The Structure of Liquid and Glassy Carbamazepine

Chris J. Benmore, Angela Edwards, Oliver L.G. Alderman, Brian Cherry, Pamela Smith, Daniel Smith, Stephen Byrn, Richard Weber, Jeffery L. Yarger

Research output: Contribution to journalArticlepeer-review

Abstract

To enhance the solubility of orally administered pharmaceuticals, liquid capsules or amorphous tablets are often preferred over crystalline drug products. However, little is known regarding the variation in bonding mechanisms between pharmaceutical molecules in their different disordered forms. In this study, liquid and melt-quenched glassy carbamazepine have been studied using high energy X-ray diffraction and modeled using Empirical Potential Structure Refinement. The results show significant structural differences between the liquid and glassy states. The liquid shows a wide range of structures; from isolated molecules, to aromatic ring correlations and NH-O hydrogen bonding. Upon quenching from the liquid to the glass the number of hydrogen bonds per molecule increases by ~50% at the expense of a ~30% decrease in the close contact (non-bonded) carbon-carbon interactions between aromatic rings. During the cooling process, there is an increase in both singly and doubly hydrogen-bonded adjacent molecules. Although hydrogen-bonded dimers found in the crystalline states persist in the glassy state, the absence of a crystalline lattice also allows small, hydrogen-bonded NH-O trimers and tetramers to form. This proposed model for the structure of glassy carbamazepine is consistent with the results from vibrational spectroscopy and nuclear magnetic resonance.

Original languageEnglish (US)
Article number31
JournalQuantum Beam Science
Volume6
Issue number4
DOIs
StatePublished - Dec 2022

Keywords

  • amorphous
  • carbamazepine
  • glass structure
  • hydrogen bonding
  • liquid structure
  • X-ray diffraction

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Nuclear and High Energy Physics

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