and four-component systems, especially toward the solubility maxima. Therefore, the modeling approach should be used for qualitative initial antisolvent screenings for the separation of solid solutions using counter-current crystallization.