Advantages of SR-XRPD

Solid state forms of complex molecular structures have diffraction patterns characterized by many and overlapped reflections. In such cases, data interpretation can be quite demanding and explains why for many years XRPD has been almost uniquely employed as a fingerprinting technique, both for qualitative and quantitative assessments.

During the last 10-15 years, an impressive development in instrumentation, computer technology and powder diffraction experimental techniques [13,14] and methodologies [15-22] took place, which upgraded XRPD from a support technique to a fundamental one. Furthermore, the recent development of total scattering techniques (i.e. techniques that interpret both Bragg and diffuse elastic scattering) has extended the use of powder diffraction to nano- or non-crystalline (i.e. liquid and amorphous) materials [23-25].


SR-XRPD has major advantages over laboratory XRPD


  • High photon wavelength resolution (∆λ/λ better than 2.10-4)
  • Highly collimated (residual divergence less than 20 μrad) and intense (> 1013photon/sec) photon beam
  • Tunable photon energy ideal to perform anomalous scattering experiments, collect fluorescence-free XRPD data and better diffraction peaks separation.
  • Angular (FWHM) resolution better than 0.01° 2θ obtained with new generation solid state microstrip detectors (e.g. MYTHEN II detector developed at the Swiss Light Source and available to Excelsus) and down to 0.002° 2θ using multicrystal analyser detectors
  • d-spacing resolution better than 0.35 Ǻ
  • Millions count counting statistics in reflection (Bragg-Brentano) as well as in transmission (Debye-Scherrer) modes even with low quantities of powder available
  • Reduced preferential orientation effects due to transmission geometry and very high-frequency sample spinning (>10 Hz)
  • Ultra-fast data acquisition (milliseconds scale) for efficient, dose-controlled and time-resolved XRPD
  • Very high signal-to-noise and signal-to-background
  • Very high counting statistics (millions of counts) in seconds/minutes




In conclusion


Laboratory XRPD is suitable for routine and structural analyses of medium difficulty. However, the identification of polymorphs with similar structure, their quantification in complex mixtures or the detection of low levels of impurities (less than a few %) require SR-XRPD.

The experimental artefacts that characterize laboratory XRPD prevent it in such cases to ascertain the structural and microstructural properties of pharmaceutical compounds [4, 22, 23]. Furthermore, SR-XRPD allows the detection of unexpected structural changes or unknown forms during manufacturing conditions, e.g. in the field of pharmaceuticals, kinetic studies at the msec scale and the application of XRPD to more complex systems, e.g. biologicals molecules.



  1. Bish, DL and Post, JE, editors. 1989. Modern Powder Diffraction. Reviews in Mineralogy, Vol. 20. Mineralogical Society of America
  2. Cullity, B. D. 1978. Elements of X-ray diffraction. 2nd ed. Addison-Wesley, Reading, Mass
  3. I. Ivanisevic, R. B. McClurg and P. J. Schields: Uses of X-Ray Powder Diffraction in the Pharmaceutical Industry, Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development and Manufacturing, Ed. by Shayne C. Gad., p. 1-42 (2010).
  4. S. R. Byrn, S. Bates and I. Ivanisevic: Regulatory Aspects of X-ray Powder Diffraction, Part 1, American Pharmaceutical Review, p.55-59 (2005).
  5. D. Beckers: The power of X-ray analysis, Pharmaceutical Technology Europe (2010), p.29,30.
  6. M. Sakata, S. Aoyagi, T. Ogura & E. Nishibori (2007): Advanced Structural Analyses by Third Generation Synchrotron Radiation Powder Diffraction, AIP Conference Proceedings, Vol. 879, pp. 1829-1832 (2007).
  7. Bergamaschi, A.; Cervellino, A.; Dinapoli, R.; Gozzo, F.; Henrich, B.; Johnson, I.; Kraft, P.; Mozzanica, A.; Schmitt, B.; Shi, X.: The MYTHEN detector for X-ray powder diffraction experiments at the Swiss Light Source. J. Synchrotron Rad. 17 (2010) 653–668.
  8. R.B. Von Dreele, P.W. Stephens, G.D. Smith, and R.H. Blessing: The First Protein Crystal Structure Determined from X-ray Powder Diffraction Data: a Variant of T3R3 Human Insulin Zinc Complex Produced by Grinding,Acta Cryst. D 56, 1549-53 (2000).
  9. Margiolaki, I., Wright, J. P., Fitch, A. N., Fox, G. C. & Von Dreele, R. B.: Synchrotron X-ray powder diffraction study of hexagonal turkey egg-white lysozyme, Acta Cryst. D61, 423–432 (2005). See also: Margiolaki, I. & Wright, J. P.: Powder crystallography on macromolecules, Acta Cryst. A64, 169–180 (2008).
  10. Fundamentals of Crystallography,C. Giacovazzo Ed., International Union of Crystallography, Oxford Science Publications, Third Edition (2011).
  11. The basics of Crystallography and Diffraction (Third edition, 2010), Christopher Hammond, IUCr, Oxford Science Publications; ISBN 978-0-19-954645-9. See also: X-Ray Structure Determination, A practical Guide, George H. Stout and Lyle H. Jensen, Wiley Interscience.
  12. Bruni G, Gozzo F, Capsoni D, Bini M, Macchi P, Simoncic P, Berbenni V., Milanese C., Girella A., Ferrari S. and Marini A., Thermal, Spectroscopic, and Ab Initio Structural Characterization of Carprofen Polymorphs, J. Pharm. Sciences 100(6), 2321 (2011).
  1. Brunelli, M., Wright, J. P., Vaughan, G. B. M., Mora, A. J. & Fitch, A. N.: Solving Larger Molecular Crystal Structures from Powder Diffraction Data by Exploiting Anisotropic Thermal Expansion. Angew. Chem. (2003) 115, 2075–2078.
  2. T. Wessels, Ch. Baerlocher and L.B. McCusker: Single-crystal-like diffraction data from polycrystalline materials, Science (1999), 284, 477-479.
    Shankland, K., David, W. I. F., Csoka, T. & McBride, L.: Structure solution of Ibuprofen from powder diffraction data by the application of a genetic algorithm combined with prior conformational analysis, Intl. J. Pharmaceut. (1998) 165, 117–126.
  3. A. Altomare, C. Cuocci, C. Giacovazzo, A. Moliterni and R. Rizzi: The dual-space resolution bias correction algorithm: applications to powder data, J. Appl. Cryst. (2010). 43, 798-804.
    G.Oszlanyi and A. Suto: The charge flipping algorithm, Acta Cryst. (2008). A64, 123–134 and references herein.
  4. Boccaleri, E., Carniato, F., Croce, G., Viterbo, D., van Beek, W., Emerich H. and Milanesio, M., In-situ simultaneous Raman/high-resolution X-ray powder diffraction study of transformations occurring in materials at non-ambient conditions, J. Appl. Cryst., 2007, 40, 684-693.
  5. Scarlett N.V.Y. and Madsen I. C., Quantification of phases with partial or no known crystal structures, Powder Diffraction (2006) 21, 278-284
    Giannini C., Guagliardi A. and Millini R., Quantitative phase analysis by combining the Rietveld and the whole-pattern decomposition methods, J. Appl. Cryst., 2002, 35, 481-490.
  6. Scardi, P.; Leoni, M.: Line profile analysis: pattern modeling versus profile fitting, J. Appl. Cryst. 39 (2006) 24–31. Scardi, P.; Leoni, M.: Whole Powder Pattern Modelling, Acta Crystall. A58 (2002) 190–200
  7. Local structure from total scattering and atomic pair distribution function (PDF) analysis, In Powder diffraction: theory and practice, (Royal Society of Chemistry, London England, 2008), Robert E. Dinnebier and Simon J. L. Billinge, Eds., pp. 464 – 493.
  8. Neder R. B. And Korsunskiy V. I., Structure of nanoparticles from powder diffraction data using the pair distribution function, 2005 J. Phys.: Condens. Matter 17 S125
  9. A. Cervellino, C. Giannini, A. Guagliardi, Determination of nanoparticle, size distribution and lattice parameter from x-ray data for monoatomic materials with f.c.c. cubic unit cell, J. Appl. Cryst. 36, 1148-1158 (2003).
  10. P.W. Stephens, D.E. Cox, and A.N. Fitch, Synchrotron Radiation Powder Diffraction in Structure Determination by Powder Diffraction, pp. 49-87, edited by W.I.F. David, K.
    Shankland, L.B. McCusker, and C. Baerlocher, (Oxford University Press, 2002)
  11. Joel Bernstein: Polymorphism in Molecular Crystals, IUCr Monographs on Crystallography (2002), Oxford Science Publications.
    Polymorphism in Pharmaceutical Solids, Ed. By Harry G. Brittain, Drugs and The Pharmaceutical Sciences, Vol. 192
  12. Tremayne, M.: The impact of powder diffraction on the structural study of organic materials., Philosophical Transactions of the Royal Society of London Series A: Chemistry and Life Sciences Triennial Issue, 362: 2691 (2004).
  13. Law D, Schmitt EA, Marsh KC, Everitt EA,Wang W, Fort JJ, Krill SL, Qiu Y. Ritonavir-PEG 8000 amorphous solid dispersions: in vitro and in vivo evaluations. J. Pharm. Sci. 2004; 93 (3): 563–567.
  14. Bruni G., Berbenni V., Milanese C., Girella A., Cardini A., Lanfranconi S. and Marini A., Determination of the nateglinide polymorphic purity through DSC, J. Pharm. and Biomed. Anal. 54 (2011) 1196-1199.
  15. Aaltonen J., Alleso M., Mirza S., Koradia V., Gordon K.C and Rantanen J., Solid form screening – A review. European Journal of Pharmaceutics and Biopharmaceutics 71 (2009), 23-37.
    Srivastava D., The Food and Drug Administration and Patent Law at a Crossroads: The Listing of Polymorph Patents as a Barrier to Generic Drug Entry. Food and Drug Law Journal, Vol. 59, No.2 (2004), 339-354.
  16. Grabowski H. G., Kyle M., Mortimer R., Long G. & Kirson N., Evolving Brand-name And Generic Drug Competition May Warrant A Revision Of The Hatch-Waxman Act. Health Affairs, 30, no.11 (2011):2157-2166.
  17. Rakowski W. A and Mazzochi D. M., The case of disappearing polymorph: 'Inherent anticipation' and the impact of Smithkline Beecham Corp. v Apotex Corp. (Paxil®) on patent validity and infringement by inevitable conversion'. Journal of Generic Medicine, Vol.1, No.2 (2006):131-139.
  18. Cabri W., Ghetti P., Pozzi G. and Alpegiani M., Polymorphisms and Patent, Market, and Legal Battles: Cefdinir Case Study. Organic Process Research & Development 2007, 11, 64-72.
    Bauer J, Spanton S, Henry R, Quick J, Dziki W, Porter W, Morris J., Ritonavir: an extraordinary example of conformational polymorphism, Pharm Res. 2001 Jun;18(6):859-66.
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