Characterization of the conglomerate form of acetyl-dl-leucine by thermal analysis and solubility measurements

Nicolas Estime (1) , Richard Pena (2) , Sébastien Teychené (1) , Jean Marie Autret , Béatrice Biscans (1)

1 LGC - Laboratoire de Génie Chimique
2 Département Physico-Chimie (Castres, France)

Starting from a mixture of enantiomers in solution, crystallization can generate different types of crystals. In order to determine which type of crystal is obtained in the case of acetylleucine, an active pharmaceutical ingredient (API), analytical methods have been used to partially elucidate the binary and ternary phase diagrams of the system composed of the two enantiomers and water.The melting temperature phase diagram of this compound has been obtained by using differential scanning calorimetry (DSC) analyzes. The results show that it is characteristic of a conglomerate. This mode of crystallization has also been confirmed by X-ray powder diffraction analysis. Solubility measurements of enantiomerical mixtures in water enabled the determination of the ternary diagram of solubility. The empiric Meyerhoffer double solubility rule has been modified, due to the characterization of interactions between enantiomers.

Mots clés: A1. Conglomerate; A1. Phase diagram; A1. Racemic; A2. Crystallization; B1. Acetylleucine

Domaines: Cristallographie; Génie chimique; Dynamique des Fluides [physics.flu-dyn]; Sciences pharmaceutiques; Thermique [physics.class-ph]

Nicolas Estime, Richard Pena, Sébastien Teychené, Jean Marie Autret, Béatrice Biscans. Characterization of the conglomerate form of acetyl-dl-leucine by thermal analysis and solubility measurements. Journal of Crystal Growth, 2012, vol. 342 (n° 1), pp. 28-33. ⟨10.1016/J.JCRYSGRO.2011.03.023⟩. ⟨hal-03536619⟩