Gibbs Formation Energy of a Cocrystal that Dissociates into a Hydrate

• Published in: Crystal growth & design Vol. 22; no. 8; pp. 4777 - 4786
• Main Authors: Khope, Swapnil, Pal, Sharmistha
• Format: Journal Article
• Language: English
• Published: American Chemical Society 03.08.2022
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.2c00206

The Gibbs energy of formation, ΔG f, of a cocrystal is a fundamental property to determine its thermodynamic stability. One of the methods to determine ΔG f is from the eutectic composition of the components of the cocrystal in a given solvent. However, conventional methods to determine the ΔG f of a cocrystal from the eutectic composition in a given solvent are indicated to be valid when it dissociates into an unsolvated (or anhydrous) form of the components in that solvent. This article explores the condition when the ΔG f of a cocrystal may be calculated from its eutectic composition in a solvent where the thermodynamically stable form of one of the components is a hydrate. The theophylline–nicotinamide cocrystal, which dissociates into theophylline hydrate and nicotinamide in water, is used as the model cocrystal in this study. The calculated ΔG f values of the cocrystal from water are compared with those obtained from the eutectic composition of the cocrystal in nonsolvate forming solvents, namely, ethyl acetate and 2-propanol. The implication of the study in pharmaceutical development of cocrystal is discussed.