Solid-state characterization of an NR2B selective N-methyl d-aspartate (NMDA) antagonist polymorphs

Int J Pharm. 2008 May 1;355(1-2):337-40. doi: 10.1016/j.ijpharm.2007.11.060. Epub 2007 Dec 7.

Abstract

(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-piperidin-1-yl]-1-hydroxyethyl]-3,4-dihydro-quinolin-2(1H)-one (compound A) is an NR2B selective N-methyl d-aspartate (NMDA) antagonist that has shown at least two polymorphs, forms I and II. In this report, we prepared two polymorphs, forms I and II and their crystal forms were identified and characterized by single crystal X-ray diffractometry, differential scanning calorimetry (DSC) and variable temperature powder X-ray diffractometry (VT-PXRD). The results of DSC and VT-PXRD suggested that compound A has at least three polymorphic forms: I, II and a new form III, and that forms II and III showed an enantiotropic relationship. We also performed single crystal X-ray analyses of specific conditions based on the results of VT-PXRD. The unit cell dimensions in crystallographic parameter and molecular arrangements of form I were quite different from forms II and III. Whereas, the crystal structures of forms II and III were similar with the exception of the C58-C59-C61-C62 torsion angle.

MeSH terms

  • Excitatory Amino Acid Antagonists / pharmacology*
  • Isomerism
  • Microscopy, Electron, Scanning
  • Models, Molecular
  • Molecular Conformation
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • X-Ray Diffraction

Substances

  • 6-(2-(4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl)-1-hydroxyethyl)-3,4-dihydro-2(1H)-quinolinone
  • Excitatory Amino Acid Antagonists
  • NR2B NMDA receptor
  • Piperidines
  • Quinolones
  • Receptors, N-Methyl-D-Aspartate