摘要
目的:磷酸苯丙哌林多晶型的研究,为磷酸苯丙哌林原料药生产工艺的改进及质量的提升提供技术支持。方法:采用不同溶剂重结晶获得3种不同于原料药晶型的磷酸苯丙哌林。采用粉末X射线衍射仪、电镜扫描、差示扫描量热及热重分析、熔点测定、红外吸收光谱表征了4种磷酸苯丙哌林晶型,并使用高效液相色谱法测定了4种晶型在不同pH缓冲液中的平衡溶解度。结果:重结晶的磷酸苯丙哌林具有不同的X射线特征峰,电镜外观形貌也存在明显差异,且重结晶获得的3种晶型的平衡溶解度均高于原料药晶型。结论:可通过对磷酸苯丙哌林原料药结晶溶剂的调整,获得表观溶解度更好的晶型。
Objective:The polymorphs research of benproperine phosphate provides technical support for improvement of API quality and production process.Methods:Three different crystal forms of benproperine phosphate which were diffrent from API crystal form were obtained by recrystallization in different solvents.Four crystal forms of benproperine phosphate were characterized by powder X-ray diffractometer,scanning electron microscope,differential scanning calorimetry and thermogravimetric analysis,melting point determination and infrared absorption spectrum,and their equilibrium solubility in different pH buffers was determined.Results:Four different crystal forms of benproperine phosphate had different X-ray characteristic peaks,and the appearance and morphology of electron microscope are also obviously different.The equilibrium solubility of three new crystal forms in three kinds of buffers was significantly improved.Conclusion:By adjusting the crystallization solvent of benproperine phosphate,the crystal forms with better equilibrium solubility can be obtained.
作者
徐桂连
董斌
韩春晖
郝爱鱼
XU Gui-lian;DONG Bin;HAN Chun-hui;HAO Ai-yu(Dalian institute for Drug Control,Liaoning Dalian 116021,China)
出处
《中国药物评价》
2023年第6期489-493,共5页
Chinese Journal of Drug Evaluation
基金
2021年大连市青年科技之星项目(磷酸苯丙哌林(咳快好)生产工艺风险管控关键评价技术研究,课题编号:2021RQ032)。
关键词
磷酸苯丙哌林
多晶型
表征
平衡溶解度
Benproperine phosphate
Polymorphs
Characterization
Equilibrium solubility
