Rapid continuous antisolvent crystallization of multi-component 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/l-valine, and confirm a recent report on a new form of l-isoleucine/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.