Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry

Dematos, Luciana L. and Williams, Adrian C. and Booth, Steven W. and Petts, Catherine R. and Taylor, David J. and Blagden, Nicholas (2007) Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry. Journal of Pharmaceutical Sciences, 96 (5). pp. 1069-1078. ISSN 0022-3549

Full content URL: http://dx.doi.org/10.1002/jps.20924

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Item Type:Article
Item Status:Live Archive

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. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Additional Information:23 April 2007
Keywords:2 propanol, isobutanol, methanol, nitromethane, piracetam, water, article, cross linking, crystallization, drug stability, drug structure, energy transfer, hydration, solvent effect, temperature sensitivity, thermodynamics, X ray diffraction, 2-Propanol, Butanols, Chemistry, Pharmaceutical, Crystallography, X-Ray, Kinetics, Methane, Nitroparaffins, Nootropic Agents, Phase Transition, Solvents, Synchrotrons, Technology, Pharmaceutical, Temperature, Time Factors, Water
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
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ID Code:8764
Deposited On:26 Jul 2013 09:33

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