Solid-state 13C NMR study of indomethacin polymorphism

Int J Pharm. 2006 Aug 2;318(1-2):146-53. doi: 10.1016/j.ijpharm.2006.03.029. Epub 2006 Apr 1.

Abstract

The purpose of this study was to analyze the difference in the molecular conformation packed in the crystal lattice between the meta-stable alpha-form and stable gamma-form of indomethacin on the basis of solid-state (13)C NMR spectral patterns. The chemical shifts of each resonance of the alpha-form were distinctly different from the gamma-form. Each carbon nucleus of the gamma-form showed a single signal with no splitting. In contrast, carbon nuclei of the alpha-form showed a complicated set of resonances for each carbon. For some carbons of the alpha-form, four signals assigned to one carbon were observed at 203 K. Two of these four signals were merged between the temperature range from 203 to 343 K without a transformation in the crystal structure. It was found that solid-state (13)C NMR can be a powerful tool to estimate the number of molecular conformations as well as configurational differences in the packing of molecules in a unit cell.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Hydrogen Bonding
  • Indomethacin / chemistry*
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Temperature
  • X-Ray Diffraction

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin