Pharmaceutical phase equilibria and the polymorphism of pyrazinamide
Ivo Rietveld
University of Rouen
https://tugraz.webex.com/tugraz/j.php?MTID=m0e9edf6219fdb613ef773c7469631445
11:15 - 12:15 Wednesday 13 December 2023 Phase equilibria are considered a thing of the past since "Phase Theory" has been published by J.W. Gibbs 150 years ago. However, the richness in possibilities to control pharmaceutical formulations and on the other hand the delicate task of ensuring the stability of such formulations require a profound understanding of the phase behaviour of molecular compounds and of their interactions.
The presentation will briefly introduce thermodynamic stability and its importance in the pharmaceutical solid state. The importance will be highlighted by the example of pyrazinamide, a drug against tuberculosis, which possesses at least four polymorphs: alpha, beta, gamma, and delta.
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.
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Institute of Solid State Physics
