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 (https://doi.org/10.1021/acs.molpharmaceut.9b00805)

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Abstract

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;
  • Item type:Article
    ID code:72792
    Dates:
    Date
    Event
    4 November 2019
    Published
    23 September 2019
    Published Online
    23 September 2019
    Accepted
    Notes:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work seehttps://doi.org/10.1021/acs.molpharmaceut.9b00805
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:18 Jun 2020 09:39
    Last modified:11 Nov 2024 12:28
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/72792
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