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Pharmaceutical Research

, Volume 28, Issue 5, pp 1041–1048 | Cite as

Data Requirements for the Reliable Use of Atomic Pair Distribution Functions in Amorphous Pharmaceutical Fingerprinting

  • Timur DykhneEmail author
  • Ryan Taylor
  • Alastair Florence
  • Simon J. L. Billinge
Research Paper

ABSTRACT

Purpose

To determine the optimal measurement strategy for fingerprinting condensed phases of pharmaceutical systems using atomic pair distribution functions (PDFs) obtained from data collected using several types of x-ray diffraction instruments.

Methods

PDFs of crystalline and amorphous-phase molecular systems derived from data accessible to copper-, molybdenum-, and silver-anode laboratory sources were compared to one another and synchrotron data using qualitative and quantitative methods.

Results

We find that reliable fingerprinting is still possible using silver and molybdenum laboratory sources, but data from copper anode laboratory sources are unreliable for fingerprinting, yielding ambiguous and potentially incorrect results.

Conclusion

The ambiguities make data measured using low energy x-rays unsuitable for fingerprinting active pharmaceutical ingredients and small molecule systems, and, in general, copper anode diffractometers are undesirable for this purpose; however, laboratory x-ray sources with either Mo or Ag anodes are well suited for this application.

KEY WORDS

amorphous fingerprinting nanocrystalline pair distribution function (PDF) x-ray diffraction (XRD) 

ABBREVIATIONS

API

active pharmaceutical ingredient

PDF

pair distribution function

XRD

x-ray diffraction

TS-PDF

total scattering pair distribution function

CALS

copper-anode laboratory source

MALS

molybdenum-anode laboratory source

SALS

silver-anode laboratory source

Notes

ACKNOWLEDGMENTS

We would like to thank Pavol Juhás, Emil Božin, and Christopher Farrow for their help in collecting and analyzing the data. This work is supported through the US National Science Foundation through Grant DMR-0702940. The Advanced Photon Source is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences, under contract No. W-31-109-Eng-38.

REFERENCES

  1. 1.
    Hancock BC, Parks M. What is the solubility advantage for amorphous pharmaceuticals? Pharm Res. 2000;17(4):397–404.PubMedCrossRefGoogle Scholar
  2. 2.
    Billinge SJL, Dykhne T, Juhás P, Božin E, Taylor R, Florence AJ, et al. Characterisation of amorphous and nanocrystalline molecular materials by total scattering. CrystEngComm. 2010;12(5):1366–8.CrossRefGoogle Scholar
  3. 3.
    Bates S, Zografi G, Engers D, Morris K, Crowley K, Newman A. Analysis of amorphous and nanocrystalline solids from their x-ray diffraction patterns. Pharm Res. 2006;23(10):2333–49.PubMedCrossRefGoogle Scholar
  4. 4.
    Wright AC. Diffraction studies of glass structure: the first 70 years. Glass Phys Chem. 1998;24:148–79.Google Scholar
  5. 5.
    Egami T, Billinge SJL. Underneath the Bragg peaks: structural analysis of complex materials. Oxford: Pergamon; 2003.Google Scholar
  6. 6.
    Billinge SJL. In: Dinnebier RE, Billinge SJL, editors. Local structure from total scattering and atomic pair distribution function (pdf) analysis. Powder diffraction: theory and practice. London: Royal Society of Chemistry; 2008. p. 464–93.Google Scholar
  7. 7.
    Sheth AR, Bates S, Muller FX, Grant DJW. Polymorphism in piroxicam. Cryst Growth Des. 2004;4(6):1091–8.CrossRefGoogle Scholar
  8. 8.
    Bates S, Kelly RC, Ivanisevic I, Schields P, Zografi G, Newman AW. Assessment of defects and amorphous structure produced in raffinose pentahydrate upon dehydration. J Pharm Sci. 2007;96(5):1418–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Sheth AR, Bates S, Muller FX, Grant DJW. Local structure in amorphous phases of piroxicam from powder x-ray diffractometry. Cryst Growth Des. 2005;5(2):571–8.CrossRefGoogle Scholar
  10. 10.
    Newman A, Engers D, Bates S, Ivanisevic I, Kelly RC, Zografi G. Characterization of amorphous API:polymer mixtures using x-ray powder diffraction. J Pharm Sci. 2008;97(11):4840–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Qiu X, Thompson JW, Billinge SJL. PDFgetX2: a GUI driven program to obtain the pair distribution function from x-ray powder diffraction data. J Appl Crystallogr. 2004;37:678.CrossRefGoogle Scholar
  12. 12.
    Petkov V, Billinge SJL, Shastri SD, Himmel B. Polyhedral units and network connectivity in calcium aluminosilicate glasses from high energy x-ray diffraction. Phys Rev Lett. 2000;85:3436.PubMedCrossRefGoogle Scholar
  13. 13.
    Farrow CL, Billinge SJL. Relationship between the atomic pair distribution function and small angle scattering: implications for modeling of nanoparticles. Acta Crystallogr A. 2009;65(3):232–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Grzesiak AL, Lang M, Kim K, Matzger AJ. Comparison of the four anhydrous polymorphs of carbamazepine and the crystal structure of form i. J Pharm Sci. 2003;92(11):2260–71.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen X, Morris KR, Griesser UJ, Byrn SR, Stowell JG. Reactivity differences of indomethacin solid forms with ammonia gas. J Am Chem Soc. 2002;124(50):15012–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Cox PJ, Manson PL. Gamma-indomethacin at 120 k. Acta Crystallogr E. 2003;E59(7):o986–8.CrossRefGoogle Scholar
  17. 17.
    Chupas PJ, Qiu X, Hanson JC, Lee PL, Grey CP, Billinge SJL. Rapid acquisition pair distribution function analysis (RA-PDF). J Appl Crystallogr. 2003;36:1342–7.CrossRefGoogle Scholar
  18. 18.
    Barr G, Dong W, Gilmore CJ. Polysnap: a computer program for analysing high-throughput powder diffraction data. J Appl Crystallogr. 2004;37(4):658–64.CrossRefGoogle Scholar
  19. 19.
    Myers JL, Well AD. Research design and statistical analysis. 3rd ed. Hillsdale: Lawrence Erlbaum Associates; 2010.Google Scholar
  20. 20.
    Deslattes RD, Ernest J, Kessler G, Indelicato P, de Billy L, Lindroth E, et al. X-ray transition energies: new approach to a comprehensive evaluation. Rev Mod Phys. 2003;75(1):35–99.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Timur Dykhne
    • 1
    Email author
  • Ryan Taylor
    • 2
  • Alastair Florence
    • 2
  • Simon J. L. Billinge
    • 1
    • 3
  1. 1.Department of Applied Physics and Applied MathematicsColumbia UniversityNew YorkUSA
  2. 2.Solid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK
  3. 3.Condensed Matter Physics and Materials Science DepartmentBrookhaven National LaboratoryUptonUSA

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