Journées d'Étude des Équilibres entre Phases

J. Phys. IV France 11 (2001) Pr10-93-Pr10-97
DOI: 10.1051/jp4:20011012

Polymorphism and hydration of zopiclone : Determination of crystal structures, and thermodynamic studies as a function of temperature and water vapor pressure

J. Giovannini^{1, 2}, R. Céolin³, M.-A. Perrin¹, S. Toscani³, D. Louër² and F. Leveiller<sup>1

1</sup>  AVENTIS PHARMA, Global Pharmaceutical Development, Pharmaceutical Sciences, Material and Drug Delivery Design, CRV1, 13 quai Jules Guesde, BP. 14, 94403 Vitry-sur-Seine cedex, France
²  Institut de Chimie, Laboratoire de Chimie du Solide et Inorganique Moléculaire, UMR 6511 du CNRS, Cristallographie des Poudres et Réactivité des Solides, Université de Rennes I, avenue du Général Leclerc, 35042 Rennes cedex, France
³  Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Physique, Université Paris V, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France

Abstract
Racemic Zopiclone crystallises as a dihydrate (DH) or as a conglomerate (A). Upon heating, DH dehydrates to an anhydrous racemate (B) which transforms into the 1:l mixture of enantiomers (A). It can be inferred from crystallographic and thermodynamic data that the anhydrous racemate is metastable with respect to the 1:l mixture of enantiomers (A) whatever the water vapour pressure and the temperature. Thus, the B → A transition appears to occur monotropically.

© EDP Sciences 2001