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 required multi-component 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 multi-component complexes as a test set of materials to demonstrate translation of small scale batch antisolvent crystallization to a continuous production process.