Thermodynamic studies of naringenin-isonicotinamide cocrystals
10.16438/j.0513-4870.2016-1155
- VernacularTitle:柚皮素-异烟酰胺共晶形成热力学的研究
- Author:
Shu-jun LIANG
1
;
Sheng-yan ZHOU
2
;
Si-tong YANG
2
;
Dian-rong XIA
1
;
Yuan-feng WEI
2
;
Yuan GAO
2
;
Shuai QIAN
2
;
Jian-jun ZHANG
1
Author Information
1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
2. Department of Traditional Chinese Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
naringenin;
isonicotinamide;
cocrystal;
solution complexation;
thermodynamics;
ternary phase diagram
- From:
Acta Pharmaceutica Sinica
2017;52(4):625-633
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this study was to investigate the thermodynamics of naringenin (NAR)-isonicotinamide (INT) cocrystal (stoichiometric ratio, 1∶2) formed in different solvents. The dissolution behavior of cocrystal was explored in the water. Solubility of NAR-INT cocrystals under various temperatures were measured, followed by fitting the complexation model to calculate the thermodynamic parameters solubility products (Ksp), complexation constants (K12) and Gibbs energy change (ΔG) of cocrystal during formation progress. Ternary phase diagrams (TPDs) of the NAR-INT-solvent systems under various temperatures were plotted. Based on the non-linear simulation, 1∶2 complexation model was well fitted to the NAR-INT cocrystal formation in ethanol, isopropanol and ethyl acetate, while no complexation model was more suitable for that in methanol. The cocrystallization reaction was exothermic and spontaneous (ΔG < 0, ΔH < 0, ΔS < 0). Ksp increased while K12 decreased when increasing temperature, suggesting that the two components could cocrystallize more easily at the lower temperature. In comparison to TPDs in other solvents, the area of homogeneous liquid phase in ethyl acetate was the smallest, indicating the easiest formation of NAR-INT cocrystal in ethyl acetate. The current study provides a theoretical foundation for preparation and optimization of scale-up NAR-INT cocrystals.
