title: Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.
abstract: Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases.
authors.affiliation: EAD Physico-chimie Industrielle du Médicament (EA4066), Faculté de Pharmacie, Université Paris Descartes, 4, Avenue de l'Observatoire, 75006 Paris, France; Etablissement Pharmaceutique de l'Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, 7, rue du Fer à Moulin, 75005 Paris, France; Laboratoire de chimie analytique, Faculté de Pharmacie, rue Ibn Sina, 5000 Monastir, Tunisia.
authors.forename: Inès
authors.initials: I
authors.lastname: Gana
authors.forename: Maria
authors.initials: M
authors.lastname: Barrio
authors.forename: Bernard
authors.initials: B
authors.lastname: Do
authors.forename: Josep-Lluís
authors.initials: JL
authors.lastname: Tamarit
authors.forename: René
authors.initials: R
authors.lastname: Céolin
authors.forename: Ivo B
authors.initials: IB
authors.lastname: Rietveld
mesh_terms: D001566:Benzocaine / Q000737:chemistry* / Q000493:pharmacokinetics; D003460:Crystallization; D011312:Pressure; D044366:Transition Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D001566:Benzocaine
keywords: Phase diagram; Physical stability; Polymorphism; Pressure; Thermodynamics; X-ray powder diffraction