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An Overview of Powder X-ray Diffraction and Its Relevance to Pharmaceutical Crystal Structures

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Analytical Techniques in the Pharmaceutical Sciences

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Single-crystal X-ray diffraction is one of the most powerful methods for the analysis of crystalline materials, but as active pharmaceutical ingredients are typically processed in the form of polycrystalline powders, powder X-ray diffraction assumes a particularly important role in their analysis. This chapter, which is targeted at pharmaceutical scientists, presents a brief introduction to the technique, before discussing the various ways in which it can be used to probe crystal structures, with a particular emphasis on the practicalities of data collection in the laboratory and on data analysis, leading ultimately to high-quality, refined crystal structures.

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Notes

  1. 1.

    A single crystal diffracts X-rays in three dimensions. A powder sample is ideally a random distribution of tiny single crystals, resulting in an orientationally averaged diffraction pattern in which reflections with identical d-spacings appear at identical 2θ values in the PXRD pattern.

  2. 2.

    This can be seen in Fig. 8.7, where the tick marks lying on the x-axis indicate the positions of reflections in the diffraction pattern.

  3. 3.

    A primary monochromator selects a particular X-ray wavelength prior to it being incident upon the sample.

  4. 4.

    Instrumental resolution is frequently quoted in terms of the ‘full width at half maximum’ (FWHM) of a reflection obtained from a very sharply diffracting standard sample, when the instrumental contribution to the observed peak width exceeds that of the sample itself.

  5. 5.

    The output of the indexing program DICVOL91 includes the following line in its text output: “WARNING: ARE YOUR DATA IRREPROACHABLE?”.

  6. 6.

    These are reflections that are predicted to appear for a unit cell with no space group symmetry, but which fail to appear in the diffraction pattern due to the effect of the underlying space group symmetry. Thus systematic absences can be used to help determine the space group symmetry.

  7. 7.

    The extinction symbol summarises the symmetry elements that are consistent with the observed systematic absences. Note that an extinction symbol can be consistent with more than one space group.

  8. 8.

    For simplicity, we will consider only Pawley refinements here, whilst noting that the closely related Le Bail method of PXRD profile fitting can be used to the same end.

  9. 9.

    The number of crystallographically independent molecules in the asymmetric unit of the unit cell.

  10. 10.

    The structural DoF for a molecular organic molecule are divided into external DoF (i.e. three positional and three orientational) and internal (i.e. the number of torsion angles that are free to rotate). Covalent bond lengths and bond angles are generally treated as fixed, well-defined quantities and so it is values for the various DoF that must be determined in order to solve the crystal structure.

  11. 11.

    Typical errors in construction of the input molecular model include the incorrect specification of chirality, cis-trans isomerism, N-atom pyramidalisation and flexible ring conformations.

  12. 12.

    Hydrogen atoms are sometimes poorly positioned in initial structure solutions, as a consequence of their weak contribution to the observed diffraction.

  13. 13.

    A free refinement is defined here as one in which the xyz coordinates of each non-H atom in the asymmetric unit of the crystal structure are free to refine as least-squares variables. Thus a 35 non-H atom structure would have 105 least-squares variables to describe the atomic positions alone.

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Acknowledgements

The author gratefully acknowledges the many long-standing collaborations that have contributed to his work in the area of PXRD, but in particular those with Bill David, Tony Csoka, Anders Markvardsen, Alastair Florence, Norman Shankland and the staff of the Cambridge Crystallographic Data Centre.

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Authors and Affiliations

  1. School of Pharmacy, University of Reading, Reading, RG6 6AD, UK

    Kenneth Shankland

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  1. Kenneth Shankland
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Correspondence to Kenneth Shankland .

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Editors and Affiliations

  1. Bioneer: FARMA Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Anette Müllertz

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, Seychelles

    Yvonne Perrie

  3. Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Thomas Rades

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Shankland, K. (2016). An Overview of Powder X-ray Diffraction and Its Relevance to Pharmaceutical Crystal Structures. In: Müllertz, A., Perrie, Y., Rades, T. (eds) Analytical Techniques in the Pharmaceutical Sciences. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-4029-5_8

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