质量源于设计在盐酸多巴酚丁胺注射液处方工艺研究中的应用  

Application of Quality by Design Approach on the Development of Dobutamine Hydrochloride Injection

作　　者：李杨 周芳冰 耿爽 彭昱晖 Li Yang;Zhou Fangbing;Geng Shuang;Peng Yuhui(School of Pharmacy,Jinzhou Medical University;Jinzhou Avanc Pharmaceutical Co.,Ltd,Jinzhou 121000 China)

机构地区：[1]锦州医科大学药学院 [2]锦州奥鸿药业有限责任公司,辽宁锦州121000

出　　处：《锦州医科大学学报》2024年第1期32-38,共7页Journal of Jinzhou Medical University

摘　　要：目的基于质量源于设计(quality by design,QbD)的理念,建立仿制药盐酸多巴酚丁胺注射液目标产品质量概况(quality target product profile,QTPP),确定目标产品的关键质量属性(critical quality attributes,CQA),制定药液pH值的控制策略,优化灌装工艺以控制自研品顶空残氧量。方法方案设计药液pH值为2.0、2.5、3.3、4.0和5.5,对制备的样品放置影响因素,考察不同药液pH值对制剂质量的影响。以灌装速度、灌装前后的氮气流速、加塞前以及加塞中的氮气流速为自变量,实测残氧量为因变量进行3个中心点的1/2部分因子试验,对灌装充氮工艺进行优化。结果pH值2.5~5.5范围内各样品性状和溶液的澄清度与颜色、总杂及各单杂均未变化,样品质量稳定。确定灌装线的充氮参数和灌装速度的最佳空间40%~67%。结论本实验研究确定了仿制药盐酸多巴酚丁胺注射液的pH值控制范围以及最佳灌装充氮工艺参数,合理可行,可较好控制产品质量。Objective Based on the concept of quality by design(QbD),to establish the quality target product profile(QTPP)of generic dobutamine hydrochloride injection,determine the critical quality attributes(CQA)of the target product,develop the control strategy of pH value of the liquid medicine,and optimize the filling process to control the residual oxygen in the top space of the self-developed product.Methods The pH values of the solution were 2.0,2.5,3.3,4.0 and 5.5.Stress testing was conducted to further explore the effect of pH value of different liquid on the quality of the preparation.With filling speed,nitrogen flow rate before and after filling,nitrogen flow rate before and during plugging as independent variables,and the measured residual oxygen as dependent variable,a partial factor test of 1/2 of 3 central points was performed and the nitrogen filling process was optimized.Results In the range of pH value 2.5-5.5,the properties of each sample,the clarity and color of the solution,the total impurity and each single impurity did not change,and the quality of the sample was stable.The best space of nitrogen filling parameters and filling speed of filling line 40%-67%were determined.Conclusion In this study,the pH value control range and the optimal nitrogen filling process parameters of generic dobutamine hydrochloride injection were determined,which were reasonable and feasible,and could better control product quality.

关 键 词：盐酸多巴酚丁胺注射液 质量源于设计 处方工艺 注射液 

分 类 号：R94[医药卫生—药剂学]