Investigation on thermodynamics and kinetics of puerarin sodium chelate
10.16438/j.0513-4870.2023-1340
- VernacularTitle:葛根素钠螯合物形成的热力学动力学机制研究
- Author:
Wei JIANG
1
;
Jun-xiao ZHU
2
;
Hui CHEN
3
;
Jing-wen ZHANG
3
;
Jian-jun ZHANG
3
;
Yuan GAO
2
;
Shuai QIAN
2
;
Yuan-feng WEI
2
Author Information
1. Zhejiang Zhenyuan Pharmaceutical Co., Ltd., Shaoxing 312000, China
2. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
3. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
- Publication Type:Research Article
- Keywords:
puerarin;
sodium chelate;
thermodynamics;
inetics;
solubility
- From:
Acta Pharmaceutica Sinica
2024;59(9):2648-2658
- CountryChina
- Language:Chinese
-
Abstract:
Tablets represent the most widely used oral solid dosage form in the pharmaceutical industry. Puerarin monohydrate (PUEM), a solid form of the natural antihypertensive drug puerarin, is commercially available. However, the low solubility of PUEM poses a significant challenge for the development of its tablet dosage form. In this study, we successfully prepared the sodium chelates of puerarin (PUE-Na·7H2O) using reactive crystallization techniques. The crystal structure of PUE-Na·7H2O was analyzed using single crystal technology, which revealed the structural characteristics of its metal chelate. Our thermodynamic studies demonstrated that the formation of PUE-Na·7H2O involved the simultaneous deprotonation of PUE and the chelation of PUE- and Na+. This reaction process was spontaneous and exothermic (ΔG < 0, ΔH < 0), and reducing the temperature facilitated the formation of the chelate. Nucleation kinetics studies revealed that chelate molecules were more likely to nucleate and crystallize under low temperature, high concentration, and high rotational speed conditions. Compared to commercially available PUEM, PUE-Na·7H2O showed significantly improved water solubility, with a 33.5-fold increase in solubility and a 37.6-fold decrease in intrinsic dissolution rate. Our study identified drug-sodium chelation as an effective means for improving drug solubility and elucidated the mechanisms governing its formation kinetics and thermodynamics. These findings could provide new solutions for related product development and tremendous commercial opportunities.
