目的 针对中药连续制造过程中制粒工艺的关键环节，探讨双螺杆湿法制粒（twin-screw wet granulation，TSWG）技术在桂枝茯苓胶囊（Guizhi Fuling Capsules，GFC）制粒过程中的应用。系统评估不同工艺参数对颗粒质量的影响，并优化工艺参数组合，以构建符合生产要求的TSWG工艺体系。方法 采用风险评估方法确定TSWG的关键影响因素，包括设备参数（双螺杆结构配置）和工艺参数（喂料质量流率、双螺杆质量流率、液固比等）。通过析因设计进一步分析工艺参数对颗粒物性参数的关键影响因素及其交互作用，通过Box-Behnken设计（Box-Behnken design，BBD）-响应面法（response surface methodology，RSM）构建了满足生产要求的TSWG工艺参数组合空间，筛选最优工艺参数组合，并与生产颗粒样品的物性参数进行比较与验证，以评价不同工艺参数组合对TSWG制粒性能的影响。结果 液固比及润湿剂乙醇体积分数对颗粒粒径、休止角等关键质量属性具有显著影响，而喂料质量流率和双螺杆质量流率对颗粒质量的影响相对较小。此外，TSWG颗粒能够满足生产要求，并且在控制颗粒松装密度和休止角的稳定性、改善颗粒流动性和溶化性方面表现出更优的性能。结论 系统优化了TSWG工艺参数，提高了GFC双螺杆湿法制粒工艺的可行性和成功率，为中药连续制造中的湿法制粒工艺提供了数据支持和优化方向。

Objective To investigate the application of twin-screw wet granulation (TSWG) technology in the granulation process of Guizhi Fuling Capsules (GFC, 桂枝茯苓胶囊), systematically evaluate the effects of process parameters on granule quality, and optimize parameter combinations to establish a TSWG process system meeting production requirements. Methods Critical influencing factors of TSWG, including equipment parameters (twin-screw configuration) and process parameters (feed mass flow rate, screw mass flow rate, liquid-to-solid ratio, etc.), were identified through risk assessment. A factorial design was employed to analyze the main and interactive effects of process parameters on granule physical properties. A Box-Behnken design (BBD) combined with response surface methodology (RSM) was used to construct a parameter space that meets production requirements, identify optimal parameter combinations, and compare the physical properties of TSWG granules with those of production batches for verification. Results Liquid-to-solid ratio and ethanol concentration in the binder had significant effects on key quality attributes such as particle size and angle of repose, while feed mass flow rate and screw mass flow rate had relatively minor effects. TSWG granules met production requirements and exhibited superior performance in maintaining bulk density and angle of repose stability, as well as improving flowability and dissolution behavior. Conclusion This study systematically optimized TSWG process parameters, enhancing the feasibility and success rate of twin-screw wet granulation for GFC, and providing data support and optimization strategies for wet granulation in continuous manufacturing of traditional Chinese medicines.

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开放基金课题（SKL2024Z0205）；北京中医药大学基本科研业务（揭榜挂帅）项目（2023-JYB-JBZD-060）