| “质量源于设计”在制备N-乙酰半胱氨酸注射液中的应用 |
| 投稿时间：2019-03-03 修订日期：2019-04-28 点此下载全文 |
| 引用本文：张莉燕,宋金春.“质量源于设计”在制备N-乙酰半胱氨酸注射液中的应用[J].药学实践杂志,2019,37(6):552~558 |
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| 中文摘要:目的 基于质量源于设计（quality by design，QbD）理念优化N-乙酰半胱氨酸（NAC）注射液的处方及制备工艺。方法 以QbD理念为核心，通过查阅文献获得关键质量属性（critical quality attributes，CQAs），采用鱼骨图结合失效模式与效应分析法（failure mode and effects analysis，FMEA）筛选影响注射液质量的关键工艺参数（critical process parameters，CPPs），使用Minitab软件进行试验设计，建立设计空间。结果 以灭菌前后pH值变化量，以主药含量为评价指标，通过鱼骨图结合FEMA确定了依地酸钙钠添加量、配液温度和灭菌条件为影响实验结果的关键工艺参数，方差分析结果显示建立的工艺参数与评价指标的数学模型P值均小于0.05，表明预测能力较好，得到的最佳参数为：依地酸钙钠添加量0.049 192%，最佳配液温度60℃，灭菌条件116℃，40 min。结论 基于QbD理念设计的NAC注射液处方合理，工艺参数稳定，建立的设计空间提高了工艺的耐用性，保证了制剂质量的均一可控。 |
| 中文关键词:质量源于设计 N-乙酰半胱氨酸 试验设计 |
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| Preparation of N-acetylcysteine injection based on quality by design |
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| Abstract:Objective To optimize the formulation and preparation technology of N-acetylcysteine(NAC) injection based on the concept of quality by design(QbD).Methods Using QbD as the guidance,the critical quality attributes affecting the quality of the injection were determined through literature and the critical process parameters were determined by fishbone diagram and failure mode and effects analysis.Minitab was applied to design experiments and analyze results and design space was established.Results The evaluation indexes were the pH changes before and after sterilization and the concent of NAC.The addition of sodium calcium edetate,preparation temperature and sterilization condition were determined as the critical quality attributes by fishbone diagram and FMEA.The results of variance analysis showed that the P value of the established mathematical models of the process parameters and evaluation indexes were less than 0.05,which indicated that the models had good prediction ability.The optimal parameters were the addition amount of calcium edetate was 0.049 192%,the preparation temperature was 60℃,and the sterilization condition was 116℃,40 min.Conclusion The prescription was reasonable,the process was stable and the established design space based on the concept of QbD improved the durability of the process and ensured uniform and controllability of the quality of the injection. |
| keywords:quality by design N-acetylcysteine design of experiment |
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