Pyrazinamide, an API with four polymorphs. When are they stable?

  • Crystallization
  • 24 January 2023

About the webinar

A webinar organized together with speaker Dr. Ivo Rietveld - Lecturer (HDR) at Université de Rouen and Associate professor at Université Paris Descartes. 


The webinar focused on the phase behaviour of drug molecules, and why it is important to control the desired polymorph in drug formulations. The aim can be to ensure better stability of the formulation or better solubility (solubilization) of the drug. It also showcased pyrazinamide, a drug against tuberculosis, with four polymorphs and their polymorphic interdependence.


Stability studies of this active pharmaceutical ingredient have been complicated due to the very slow transition kinetics observed in DSC measurements. Using vapour pressure measurements, in which the reluctance of phase transformation is in fact an advantage, all solid-solid phase transformation temperatures have been determined. This method has been key to map the phase behaviour of pyrazinamide. The use of high-pressure measurements with synchrotron X-ray diffraction at several temperatures from room temperature up to 120 °C has allowed to construct the pressure-temperature phase diagram of the four solid phases of pyrazinamide and the liquid phase.

The a form was found to be the stable form at room temperature and unexpectedly even the b form is stable at very low temperatures.

Pyrazinamide, an API with four polymorphs. When are they stable

Guest speaker

Ivo Rietveld

Lecturer, University of Rouen

Dr. Ivo Rietveld has obtained his PhD on the physical properties of dendrimers in 2000 at the University of Leiden. He has carried out post-doctoral research on electrospray of water at the University of Delft and in 2001 and 2002 he worked as a post-doctoral researcher at the University of Pennsylvania on dendrimer protected porphyrins to measure the oxygen content in blood and tissue.

From 2003 to 2007, he worked at the University of Kyoto on the fabrication of thin ferroelectric polymer films by electrospray. In 2007, he was hired as an assistant professor at the Faculty of Pharmacy of the University Paris Descartes with as main research subject the thermodynamic stability of active pharmaceutical ingredients in which he is still active as an associate professor. In 2017, he became a member of the SMS laboratory at the University of Rouen.

His research subjects cover: thermodynamic stability, resolution of enantiomer mixtures, crystallisation and the stabilisation of metastable forms such as amorphous mixtures and metastable polymorphs.