Rapid continuous antisolvent crystallization of multi-component systems

Raza, Syed A. and Schacht, Ulrich and Svoboda, Vaclav and Edwards, Darren P. and Florence, Alastair J. and Pulham, Colin R. and Sefcik, Jan and Oswald, Iain D. H. (2018) Rapid continuous antisolvent crystallization of multi-component systems. Crystal Growth and Design, 18 (1). pp. 210-218. ISSN 1528-7483 (https://doi.org/10.1021/acs.cgd.7b01105)

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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.