title: Rimonabant dimorphism and its pressure-temperature phase diagram: a delicate case of overall monotropic behavior.
abstract: Crystalline polymorphism occurs frequently in the solid state of active pharmaceutical ingredients, and this is problematic for the development of a suitable dose form. Rimonabant, an active pharmaceutical ingredient developed by Sanofi and discontinued because of side effects, exhibits dimorphism; both solid forms have nearly the same melting temperatures, melting enthalpies, and specific volumes. Although the problem may well be academic from an industrial point of view, the present case demonstrates the usefulness of constructing pressure-temperature phase diagrams by direct measurement as well as by topological approach. The system is overall monotropic and form II is the more stable solid form. Interestingly, the more stable form does not possess any hydrogen bonds, whereas the less stable one does.
authors.affiliation: Sanofi R&D, Lead Generation and Compound Realization/Analytical Sciences/Solid State Group, Vitry sur Seine 94400, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Perrin
authors.forename: Michel
authors.initials: M
authors.lastname: Bauer
authors.forename: Maria
authors.initials: M
authors.lastname: Barrio
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: D063387:Cannabinoid Receptor Antagonists / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D044367:Phase Transition; D010880:Piperidines / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D000077285:Rimonabant; D055548:Vapor Pressure
chemical_list: D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant