title: Stability hierarchy between Piracetam forms I, II, and III from experimental pressure-temperature diagrams and topological inferences.
abstract: The trimorphism of the active pharmaceutical ingredient piracetam is a famous case of polymorphism that has been frequently revisited by many researchers. The phase relationships between forms I, II, and III were ambiguous because they seemed to depend on the heating rate of the DSC and on the history of the samples or they have not been observed at all (equilibrium II-III). In the present paper, piezo-thermal analysis and high-pressure differential thermal analysis have been used to elucidate the positions of the different solid-solid and solid-liquid equilibria. The phase diagram, involving the three solid phases, the liquid phase and the vapor phase, has been constructed. It has been shown that form III is the high-pressure, low-temperature form and the stable form at room temperature. Form II is stable under intermediary conditions and form I is the low pressure, high temperature form, which possesses a stable melting point. The present paper demonstrates the strength of the topological approach based on the Clapeyron equation and the alternation rule when combined with high-pressure measurements.
authors.affiliation: Laboratoire de Chimie Physique et Chimie Minérale, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'observatoire, 75006 Paris, France; Département de Chimie-UMR 6226, Faculté des Sciences, Université de Rennes 1, Bâtiment 10B, 263, Avenue du Général Leclerc, 35042 Rennes Cedex, France.
authors.forename: Siro
authors.initials: S
authors.lastname: Toscani
authors.affiliation: Laboratoire de Chimie Physique et Chimie Minérale, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'observatoire, 75006 Paris, France.
authors.forename: René
authors.initials: R
authors.lastname: Céolin
authors.affiliation: Laboratoire de Chimie Physique et Chimie Minérale, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'observatoire, 75006 Paris, France.
authors.forename: Léon Ter
authors.initials: LT
authors.lastname: Minassian
authors.affiliation: Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, Diagonal 647, 08028 Barcelona, Catalunya, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Barrio
authors.affiliation: Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, Diagonal 647, 08028 Barcelona, Catalunya, Spain.
authors.forename: Nestor
authors.initials: N
authors.lastname: Veglio
authors.affiliation: Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, Diagonal 647, 08028 Barcelona, Catalunya, Spain.
authors.forename: Josep-Lluis
authors.initials: JL
authors.lastname: Tamarit
authors.affiliation: Laboratoire de Chimie du Solide et Inorganique Moléculaire, UMR CNRS 6511, Université de Rennes I, Avenue du Général Leclerc, 35042 Rennes Cedex, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Louër
authors.affiliation: Laboratoire de Chimie Physique et Chimie Minérale, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'observatoire, 75006 Paris, France. Electronic address: ivo.rietveld@parisdescartes.fr.
authors.forename: Ivo B
authors.initials: IB
authors.lastname: Rietveld
mesh_terms: D004355:Drug Stability; D044367:Phase Transition; D010889:Piracetam / Q000737:chemistry*; D011312:Pressure; D013696:Temperature
chemical_list: D010889:Piracetam
keywords: Crystal polymorphism; Phase diagram; Phase transition; Physical stability; Preformulation; Solid state