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过程工程学报 ›› 2020, Vol. 20 ›› Issue (2): 213-221.DOI: 10.12034/j.issn.1009-606X.219206

• 过程与工艺 • 上一篇    下一篇

二丁酰环磷腺苷钠在水-丙酮混合溶剂中溶解度的测定与关联

魏兵惠1， 王九成2， 高 峰1*   

  1. 1. 华东理工大学药学院，上海 200237 2. 西安力邦制药有限公司，陕西 西安 710075
  • 收稿日期:2019-05-15 修回日期:2019-06-24 出版日期:2020-02-22 发布日期:2020-02-19
  • 通讯作者: 高峰 fgao@ecust.edu.cn
  • 基金资助:
    上海市自然科学基金

Measurement and correlation of solubility of bucladesine sodium in water-acetone mixed solvent

Binghui WEI1, Jiucheng WANG2, Feng GAO1*   

  1. 1. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China 2. Xi?an Libang Pharmaceutical Co., Ltd., Xi?an, Shaanxi 710075, China
  • Received:2019-05-15 Revised:2019-06-24 Online:2020-02-22 Published:2020-02-19
  • Contact: Feng Feng GaoGao fgao@ecust.edu.cn
  • Supported by:
    Shanghai Municipal Natural Science Foundation

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摘要： 通过高效液相色谱法(HPLC)测定了二丁酰环磷腺苷钠在水?丙酮混合溶剂中的溶解度，利用修正的Apelblat模型、λh模型和C/R?K模型关联溶解度数据并计算模型参数，计算了二丁酰环磷腺苷钠在水?丙酮混合溶剂中溶解过程的热力学参数，测定了二丁酰环磷腺苷钠与2种相关杂质的溶解度。结果表明，在278.15?298.15 K温度范围内，二丁酰环磷腺苷钠的溶解度随温度升高而增大，随丙酮摩尔分数增加先增大后减小，可能是共溶剂现象所致。丙酮摩尔分数为0.4220时，二丁酰环磷腺苷钠的溶解度最大。实验数据与模型拟合良好。标准溶解焓大于零、标准溶解吉布斯自由能小于零，表明该溶解过程为自发进行的吸热过程。丙酮摩尔分数为0.7110～0.8538时，二丁酰环磷腺苷钠、杂质N6-单丁酰基腺苷-3',5'-环磷酸酯钠和2?-O-单丁酰基腺苷-3',5'-环磷酸酯钠的溶解度有显著差异，为其结晶分离提供了理论依据。

关键词: 二丁酰环磷腺苷钠, 溶解度, 模型关联, 热力学参数, 杂质

Abstract: The molar solubility of bucladesine sodium in water?acetone mixed solvent was measured by High Performance Liquid Chromatography (HPLC) at atmospheric pressure and temperature of 278.15?298.15 K. Moreover, the modified Apelblat, λh and C/R?K models were used to correlate and analyze the experimental solubility data of bucladesine sodium. The thermodynamic properties of bucladesine sodium dissolution process, including the changes of enthalpy, entropy and Gibbs free energy, were calculated based on modified Apelblat model. Furthermore, the molar solubility difference between bucladesine sodium and two related impurities (sodium N6-butyryladenosine-3',5'-cyclic phosphate and sodium 2′-O-butyryladenosine-3',5'-cyclic phosphate) in mixed solvent was determined as the molar fraction of acetone was 0.7110～1.0000. The results showed that the molar solubility of bucladesine sodium in mixed solvent increased as the temperature increased. With increasing molar fraction of acetone, the molar solubility of bucladesine sodium increased to the maximum and then decreased, which could be explained by cosolvent phenomenon. When the molar fraction of acetone was 0.4220, the molar solubility of bucladesine sodium was the largest. It was found that the three models showed good correlation effect with low relative average deviation (RAD) and root-mean-square deviation (RMSD) values which demonstrated that the correlated values were in good agreement with the experimental values throughout the entire range of temperature and tested molar fraction of acetone. The change of enthalpy of dissolution process was positive while the change of Gibbs free energy was negative, which indicated that the dissolution process of bucladesine sodium in mixed solvent was a spontaneous endothermic process. The molar solubilities of bucladesine sodium and two related impurities increased with increasing temperature and decreased with increasing molar fraction of acetone, but there was a significant difference between the molar solubility of bucladesine sodium and two related impurities as the molar fraction of acetone increased from 0.7110 to 0.8538. The above solubility characteristics of bucladesine sodium and two related impurities could be used as the basic data for further study in bucladesine sodium crystallization process.

Key words: bucladesine sodium, solubility, correlation, thermodynamic parameter, impurity