Polymorphic behavior of an NK1 receptor antagonist

Int J Pharm. 2002 Aug 28;243(1-2):147-59. doi: 10.1016/s0378-5173(02)00292-2.


Four anhydrous polymorphic forms (I, II, III and IV) of an NK1 receptor antagonist, Compound A, have been discovered. The pure compound can exist as either Forms I or II at room temperature and Forms III or IV at elevated temperatures. The four polymorphs were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis, X-ray powder diffraction (XRPD) and solid-state NMR spectroscopy (SSNMR). Polymorphic transformations in the solid phase were studied using DSC, hot stage XRPD, temperature-modulated SSNMR and hot stage optical microscopy. The solubilities of Forms I and II in tert-butyl acetate at different temperatures were measured and the relative stability of the two forms was established. The thermodynamic transformation temperatures between Forms I and III, as well as Forms II and IV, were estimated by DSC. Transformation from Form III to IV, which is undetectable in a normal calorimetric run, was revealed through careful thermal programming. An interesting conversion route from Form I, a more stable form at room temperature, to Form II, a less stable form at room temperature was discovered.

MeSH terms

  • Calorimetry, Differential Scanning
  • Crystallography, X-Ray
  • Magnetic Resonance Spectroscopy
  • Morpholines / chemistry*
  • Neurokinin-1 Receptor Antagonists*
  • Solubility
  • Temperature
  • Thermogravimetry
  • Triazoles / chemistry*


  • 1-(5-((2-((1-(3,5-bis(trifluoromethyl)phenyl)ethyl)oxy)-3-(4-fluorophenyl)morpholin-4-yl)methyl)-2H-1,2,3-triazol-4-yl)-N,N-dimethylmethanamine
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Triazoles