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    Computational predictions of glass-forming ability and crystallization tendency of drug molecules.

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    Authors
    Alhalaweh, Amjad
    Alzghoul, Ahmad
    Kaialy, Waseem
    Mahlin, Denny
    Bergström, Christel A S
    Issue Date
    2014-07-30
    
    Metadata
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    Abstract
    Amorphization is an attractive formulation technique for drugs suffering from poor aqueous solubility as a result of their high lattice energy. Computational models that can predict the material properties associated with amorphization, such as glass-forming ability (GFA) and crystallization behavior in the dry state, would be a time-saving, cost-effective, and material-sparing approach compared to traditional experimental procedures. This article presents predictive models of these properties developed using support vector machine (SVM) algorithm. The GFA and crystallization tendency were investigated by melt-quenching 131 drug molecules in situ using differential scanning calorimetry. The SVM algorithm was used to develop computational models based on calculated molecular descriptors. The analyses confirmed the previously suggested cutoff molecular weight (MW) of 300 for glass-formers, and also clarified the extent to which MW can be used to predict the GFA of compounds with MW < 300. The topological equivalent of Grav3_3D, which is related to molecular size and shape, was a better descriptor than MW for GFA; it was able to accurately predict 86% of the data set regardless of MW. The potential for crystallization was predicted using molecular descriptors reflecting Hückel pi atomic charges and the number of hydrogen bond acceptors. The models developed could be used in the early drug development stage to indicate whether amorphization would be a suitable formulation strategy for improving the dissolution and/or apparent solubility of poorly soluble compounds.
    Citation
    Computational predictions of glass-forming ability and crystallization tendency of drug molecules. 2014, 11 (9):3123-32 Mol. Pharm.
    Publisher
    ACS Publications
    Journal
    Molecular pharmaceutics
    URI
    http://hdl.handle.net/2436/562213
    DOI
    10.1021/mp500303a
    PubMed ID
    25014125
    Type
    Journal article
    Language
    en
    ISSN
    1543-8392
    ae974a485f413a2113503eed53cd6c53
    10.1021/mp500303a
    Scopus Count
    Collections
    Research Institute in Healthcare Science

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