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中药干法制粒工艺放大关键技术瓶颈与多尺度数字建模应用研究进展

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中草药 | 综述 2026,57(17): 6985-6997

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中草药 |综述 2026 , 57 (17) : 6985 -6997

中药干法制粒工艺放大关键技术瓶颈与多尺度数字建模应用研究进展

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管咏梅^1,2, 赵子波^1,2, 刘乐灵^1,2, 杨明^1,2, 李糯柔¹, 易秀^1,2, 臧振中¹

作者信息

通讯作者:

臧振中

作者简介:

管咏梅: 管咏梅，教授，博士生导师，从事中药新制剂与新技术研究。E-mail:guanym2008@163.com

Key technical bottlenecks in process scale-up of traditional Chinese medicine dry granulation and application of multi-scale digital modeling

GUAN Yongmei^1,2, ZHAO Zibo^1,2, LIU Leling^1,2, YANG Ming^1,2, LI Nuorou¹, YI Xiu^1,2, ZANG Zhenzhong¹

Affiliations

doi: 10.7501/j.issn.0253-2670.2026.17.028

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摘要

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工艺放大是制剂由研发向工业化生产转化的核心环节。干法制粒作为中药固体制剂成型的关键技术，具有工序短、对有效成分影响小、高效节能等优势。但其工艺放大过程面临诸多挑战。综述了中药干法制粒工艺放大的关键技术瓶颈，包括关键工艺参数、送料系统与设备热力学效应，及关键物料属性。从方法论支撑与策略演进2个维度，归纳了放大策略从传统经验放大到数字建模驱动的多尺度智能放大的演进脉络。其中，灰箱混合建模、基于群体平衡模型的全流程集成模拟及过程分析技术驱动的闭环反馈控制，为破解放大过程中的非线性问题提供了新思路。未来，融合物理指纹图谱与数字孪生技术构建跨尺度放大框架，推动工艺研发从“经验驱动”向“模型驱动”转型，助力中药制药实现智能制造的战略升级。

关键词

干法制粒 / 工艺放大 / 物理指纹图谱 / 数字建模 / 连续制造 / 质量源于设计

Abstract

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Process scale-up is a critical step in the transition of pharmaceutical preparations from research and development to industrial production. Dry granulation, as a key technology for forming traditional Chinese medicine (TCM) solid dosage forms, offers advantages such as a short process flow, minimal impact on active ingredients, high efficiency, and energy savings. However, its process scale-up faces numerous challenges. This article reviews the key technical bottlenecks in the process scale-up of TCM dry granulation, including critical process parameters, thermodynamic effects of the feeding system and equipment, and critical material attributes. The evolution of scale-up strategies is summarized from perspectives of methodological support and strategic evolution, tracing the progression from traditional empirical scale-up to digital modeling-driven multi-scale intelligent scale-up. Among these, gray-box hybrid modeling, population balance model-based integrated process simulation, and process analytical technology-driven closed-loop feedback control offer new approaches to address nonlinear issues during scale-up. In the future, integrating physical fingerprint with digital twin technology to establish a cross-scale scale-up framework will promote the transformation of process development from “experience-driven” to “model-driven” paradigms, thereby facilitating the strategic upgrade of TCM pharmaceutical manufacturing toward intelligent manufacturing.

Key words

dry granulation / process scale-up / physical fingerprint / digital modeling / continuous manufacturing / quality by design

引用本文

管咏梅, 赵子波, 刘乐灵, 杨明, 李糯柔, 易秀, 臧振中. 中药干法制粒工艺放大关键技术瓶颈与多尺度数字建模应用研究进展. 中草药, 2026 , 57 (17) : 6985 -6997 . DOI: 10.7501/j.issn.0253-2670.2026.17.028

GUAN Yongmei, ZHAO Zibo, LIU Leling, YANG Ming, LI Nuorou, YI Xiu, ZANG Zhenzhong. Key technical bottlenecks in process scale-up of traditional Chinese medicine dry granulation and application of multi-scale digital modeling[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (17) : 6985 -6997 . DOI: 10.7501/j.issn.0253-2670.2026.17.028

基金

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江西省自然科学基金资助项目 (20252BAC240049); 全国重点实验室自主部署重点研发计划项目 (20243BCC31010); 江西中医药大学科技创新团队项目 (CXTD22006); 2025年度江西中医药大学校级研究生创新专项 (XJ-S202539)

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2026年第57卷第17期

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doi: 10.7501/j.issn.0253-2670.2026.17.028

接收时间：2026-04-11
首发时间：2026-10-29

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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