The phase relationship between the pyrazinamide polymorphs α and γ.
Int J Pharm
; 580: 119230, 2020 Apr 30.
Article
en En
| MEDLINE
| ID: mdl-32199962
Pyrazinamide is an active pharmaceutical compound for the treatment of tuberculosis. It possesses at least four crystalline polymorphs. Polymorphism may cause solubility problems as the case of ritonavir has clearly demonstrated; however, polymorphs also provide opportunities to improve pharmaceutical formulations, in particular if the stable form is not very soluble. The four polymorphs of pyrazinamide constitute a rich system to investigate the usefulness of metastable forms and their stabilization. However, despite the existence of a number of papers on the polymorphism of pyrazinamide, well-defined equilibrium conditions between the polymorphs appear to be lacking. The main objectives of this paper are to establish the temperature and pressure equilibrium conditions between the so-called α and γ polymorphs of pyrazinamide, its liquid phase, and vapor phase and to determine the phase-change inequalities, such as enthalpies, entropies, and volume differences. The equilibrium temperature between α and γ was experimentally found at 392(1) K. Moreover, vapor pressures and solubilities of both phases have been determined, clearly indicating that form α is the more stable form at room temperature. High-pressure thermal analysis and the topological pressure-temperature phase diagram demonstrate that the γ form is stabilized by pressure and becomes stable at room temperature under a pressure of 260 MPa.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazinamida
Idioma:
En
Revista:
Int J Pharm
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos