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J Zhejiang Univ (Med Sci)  2017, Vol. 46 Issue (2): 153-159    DOI: 10.3785/j.issn.1008-9292.2017.04.06
    
Characterization and stability of S (-) pantoprazole sodium hydrates
CHEN Bei1(),ZHANG Libo2,LI Hong2,TANG Guping3,*(),HU Xiurong3,*()
1. School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2. Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co., Ltd, Hangzhou 310011, China
3. Department of Chemistry, Zhejiang University, Hangzhou 310028, China
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Abstract  

Objective: To study the characteristics and stability of new S(-) pantoprazole sodium hydrates. Methods: The X-ray single crystal diffractometer (SXRD), X-ray powder diffractometer (PXRD), thermogravimetric analysis (TG) and infrared spectrometry (IR) were used to characterize S(-) pantoprazole sodium hydrates. The stability of the hydrates was evaluated by high temperature test,affecting factors test and accelerated test. Results: The crystalline water in S(-) pantoprazole sodium hydrates were very easy to lose and obtain, but crystal structure was not changed significantly. The transition from S(-) pantoprazole sodium trihydrate to S(-) pantoprazole sodium hemipentahydrate occurred at approximately 40 ℃ and reversible transitions from hemipentahydrate to trihydrate occurred at high humidity. Two hydrates had no significant difference in accelerated test. Conclusion: The crystal structure of the two hydrates are almost the same, hemipentahydrate is more stable than trihydrates at high temperature or at exposure to light(at 4500 ± 500 lx).



Key wordsBenzimidazoles/analysis      Omeprazole/analysis      Sodium      Drug stability      X-ray diffraction      Water      Lens, cystalline/anatomy & histology     
Received: 02 November 2016      Published: 31 October 2017
Corresponding Authors: TANG Guping,HU Xiurong     E-mail: 87560024@qq.com;tangguping@zju.edu.cn;huxiurong@zju.edu.cn
Cite this article:

CHEN Bei,ZHANG Libo,LI Hong,TANG Guping,HU Xiurong. Characterization and stability of S (-) pantoprazole sodium hydrates. J Zhejiang Univ (Med Sci), 2017, 46(2): 153-159.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2017.04.06     OR     http://www.zjujournals.com/xueshu/med/Y2017/V46/I2/153


新型左旋泮托拉唑钠水合物晶型结构及稳定性研究

目的:研究新型左旋泮托拉唑钠水合物晶型——左旋泮托拉唑钠二点五水合物晶型的结构和稳定性。方法:采用X射线单晶衍射、X射线粉末衍射、热重分析、红外光谱等多种分析方法,对左旋泮托拉唑钠水合物晶型进行结构表征;并通过热处理实验、影响因素试验及加速试验对左旋泮托拉唑钠水合物的稳定性进行研究。结果:在高湿条件下,左旋泮托拉唑钠二点五水合物极易吸水,转变成左旋泮托拉唑钠三水合物;左旋泮托拉唑钠三水合物在40 ℃热处理条件下极易转变成左旋泮托拉唑钠二点五水合物,但晶型的空间结构不发生改变,即左旋泮托拉唑钠二点五水合物和三水合物具有相同的晶体结构,只是其中结晶水含量有差别;加速试验条件下两者变化趋势基本一致。结论:左旋泮托拉唑钠二点五水与左旋泮托拉唑钠三水合物合物具有相同的晶体结构,但二点五水合物在40 ℃高温及光照(4500±500)lx条件下稳定性优于三水合物。


关键词: 苯咪唑类/分析,  奥美拉唑/分析,  钠,  药物稳定性,  X线衍射,  水,  晶体/解剖学和组织学 
Fig 1 Chemical structure of S(-) pantoprazole sodium hemipentahydrate
Fig 2 Comparison of IR diagram for S(-) pantoprazole sodium hemipentahydrate and S(-) pantoprazole sodium trihydrate a-S(-) pantoprazole sodium trihydrate; b-S(-) pantoprazole sodium hemipentahydrate
Fig 3 Structure of S(-) pantoprazole sodium trihydrate
Fig 4 Packing of S(-) pantoprazole sodium trihydrate
Fig 5 Comparison of X-ray powder diffractograms for S(-) pantoprazole sodium hemipentahydrate and S(-) pantoprazole sodium trihydratea-S(-) pantoprazole sodium trihydrate; b-S(-) pantoprazole sodium hemipentahydrate
Fig 6 Comparison of TG diagram for S(-) pantoprazole sodium hemipentahydrate and S(-) pantoprazole sodium trihydratea-S(-) pantoprazole sodium trihydrate; b-S(-) pantoprazole sodium hemipentahydrate
温度(℃) 加热时间(min) 二点五水合物 三水合物
水分(%) 特征衍射峰 水分(%) 特征衍射峰
45 15 10.0  无变化 10.1  略宽化
45 90 8.5  宽化 8.4  宽化
50 120 6.2  宽化,且已有部分无定型产生 6.1  宽化,且已有部分无定型产生
50 120 1.9  晶型变为无定型 1.8  晶型变为无定型
65 30
Tab 1 The stability of the hemipentahydrate and trihydrate by heat treatment
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