Enabling direct preferential crystallization in a stable racemic compound system

Harfouche, Lina C. and Brandel, Clément and Cartigny, Yohann and Ter Horst, Joop H. and Coquerel, Gérard and Petit, Samuel (2019) Enabling direct preferential crystallization in a stable racemic compound system. Molecular Pharmaceutics, 16 (11). pp. 4670-4676. ISSN 1543-8384

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    The preparative resolution by preferential crystallization (PC) of proxyphylline has been achieved despite the existence of a stable racemic compound. This is enabled through the careful selection of a solvent in which both the racemic compound and the metastable conglomerate possess a low nucleation rate. Induction time measurements in isobutyl alcohol show that a highly supersaturated solution (β = 2.3) remains clear for almost 1 h at 20 mL scale, revealing a slow nucleation rate. Seeding the supersaturated solution with the pure enantiomer triggered its crystallization both isothermal and polythermic modes of PC were successfully implemented. Alongside the reported case of diprophylline, this study opens opportunities to broaden the application of PC toward slowly crystallizing racemic compounds.

    ORCID iDs

    Harfouche, Lina C., Brandel, Clément, Cartigny, Yohann, Ter Horst, Joop H. ORCID logoORCID: https://orcid.org/0000-0003-0118-2160, Coquerel, Gérard and Petit, Samuel;