Version 1
: Received: 9 July 2024 / Approved: 10 July 2024 / Online: 10 July 2024 (05:08:33 CEST)
How to cite:
Benmore, C. J.; Yarger, J. L.; Davidowski, S.; Shrader, C.; Smith, P.; Byrn, S. R. Hydrogen Bonding in Amorphous Indomethacin. Preprints2024, 2024070824. https://doi.org/10.20944/preprints202407.0824.v1
Benmore, C. J.; Yarger, J. L.; Davidowski, S.; Shrader, C.; Smith, P.; Byrn, S. R. Hydrogen Bonding in Amorphous Indomethacin. Preprints 2024, 2024070824. https://doi.org/10.20944/preprints202407.0824.v1
Benmore, C. J.; Yarger, J. L.; Davidowski, S.; Shrader, C.; Smith, P.; Byrn, S. R. Hydrogen Bonding in Amorphous Indomethacin. Preprints2024, 2024070824. https://doi.org/10.20944/preprints202407.0824.v1
APA Style
Benmore, C. J., Yarger, J. L., Davidowski, S., Shrader, C., Smith, P., & Byrn, S. R. (2024). Hydrogen Bonding in Amorphous Indomethacin. Preprints. https://doi.org/10.20944/preprints202407.0824.v1
Chicago/Turabian Style
Benmore, C. J., Pamela Smith and Stephen R Byrn. 2024 "Hydrogen Bonding in Amorphous Indomethacin" Preprints. https://doi.org/10.20944/preprints202407.0824.v1
Abstract
Amorphous Indomethacin has enhanced bioavailability over its’ crystalline forms, yet amorphous forms can still possess a wide variety of structures. Here, Empirical Potential Structure Refinement (EPSR) has been used to provide accurate molecular models on the structure of five different amorphous Indomethacin samples, that are consistent with their high energy x-ray diffraction patterns. It is found that the majority of molecules in amorphous Indomethacin are non-bonded or bonded to one neighboring molecule via a single hydrogen bond, in contrast the doubly bonded dimers found in the crystalline state. The EPSR models further indicate a substantial variation in hydrogen bonding between different amorphous forms, leading to a diversity of chain structures not found in any known crystal structures. The majority of hydrogen bonds are associated with the carboxylic acid group, although a significant number of amide hydrogen bonding interactions are also found in the models. Evidence of some dipole-dipole interactions are also observed in the more structurally ordered models. The results are consistent a distribution of Z-isomer intra-molecular type conformations in the more disordered structures, that dis-tort when stronger inter-molecular hydrogen bonding occurs. The findings are supported by 1H and 2H NMR studies of the hydrogen bond dynamics in amorphous Indomethacin.
Keywords
Amorphous; Pair Distribution Function; Indomethacin; X-ray diffraction; Monte Carlo simulation
Subject
Medicine and Pharmacology, Pharmacy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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