泮托拉唑钠单水合物与倍半水合物的晶型与稳定性差异研究  

Difference of crystal forms and stability between pantoprazole sodium monohydrate and sesquihydrate

作　　者：邱珲 杨庆云[1] 童元峰[1] 吴松[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中国新药杂志》2015年第8期869-874,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2013ZX09402103)

摘　　要：目的:研究泮托拉唑钠单水合物和倍半水合物的晶型及稳定性差异。方法:采用差示扫描量热法和X-射线粉末衍射等多种分析方法,对两种结晶水合物进行表征;通过吸湿性试验、影响因素试验及加速试验,对两种水合物的稳定性进行对比研究。结果:表征晶型的分析测定参数存在差异;单水合物较倍半水合物更具吸湿性;在影响因素试验条件下,单水合物有关物质检测中均有未知杂质产生,在高温、高湿条件下颜色发生变化,高湿条件下含水量增加,倍半水合物无显著变化;两种结晶水合物在加速实验条件下放置6个月基本无变化。结论:两种结晶水合物的晶型不同;倍半水合物在光照、高温和高湿条件下均较单水合物稳定;将单水合物密封包装后置于凉暗处保存,可有效隔绝湿度等外界条件对样品的影响,保证样品的稳定性。Objective ： To estimate the difference of crystal form and stability between pantoprazole sodium monohydrate and sesquihydrate. Methods： The differential scanning calorimetry （DSC） , thermogravimetric analy- sis （TGA）, melting point determination, X-ray powder diffraction （XRPD） and infrared spectra were used to per- form detailed characterization of pantoparzole sodium crystal forms. The stability of the two crystalline hydrates were evaluated by lead wet test, stress test and accelerated test. Results： Differences between the two crystalline hydrates can be found on the TGA, DSC, melting point, XRPD and IR, in stress test and lead wet test. Monohydrate had a certain change under the condition of high temperature, high humidity and strong illumination test; both two hydrates had no significant stability change in accelerated test. Conclusion： The crystal form, hygroscopicity and stability of the two hydrates are different. Monohydrate is considerable hygroscopic in comparison with sesquihydrate; and under the condition of stress test, sesquihydrate is more stable. By the means of sealed packaging and storing in cool and dark, it can effectively protect the sample of monohydrate from the influence of external conditions such as humidity, thus guaranteeing the stability of the sample.

关 键 词：泮托拉唑钠 单水合物 倍半水合物 晶型研究 稳定性研究 

分 类 号：R975.6[医药卫生—药品]