固体分散体制备技术及质量控制研究进展  

Research progress on preparation techniques and quality control of solid dispersions

作　　者：张晓阳 应泽华 郭抒博 李文龙 ZHANG Xiaoyang;YING Zehua;CUO Shubo;LI Wenlong(College of Pharmaceutical Engineering of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,301617,China;Haihe Laboratory of Modem Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,301617,China)

机构地区：[1]天津中医药大学中药制药工程学院,天津301617 [2]天津中医药大学现代中医药海河实验室,天津301617

出　　处：《中国粉体技术》2024年第2期96-112,共17页China Powder Science and Technology

基　　金：国家重点研发计划项目,编号:2023YFC3504502;国家自然科学基金项目,编号:82074276;现代中医药海河实验室科技计划项目,编号:22HHZYSS00004。

摘　　要：【目的】从固体分散体(solid dispersions,SDs)制备技术和质量控制角度出发,揭示SDs技术在药物制剂领域的发展现状与挑战,旨在为SDs技术的进一步推广应用提供参考。【研究现状】总结熔融法、溶剂法、溶剂-熔融法、机械分散法等SDs制备技术,其中熔融法又包括传统熔融法、热熔挤出法、熔融凝聚、KinetiSol~?Dispersing、3D打印技术等,溶剂法又包括喷雾干燥、冷冻干燥、流化床干燥、超临界流体法、共沉淀法和静电纺丝法等;目前SDs制备技术存在需要使用有毒溶剂,可能导致药物热降解以及扩展性较差的问题。并归纳总结溶出度、药物和聚合物之间的相互作用、固态等SDs质量控制因素,重点强调一直被研究人员忽视的SDs粉体学性质。【展望】认为今后的研究重点应在开发或引入更多高效、无毒、稳定和扩展性好的SDs制备技术方面,并且要不断完善SDs的质量控制体系。Significance Drug solubilization is an essential step for orally administered medications to be absorbed systemically. Unfortunately, many drugs have poor water solubility, which severely limits their clinical applications. During drug Research & Development, various methods have been tried to overcome the poor water solubility of drug candidates, including salt formation, micritization, solid-lipid nanoparticles, nanosuspensions, and solid dispersions(SDs). Among them, SDs technology stands out for the advantages of simplicity, rapidity, and maturity, making it oone of the most successful strategies for improving the dissolution properties of insoluble drugs. SDs. Hence, SDs have emerged as a hot research topic in the past decade.Progress So far, many techniques have emerged for the preparation of SDs, which are derived from the following methods, including the melting method, solvent method, melt-solvent method, and milling-based method. Among them, melt-based hot melt extrusion technology(HME) has gained prominence as a solvent-free, commercially scalable method for various drug delivery systems. Additionally, spray drying technology known for its extremely fast solvent removal efficiencies and good scale-up capabilities, has become the most popular solvent method. The fluidized bed drying method stands out for its ability to prepare SDs with both good flowability and dissolution properties. Furthermore, 3D printing technology offers the advantages in personalization and dosage form customization for pharmaceutical production. Despite the availability of these techniques, the selection of appropriate preparation techniques for SDs remains a challenge due to the complex and variable physicochemical properties of APIs and polymers as well as the lack of in-depth knowledge of the preparation techniques. Although many drug products based on SDs technology have been successfully marketed since 1989, the current quality control of SDs was still limited to the solid state, drug-polymer interactions, and dissolution,

关 键 词：固体分散体 制备技术 热熔挤出 3D打印 喷雾干燥 流化床 质量控制 粉体学性质 

分 类 号：TB4[一般工业技术] R943[医药卫生—药剂学]