CIESC Journal ›› 2019, Vol. 70 ›› Issue (11): 4153-4161.DOI: 10.11949/0438-1157.20190712

• Thermodynamics • Previous Articles     Next Articles

Determination of solubility and ternary phase diagram of lamotrigine-phthalimide pharmaceutical cocrystal in pure solvent

Jinyan ZHANG1(),Wenjie KUANG1,Shaochang JI2,Xiaoxue CAO1,Anping LIAO1,Ping LAN1()   

  1. 1. Guangxi Key Laboratory for Polysaccharide Materials and Modification, Key Laboratory of Chemical and Biological Transformation Process of Guangxi Higher Education Institutes, College of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning 530006, Guangxi, China
    2. Guangxi Tobacco Monopoly Bureau, Nanning 530006, Guangxi, China
  • Received:2019-06-24 Revised:2019-08-15 Online:2019-11-05 Published:2019-11-05
  • Contact: Ping LAN

拉莫三嗪-邻苯二甲酰亚胺药物共晶在有机溶剂中溶解度及三元相图测定

张金彦1(),匡雯婕1,吉绍长2,曹小雪1,廖安平1,蓝平1()   

  1. 1. 广西民族大学化学化工学院,广西多糖材料与改性重点实验室,广西高校化学与生物转化过程新技术重点实验室,广西 南宁530006
    2. 广西烟草专卖局,广西 南宁 530006
  • 通讯作者: 蓝平
  • 作者简介:张金彦(1984—),女,博士,副教授,zjy_03@126.com
  • 基金资助:
    国家自然科学基金项目(21606056);广西自然科学基金项目(2017GXNSFAA198091);广西生物多糖分离纯化及改性研究平台建设项目(桂科ZY18076005);广西民族大学相思湖创新团队项目(2016);广西民族大学研究生教育创新计划项目(gxun-chxps201817)

Abstract:

The solubilities of lamotrigine in n-propanol, isopropanol, n-butanol, isobutanol, ethyl propionate, methyl acetate were determined by the static method at a temperature range of 283.15 K to 323.15 K and correlated by Apelblat equation and λh equation. The results showed that the solubility of lamotrigine increased with the increase of temperature, and the solubility of n-butyl alcohol > n-propyl alcohol > isobutanol > isopropanol, methyl acetate > ethyl propionate. Apelblat equation had better fitting effect, which can be used to predict the thermodynamic behavior of lamotrigine monomer. On this basis, the lamotrigine-phthalimide cocrystal was presented and the ternary phase diagram of lamotrigine- phthalimide - solvent was established in isobutanol and ethyl propionate at 298.15 K and 303.15 K.The results showed that with the increase of temperature, the stability region for the pure lamotrigine - phthalimide cocrystal was increased, and the ternary phase diagram was symmetrical in isobutanol, which was conducived to cocrystal formed.

Key words: lamotrigine, phthalimide, pharmaceutical cocrystal, thermodynamics, phase equilibria, solubility

摘要:

采用静态法测定了拉莫三嗪在正丙醇、异丙醇、正丁醇、异丁醇、丙酸乙酯、乙酸甲酯6种溶剂中的热力学行为,并采用Apelblat方程和λh方程进行了关联,其结果表明拉莫三嗪的溶解度随着温度的升高而升高,溶解行为由低到高为正丁醇>正丙醇>异丁醇>异丙醇,乙酸甲酯>丙酸乙酯,应用的方程拟合度较好,可用于单体拉莫三嗪热力学行为的预测。在此基础上,采用溶液法制备拉莫三嗪-邻苯二甲酰亚胺共晶,在298.15、303.15 K时,建立了共晶体在异丁醇、丙酸乙酯溶剂中的三元相图,结果表明同一溶剂体系内,随着温度的升高,拉莫三嗪-邻苯二甲酰亚胺共晶区域增大,有利于共晶的形成。同一温度下,拉莫三嗪-邻苯二甲酰亚胺共晶在异丁醇体系的对称性优于丙酸乙酯体系,表明拉莫三嗪-邻苯二甲酰亚胺共晶更易于在异丁醇体系中获得。

关键词: 拉莫三嗪, 邻苯二甲酰亚胺, 药物共晶, 热力学, 相平衡, 溶解性

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