Study and characterization of crystalline hydrate/polymorph forms of 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepin-6-one by solid-state NMR and solution NMR

J Pharm Biomed Anal. 2010 Apr 6;51(5):1047-53. doi: 10.1016/j.jpba.2009.11.012. Epub 2009 Nov 13.

Abstract

A novel inhibitor of reverse transcriptase was studied by solid-state NMR. Three phases of the compound were examined which included the dihydrate and two anhydrous polymorphs (Form I and Form III). By correlating (1)H and (13)C solution NMR with the solid-state (13)C NMR CP/MAS and CPPI spectral editing experiments, comparative (13)C assignments were made for each phase. Polymorphs of Form I and Form III and the dihydrate were easily distinguished based upon chemical shift patterns of the carbon resonances. The (1)H spin-lattice relaxation times were also measured for each phase which provided information on the mobility and relative crystallinity. The (13)C ssNMR spectrum of Form I showed the presence of a minor component identified as the dihydrate. Weight/percent quantitation of major and minor components in Form I was obtained from integrated intensities of a 50:50 mixture containing weighed amounts of Form I and the pure dihydrate. Comparison of the ssNMR and X-ray powder diffraction techniques is discussed.

MeSH terms

  • Azepines / chemistry*
  • Crystallization
  • Crystallography, X-Ray
  • Magnetic Resonance Spectroscopy*
  • Molecular Structure
  • Powder Diffraction
  • Pyridines / chemistry*
  • Reverse Transcriptase Inhibitors / chemistry*
  • Technology, Pharmaceutical / methods*
  • Water / chemistry

Substances

  • 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl)-6H-dipyrido(3,2-B,2',3'-E)(1,4)diazepin-6-one
  • Azepines
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • Water