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    Solvent influences on Metastable Polymorph Lifetimes:Real-time interconversions using Energy Dispersive X-Ray Diffractometry

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    Publication date
    2007
    Author
    Blagden, Nicholas
    Booth, S.W.
    De Matos, Luciana L.
    Williams, Adrian C.
    Keyword
    Polymorph
    Synchrotron
    Hydrate
    Transformation
    Crystal Growth
    Piracetam
    In Situ Crystallisation
    Solvent Effects
    Energy Dispersive X-ray Diffraction
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Solvent influences on the crystallization of polymorph and hydrate forms of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth profiles of piracetam polymorphs were constructed using time-resolved diffraction snapshots collected for each solvent system. Measurements were performed by in situ energy dispersive X-ray diffraction recorded in Station 16.4 at the synchrotron radiation source (SRS) at Daresbury Laboratory, CCLRC UK. Crystallizations from methanol, 2-propanol, isobutanol, and nitromethane progressed in a similar fashion with the initial formation of form I which then converted relatively quickly to form II with form III being generated upon further cooling. However, considerable differences were observed for the polymorphs lifetime and both the rate and temperature of conversion using the different solvents. The thermodynamically unstable form I was kinetically favored in isobutanol and nitromethane where traces of this polymorph were observed below 10°C. In contrast, the transformation of form II and subsequent growth of form III were inhibited in 2-propanol and nitromethane solutions. Aqueous solutions produced hydrate forms of piracetam which are different from the reported monohydrate; this crystallization evolved through successive generation of transient structures which transformed upon exchange of intramolecular water between the liquid and crystalline phases
    URI
    http://hdl.handle.net/10454/4120
    Version
    No full-text available in the repository
    Citation
    Blagden, N., Booth, S.W., DeMatos, L.L. and Williams, A.C. (2007). Solvent influences on Metastable Polymorph Lifetimes:Real-time interconversions using Energy Dispersive X-Ray Diffractometry. Journal of Pharmaceutical Sciences. Vol. 96, No. 5, pp. 1069-1078.
    Link to publisher’s version
    http://dx.doi.org/10.1002/jps.20924
    Type
    Article
    Collections
    Life Sciences Publications

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