目的 制备艾司奥美拉唑钠肠溶固体分散体片(E-EsSDT),以改善艾司奥美拉唑钠(Es)的引湿性、热不稳定性以及口服遇酸降解的问题。方法 基于质量源于设计理念,运用鱼骨分析图筛选E-EsSDT的关键质量属性,并采用单因素考察法、Plackett-Burman设计及Box-Behnken设计对E-EsSDT进行优化及表征分析。结果 最佳处方为水与乙酸羟丙基甲基纤维素琥珀酸酯-LG(AS-LG)比例为3∶22、Es与AS-LG比例为1:3.5、剪切间断时间为44 s。稳定性试验结果表明,E-EsSDT的Es含量、吸湿增重、耐酸力均符合规定;表征分析表明,Es以无定型形式存在于固体分散体中。结论 E-EsSDT的制备同时解决了Es引湿性、热不稳定性以及口服遇酸降解的问题。
Abstract
OBJECTIVE To prepare esomeprazole sodium(Es) enteric solid dispersion tablets (E-ESSDT), improve the wettability, thermal instability and oral acid degradation of esomeprazole sodium. METHODS Based on the concept of quality derived from design, fishbone analysis diagram was used to screen the key quality attributes of E-EsSDT, and single-factor investigation method, Plackett-Burman design and Box-Behnken design were used to optimize and characterize the E-EsSDT. RESULTS The optimal formula was that the ratio of water to hydoxpropylmethylcellulose succinate-LG(AS-LG) was 3∶22, the ratio of Es to AS-LG was 1∶3.5, and the shear break time was 44 seconds.The stability test results showed that the Es content, moisture absorption and weight gain and acid resistance of E-EsSDT were all in accordance with the regulations.Characterization analysis showed that Es existed in amorphous form in solid dispersion. CONCLUSION The preparation of E-EsSDT solves the problems of moisture absorption, thermal instability and acid degradation of Es by oral administration.
关键词
艾司奥美拉唑钠 /
固体分散体 /
质量源于设计 /
处方优化 /
表征分析
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Key words
esomeprazole sodium /
solid dispersion /
QbD /
prescription optimization /
characterization analysis
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参考文献
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