Polymorphism on leflunomide: stability and crystal structures

J Pharm Sci. 2006 May;95(5):1075-83. doi: 10.1002/jps.20382.

Abstract

Two polymorphs of Leflunomide were found and studied (form I and II). Both of them were characterized by X-ray powder diffraction and thermal analysis. Single crystals were obtained and both structures were solved. Forms I and II crystallize in the space group P2(1)/c with two and one independent molecules per asymmetric unit, respectively. Thermodynamic stability of the two forms is assessed by differential scanning calorimetry. The cohesion in the crystal of form I (the more stable) is provided by both by H bonding as well as pi...pi interactions, while in form II it is given only by the former. The independent molecules in form I adopt different conformations thus allowing for a larger number of intermolecular interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Calorimetry, Differential Scanning
  • Crystallization
  • Drug Stability
  • Ethanol
  • Hydrogen Bonding
  • Isomerism
  • Isoxazoles / chemistry*
  • Leflunomide
  • Microscopy, Polarization
  • Models, Molecular
  • Solutions
  • Solvents
  • Spectrophotometry, Ultraviolet
  • X-Ray Diffraction

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Isoxazoles
  • Solutions
  • Solvents
  • Ethanol
  • Leflunomide