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Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

  • Symposium: Neutron and X-Ray Studies of Advanced Materials IV
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Abstract

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

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Acknowledgments

Diffuse scattering data for benzocaine forms I and II and aspirin form (I) were collected on the 11-ID-B beamline at the APS (Argonne, IL). Diffuse scattering data for aspirin form (II) were collected on the powder diffraction beamline at the Australian Synchrotron (Victoria, Australia). The support of the Australian Research Council, the Australian Synchrotron Research Program, and the NCI National Facility at the ANU is gratefully acknowledged. DJG gratefully acknowledges the support of the Australian Institute of Nuclear Science and Engineering. We also thank Drs. Peter Chupas and Karena Chapman, APS, and Dr. Kia Wallwork, the powder diffraction beamline of the Australian Synchrotron, for assistance with the collection of the diffuse scattering data. Use of the APS was supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.

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Authors and Affiliations

  1. Research School of Chemistry, Australian National University, Canberra, 0200, Australia

    T. R. Welberry (Professor), E. J. Chan (Postdoctoral Fellow) & A. P. Heerdegen (Research Officer)

  2. Research School of Chemistry and the Research School of Physics and Engineering, Australian National University, Canberra, 0200, Australia

    D. J. Goossens (AINSE Fellow)

Authors
  1. T. R. Welberry
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  2. E. J. Chan
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  3. D. J. Goossens
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  4. A. P. Heerdegen
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Corresponding author

Correspondence to T. R. Welberry.

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Manuscript submitted March 2, 2011.

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Welberry, T.R., Chan, E.J., Goossens, D.J. et al. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals. Metall Mater Trans A 43, 1434–1444 (2012). https://doi.org/10.1007/s11661-011-0719-7

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