Rapid Continuous Antisolvent Crystallization of Multicomponent Systems

This paper describes the application of a novel antisolvent crystallization approach to rapid production of tunable solid solutions of hydrophobic amino acids, comprising L-leucine, L-isoleucine, and L-valine. The antisolvent approach provides an alternative to other crystallization routes, e.g., ball milling, liquid-assisted grinding, and slurry methods, to achieve the required multicomponent solid phases. We report new crystal structures of L-leucine/L-isoleucine and L-leucine/Lvaline, and confirm a recent report on a new form of Lisoleucine/L-valine. We used these multicomponent complexes as a test set of materials to demonstrate translation of small scale batch antisolvent crystallization to a continuous production process.