Data Requirements for the Reliable Use of Atomic Pair Distribution Functions in Amorphous Pharmaceutical Fingerprinting
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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.
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.
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.
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 WORDSamorphous fingerprinting nanocrystalline pair distribution function (PDF) x-ray diffraction (XRD)
active pharmaceutical ingredient
pair distribution function
total scattering pair distribution function
copper-anode laboratory source
molybdenum-anode laboratory source
silver-anode laboratory source
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.
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