title: The topological pressure-temperature phase diagram of ritonavir, an extraordinary case of crystalline dimorphism.
abstract: A topological pressure-temperature phase diagram involving the phase relationships of ritonavir forms I and II has been constructed using experimental calorimetric and volumetric data available from the literature. The triple point I-II-liquid is located at a temperature of about 407 K and a pressure as extraordinarily small as 17.5 MPa (175 bar). Thus, the less soluble solid phase (form II) will become metastable on increasing pressure. At room temperature, form I becomes stable around 100 MPa indicating that form II may turn into form I at a relatively low pressure of 1000 bar, which may occur under processing conditions such as mixing or grinding. This case is a good example for which a proper thermodynamic evaluation trumps "rules of thumb" such as the density rule.
authors.affiliation: Caractérisation des matériaux moléculaires à activité thérapeutique (CAMMAT), faculté de pharmacie, 4, avenue de l'Observatoire, 75006 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Céolin
authors.affiliation: Caractérisation des matériaux moléculaires à activité thérapeutique (CAMMAT), faculté de pharmacie, 4, avenue de l'Observatoire, 75006 Paris, France. Electronic address: ivo.rietveld@parisdescartes.fr.
authors.forename: I B
authors.initials: IB
authors.lastname: Rietveld
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004304:Dosage Forms; D004355:Drug Stability; D011312:Pressure; D019438:Ritonavir / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D019380:Anti-HIV Agents; D004304:Dosage Forms; D019438:Ritonavir
keywords: Crystalline polymorphism; Diagramme P-T topologique; Polymorphisme cristallin; Ritonavir; Stabilité thermodynamique; Thermodynamic stability; Topological P-T diagram