盐酸苯达莫司汀的热稳定性与晶型对比研究

Comparative Study of Thermal Stability and Crystal form of Bendamustine Hydrochloride

目的:对盐酸苯达莫司汀晶型Ⅰ、晶型Ⅱ、晶型D三种晶型作稳定性对比研究。方法:通过差示扫描量热仪(DSC)和热重分析仪(TGA)分析盐酸苯达莫司汀的热稳定性,并做晶型稳定性研究,分析其稳定性;利用X射线粉末衍射仪(XRD)测定盐酸苯达莫司汀的多晶型结构。结果:盐酸苯达莫司汀是存在多晶型的。故筛选出两种较优晶型Ⅰ、D与晶型Ⅱ进行对比研究,其中晶型Ⅰ(无结晶水)、晶型Ⅱ(一分子结晶水)熔点分别为158.9℃和170.3℃;晶型D(一分子结晶水)则在158.0℃和170.8℃出现两个熔点;晶型Ⅰ、晶型Ⅱ、晶型D通过X射线粉末衍射仪(XRD)的检测,说明其分属于不同晶型。结论:通过稳定性对比研究,可以说明晶型Ⅱ的稳定性与其他两种专利晶型稳定性相当,且在医药生产中晶型Ⅱ更适合仿制药的研发生产。

Objective:A comparative study on the stability of bendamustine hydrochloride form Ⅰ,form Ⅱ and form D was conducted.Methods:The thermal stability and crystal stability of bendamustine hydrochloride were analyzed by using differential scanning calorimeter(DSC)and thermogravimetric analyzer(TGA).The polymorphic structure of bendamustine hydrochloride was determined by X-ray powder diffractometer(XRD).Results:The results showed that bendamustine hydrochloride existed as polymorphic forms.Therefore,forms Ⅰ and Form D were selected for comparing with form Ⅱ.The melting points of form Ⅰ(no crystal water)and form Ⅱ(one molecule of crystalline water)were 158.9℃and 170.3℃,respectively,while crystalline form D(one Molecular crystallization water)has two melting points at 158.0℃and 170.8℃.Moreover,form Ⅰ,form Ⅱ and form D were detected by X-ray powder diffractometer(XRD),indicating that they belonged to different crystal forms.Conclusion:According to the comparison of stability,it showed that the stability of form Ⅱ was similar to that of other two patented forms,and form Ⅱ was more suitable for the development and production of generic drugs in pharmaceutical production.