(Solid + liquid) phase diagram for (indomethacin + nicotinamide)-methanol or methanol/ethyl acetate mixture and solubility behavior of 1:1 (indomethacin + nicotinamide) co-crystal at T = (298.15 and 313.15) K. (June 2015)

• Record Type: Journal Article
• Authors: Sun, Xiaowei; Yin, Qiuxiang; Ding, Suping; Shen, Zhiming; Bao, Ying; Gong, Junbo; Hou, Baohong; Hao, Hongxun; Wang, Yongli; Wang, Jingkang; Xie, Chuang
• Is Part Of: Journal of chemical thermodynamics. Volume 85(2015:Jun.)
• Page Start: 171
• Page End: 177
• Publication Date: 2015-06
• Subjects: Indomethacin -- Co-crystal -- Solvate -- Solubility -- Phase diagram; Thermodynamics -- Periodicals; Thermochemistry -- Periodicals; Thermodynamique -- Périodiques; Thermochimie -- Périodiques; Thermochemistry; Thermodynamics; Periodicals; 541.369
• DOI: 10.1016/j.jct.2015.01.015
• Languages: English
• ISSNs: 0021-9614

Abstract

Graphical abstract: Highlights: Ternary phase diagrams of (IMC + NCT)-methanol or methanol/ethyl acetate mixture at T = (298.15 and 313.15) K were measured. The effects of temperature and introduced ethyl acetate on solid phase stability were discussed. Solubility of (IMC + NCT) cocrystals was first correlated using a model considering solubility product and complexation. Solubility of (IMC + NCT) cocrystals as a function of co-former concentration was evaluated. Abstract: (Solid + liquid) equilibrium data for indomethacin (IMC) and nicotinamide (NCT) in both methanol (MeOH) and methanol/ethyl acetate (EA) mixture were determined using a static method at T = (298.15 and 313.15) K under atmospheric pressure. The 1:1 (IMC + NCT) co-crystal and IMC·MeOH were found in both systems under conditions investigated. The solubility of the 1:1 (IMC + NCT) co-crystal was correlated using a mathematical model consisting of both solubility product and a complexation process. Solubility of (IMC + NCT) co-crystals as a function of co-former (NCT) concentration was evaluated. It was found that temperature has a significant effect on the formation of methanol solvate in the systems investigated. Solvate formation could be suppressed either by increasing temperature or using solvent mixtures. Additionally, the solvent mixture could level out the solubility differences between IMC and NCT, resulting in larger and more symmetric regions for the (IMC + NCT) co-crystal, which would be helpful to the development of the co-crystallization process for the 1:1 (IMC + NCT) co-crystal.