目的 以桂枝茯苓胶囊（Guizhi Fuling Capsules，GFC）制药过程浓缩工艺为研究对象，通过解析“功效物质-物性参数-工艺参数”的相关性，确定关键质量属性与关键工艺参数，探究质量控制指标及其控制范围，挖掘以中间体物性参数为导向的质量控制潜能。方法 系统考察浓缩过程工艺参数（浓缩温度、浓缩终点相对密度）、物性参数（粒径、多分散指数、ζ电位、电导率、pH值、黏度、折光率）及功效物质、固体总量的变化规律。利用Pearson相关系数、灰色关联度及偏最小二乘法等化学计量学方法，并通过建立浓缩过程不同工艺参数下功效物质与物性参数的线性模型，阐明功效物质-物性参数-工艺参数的相关性。结果 通过功效物质含量及物性参数分析，发现ζ电位、电导率、黏度、固体总量均与功效物质的含量具有较强相关性，如黏度与固体总量呈正相关，苦杏仁苷、芍药苷的含量与固体总量均呈正相关。对不同工艺参数下样品的功效物质与物性参数进行分析，发现浓缩温度为影响功效物质及物性参数相关性的关键因素。结论 通过对工艺参数、物性参数以及功效物质的关联性分析发现，不同的变量之间存在相互作用和动态传递过程，在生产过程中需精准控制浓缩温度以提高浸膏的品质及其批间质量均一性；在一定程度上，可使用黏度、相对密度、折光率、pH值等物性参数反映浓缩工序中间体的质量，为中药提取液浓缩环节在线智能监测提供参考。

Objective This study focused on the concentration process in the manufacturing of Guizhi Fuling Capsules (GFC, 桂枝茯苓胶囊). By analyzing the correlations among effective components, physical properties, and process parameters, it aimed to identify critical quality attributes (CQAs) and critical process parameters (CPPs), explore quality control indicators and their acceptable ranges, and assess the potential for using physical properties of intermediate to guide its quality control. Methods The variations in process parameters (temperature, relative density at endpoint), physical properties (particle size, polydispersity index, ζ potential, conductivity, pH value, viscosity and refractive index), and effective components and total solid content during the concentration process were systematically investigated. Chemometric methods, including Pearson correlation coefficient, grey relational analysis, and partial least squares regression, were applied. Linear models between effective components and physical properties under different process parameters were established to elucidate the correlations among them. Results Analysis of effective component content and physical properties revealed strong correlations between effective components and ζ potential, conductivity, viscosity, and total solids content. For instance, viscosity was positively correlated with total solids, and the contents of amygdalin and paeoniflorin were both positively correlated with total solid content. Analysis of the active ingredients and physical property parameters of samples under various process parameters revealed that the concentration temperature is a key factor influencing the correlation between active ingredients and physical property parameters. Conclusion Correlation analysis of process parameters, physical properties, and effective components revealed interactive and dynamically linked relationships among these variables. Precise control of the concentration temperature during the manufacturing is essential to improve the quality and batch-to-batch consistency of the extract. To a certain extent, parameters such as viscosity, relative density, refractive index and pH value can reflect the quality of intermediates during concentration, providing a reference for the development of online intelligent monitoring in the concentration process of traditional Chinese medicine extracts.

R283.6

国家长三角科技创新共同体联合攻关项目（2023CSJGG1700）；中药制药过程控制与智能制造技术全国重点实验室定向课题（SKL2023D02002）；江苏省基础研究计划——青年基金项目（BK20250552）；连云港市重点研发计划（CG2320）