title: [Thermodynamics of drug polymorphism: domains and stability hierarchy by pressure temperature diagram. Application to the tetramorphism of fananserine].
abstract: In this communication, an application of classical thermodynamics to crystalline solid state polymorphism is shown to allow stability p, T domains and stability hierarchy among crystalline phases of a polymorph to be defined by constructing the unary p, T phase diagram. The three topological rules upon which this construction is founded are presented; the first one is a straight consequence of the least vapour pressure criterion by Ostwald. Calculation of triple point co-ordinates and of two-phase equilibrium curves is based upon using both thermodynamic and crystallographic data obtained at ordinary pressure. Clapeyron equation allows the slopes of the straight lines representing equilibria between condensed phases to be calculated and, hence, triple points situated at high or  negative  pressure to be determined. On the other hand, the hierarchy among the thermodynamic stability degrees of the crystalline varieties may be inferred from the location of the sublimation curves, by merely acknowledging inequalities among vapour pressures at each temperature on the whole T-range. These building-up processes are pointed out by outlining the achievement of a phase diagram related to the tetramorphism of fananserine, an anxiolytic drug. Three out four crystalline forms, namely phases II, III and IV, possess their own stability domain, although those belonging to phases II and III are limited at high pressure by that of phase IV. Conversely, phase I is overall metastable and exhibits a whole monotropic behaviour.
authors.affiliation: Laboratoire de Chimie Physique et de Chimie Minérale, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes - Paris V, 4, Avenue de l'Observatoire, F75006 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Toscani
mesh_terms: D014151:Anti-Anxiety Agents / Q000737:chemistry*; D003499:Cyclic S-Oxides / Q000737:chemistry*; D004355:Drug Stability; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry*; D011312:Pressure; D013816:Thermodynamics
chemical_list: D014151:Anti-Anxiety Agents; D003499:Cyclic S-Oxides; D009281:Naphthalenes; C070475:fananserin
vernacular_title: Thermodynamique du polymorphisme des médicaments: domaines et hiérarchies de stabilité des phases par le diagramme pression-température (p,T). Application au tétramorphisme de la fanansérine.