金贝口服液制备过程中指标成分黄芪甲苷的传递研究

Study on Transfer of Index Component AstragalosideⅣin Preparation of Jinbei Oral Solution(金贝口服液)

目的:研究金贝口服液制备过程中黄芪主要活性成分——黄芪甲苷的转移率变化情况,探讨影响金贝口服液指标成分传递的工艺因素,优化金贝口服液生产工艺,进一步明确关键工序及关键参数。方法:制备金贝口服液样品,制备工艺含提取-浓缩-乙醇沉淀(醇沉)-水沉-配液-灌装-灭菌等,对各工序药液取样,检测试样中黄芪甲苷的含量并计算其转移率;根据黄芪甲苷转移率确定影响金贝口服液指标成分传递的主要因素并进行关键参数研究,优化金贝口服液生产工艺。结果:金贝口服液制备过程中影响黄芪甲苷量值传递的关键工序是醇沉和灭菌。多批次研究显示,醇沉工序中黄芪甲苷相对前一工序转移率分别是78.34%~90.08%,平均转移率83.99%;灭菌工序中黄芪甲苷相对前一工序转移率分别是75.61%~78.93%,平均转移率77.15%;其他工序均大于90%。通过对加乙醇速度、搅拌速度、醇沉温度优化研究确定醇沉工序加乙醇速度50 mL/s,搅拌速度600 r/min,醇沉温度(2±1)℃;通过对灭菌前配制液酸碱度、灭菌温度和灭菌时间的优化研究确定灭菌前配制液pH值为6.00±0.05,灭菌温度105℃,灭菌时间30 min。结论:本研究优化了金贝口服液制备过程中的醇沉参数、配液参数及灭菌参数;提示在新药研究及产品生命周期内均应持续加强关键工艺及关键参数的优化研究,持续加强生产过程的精细化控制水平,提高产品质量控制能力。

Objective:To study the transfer rate changes of the main active ingredient(AstragalosideⅣ)of Huangqi(Astragali Radix)during the preparation of Jinbei Oral Solution(金贝口服液),toexplore the technological factors affecting the transfer of the index components of Jinbei Oral Solution,to optimize the production process of Jinbei Oral Solution,and to further clarify the key processes and parameters.Methods:Samples of Jinbei Oral Solution were prepared.The preparation process included extraction,concentration,ethanol precipitation(alcohol precipitation),water precipitation,liquid preparation,filling and sterilization.Samples were taken from the liquid in each process to detect the content of AstragalosideⅣin the sample and calculate the transfer rate of AstragalosideⅣ.According to the transfer rate of astragalosideⅣ,the main factors affecting the component transfer of Jinbei Oral Solution were determined and the key parameters were studied to optimize the production process of Jinbei Oral Solution.Results:The results showed that alcohol precipitation and sterilization processes were the main processes affecting the value transfer of AstragalosideⅣin the preparation.Several batches of study showed that the transfer rates of AstragalosideⅣin alcohol precipitation process were 78.34%~90.08%with an average transfer rate of 83.99%;the transfer rates of AstragalosideⅣin sterilization process were 75.61%~78.93%with an average transfer rate of 77.15%;other processes were all greater than 90%.The optimization study on the ethanol adding speed,stirring speed and ethanol precipitation temperature determined the ethanol adding speed of 50 mL/s,stirring speed of 600 r/min and ethanol precipitation temperature of(2±1)℃.The optimal study on the pH value of the prepared solution before sterilization,the sterilization temperature and the sterilization time determined that the pH value of the prepared solution before sterilization was 6.00±0.05,the sterilization temperature was 105℃,and the sterilization time was 30 min.Conclusions:In this study,alcohol precipitation parameters,liquid dispensing parameters and sterilization parameters of Jinbei Oral Solution were optimized.It fully reflects that the optimization of key processes and key parameters should be continuously strengthened in the new drug research and the product life cycle,and the refined control level of the production process should be continuously strengthened to improve the product quality control ability.