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Structural characterization and aging of glassy pharmaceuticals made using acoustic levitation

Authors

  • Chris J. Benmore,

    Corresponding author
    1. X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Illinois 60439
    2. Department of Physics, Arizona State University, Tempe, Arizona 85287
    • X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Illinois 60439. Telephone: +630-2524207; Fax: +630-2524207
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  • J. K. R. Weber,

    1. X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Illinois 60439
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  • Amit N. Tailor,

    1. X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Illinois 60439
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  • Brian R. Cherry,

    1. Magnetic Resonance Research Center, Arizona State University, Tempe, Arizona 85287
    2. Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604
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  • Jeffery L. Yarger,

    1. Department of Physics, Arizona State University, Tempe, Arizona 85287
    2. Magnetic Resonance Research Center, Arizona State University, Tempe, Arizona 85287
    3. Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604
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  • Qiushi Mou,

    1. Department of Physics, Arizona State University, Tempe, Arizona 85287
    2. Magnetic Resonance Research Center, Arizona State University, Tempe, Arizona 85287
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  • Warner Weber,

    1. Magnetic Resonance Research Center, Arizona State University, Tempe, Arizona 85287
    2. Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604
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  • Joerg Neuefeind,

    1. Spallation Neutron Source, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37922
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  • Stephen R. Byrn

    1. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907
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Abstract

Here, we report the structural characterization of several amorphous drugs made using the method of quenching molten droplets suspended in an acoustic levitator. 13C NMR, X-ray, and neutron diffraction results are discussed for glassy cinnarizine, carbamazepine, miconazole nitrate, probucol, and clotrimazole. The 13C NMR results did not find any change in chemical bonding induced by the amorphization process. High-energy X-ray diffraction results were used to characterize the ratio of crystalline to amorphous material present in the glasses over a period of 8 months. All the glasses were stable for at least 6 months except carbamazepine, which has a strong tendency to crystallize within a few months. Neutron and X-ray pair distribution function analyses were applied to the glassy materials, and the results were compared with their crystalline counterparts. The two diffraction techniques yielded similar results in most cases and identified distinct intramolecular and intermolecular correlations. The intramolecular scattering was calculated based on the crystal structure and fit to the measured X-ray structure factor. The resulting intermolecular pair distribution functions revealed broad-nearest and next-nearest neighbor molecule–molecule correlations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1290–1300, 2013

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