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Transformations between Co-Amorphous and Co-Crystal Systems and Their Influence on the Formation and Physical Stability of Co-Amorphous Systems

  • Wenqi Wu
    Wenqi Wu
    Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    More by Wenqi Wu
  • Yixuan Wang
    Yixuan Wang
    Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Rd. 103, Shenyang 110016, China
    More by Yixuan Wang
  • Korbinian Löbmann
    Korbinian Löbmann
    Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
  • Holger Grohganz
    Holger Grohganz
    Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
  • , and 
  • Thomas Rades*
    Thomas Rades
    Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20521 Turku, Finland
    *E-mail: [email protected]
    More by Thomas Rades
Cite this: Mol. Pharmaceutics 2019, 16, 3, 1294–1304
Publication Date (Web):January 9, 2019
Copyright © 2019 American Chemical Society

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    The formation of co-amorphous and co-crystal systems are attractive formulation strategies for poorly water-soluble drugs. Intermolecular interactions between the drug and the coformer(s) play an important role in the formation of both systems, making the investigation of transformations between the two systems specifically interesting. The aim of this study thus was to investigate the transformation between the two systems and its influence on the formation and physical stability of co-amorphous systems. Carbamazepine (CBZ) along with benzoic acid, maleic acid, succinic acid, tartaric acid, saccharin, and nicotinamide were used as materials. First, CBZ–co-former co-crystals were prepared. Then the co-crystals and CBZ–co-former physical mixtures were ball milled to investigate the possible co-amorphization process. The XRPD and DSC results showed that CBZ and coformers tended to maintain (co-crystals as the starting material) or form co-crystals (physical mixtures as the starting material), rather than to form co-amorphous systems. Next, co-amorphization from CBZ–co-former physical mixtures via quench cooling was studied. While co-amorphous systems were obtained, the physical stability of these was very low, and the samples recrystallized to either co-crystal forms or the individual components. In conclusion, a possible transformation between the two systems was confirmed, but the resulting co-amorphous systems were highly unstable.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.molpharmaceut.8b01229.

    • Thermograms of physical mixture samples and co-crystals; XRPD diffractograms of the starting and ball milled co-crystals, CBZ–co-former physical mixtures, and crystalline CBZ after different milling times; DSC thermograms of ball milled CBZ–co-former samples; thermograms of quench cooled CBZ–co-former samples; XRPD diffractograms of amorphous CBZ after storage at 40 °C under dry condition; and FTIR spectra of CBZ–SUC systems and CBZ–NIC systems (PDF)

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