原辅料粉体学性质对片剂连续制造的影响  

Influence of powder properties of pharmaceutical ingredients on continuous tablet manufacturing

作　　者：徐浩原 任曼华 何显洪 陈蕾[2] 张欣 关健 毛世瑞[1] XU Haoyuan;REN Manhua;HE Xianhong;CHEN Lei;ZHANG Xin;GUAN jian;MAO Shirui(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Chinese Pharmacopoeia Commission,Beijing 100061,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]国家药典委员会,北京100061

出　　处：《中国粉体技术》2024年第6期97-118,共22页China Powder Science and Technology

基　　金：国家重点研发计划项目,编号:2020YFE0201700;国家药品标准修订研究课题项目,编号:2022Y15,2023Y38。

摘　　要：【目的】推进片剂连续制造技术的发展,分析粉体学性质在片剂连续制造中的重要性,进一步提升片剂连续制造的致密性和均匀性。【研究现状】综述物料输送、连续进料、连续混合、连续压片、连续辊压制粒、连续双螺杆制粒、连续流化床干燥等工艺过程,概括各工艺过程中使用的过程分析技术(process analytical technology,PAT)及监测工具,阐述原辅料粉末的关键原料特性对工艺过程和片剂关键质量属性的影响。【结论与展望】提出应当对具有多变性质的原辅料进行全面表征,预测流动性和成形性,建立物料库并进行分类,有利于选择工艺参数、优化工艺性能、完善处方设计;认为重视原辅料粉体性质并建立预测模型有利于减少裂片、含量不均匀等质量问题及堵塞、黏壁等生产问题。Significance Continuous manufacturing is the future trend in tablet manufacturing.In order to accelerate the development of continuous tablet manufacturing,this article analyzes the influence of powder properties of pharmaceutical ingredients on continuous manufacturing.An in-depth understanding of powder properties enhances tablet quality,as well as the efficiency and homogeneity of continuous tablet manufacturing.Progress So far,three main methods of continuous tablet manufacturing have improved production capability:continuous direct compression,continuous wet granulation,and continuous dry granulation.Among these,due to the limited number of unit operations involved,continuous direct compression has become the most popular method of continuous tablet manufacturing.Compared to batch manufacturing,continuous tablet manufacturing integrates unit operations,including loss-in-weight feeders,continuous mixers,continuous tablet press,roller compactor,twin-screw granulation(TSG),and fluidized bed drying.The powder properties of pharmaceutical ingredients play a pivotal role in these unit operations,affecting flow behavior and tablet quality.During the continuous direct compression process,the physical properties of the powder,such as density,particle size,and particle shape,affect the flowability of powders,which in turn impacts feedability,mixing uniformity,and hence the drug content of the final tablet.Flowability can be characterized by emerging technologies such as shear testing or traditional static tests,such as the angle of repose and Carr's index.The compression mechanism of the material,such as brittle or plastic deformation,moisture content,and crystal habit,affects the compressibility and compactibility of the material.Powders with good compressibility and compactibility can be used to obtain tablets with a smooth appearance and sufficient hardness through appropriate process parameters.Compressibility and compactability can be evaluated using mathematical equations such as Heckel's equation,Shapiro's equa

关 键 词：片剂 连续制造 粉体学性质 单元操作 过程分析技术 

分 类 号：R944[医药卫生—药剂学]