摘要
本研究旨在以"质量源于设计"(Quality by Design,QbD)理念为核心,应用热熔挤出3D打印技术制备对乙酰氨基酚缓释片,首先使用失效模式和效应分析法(failure mode and effects analysis,FMEA)进行因素风险评估,确定关键工艺参数(critical process parameters,CPPs),使用3中心点,23全因子实验设计,分析CPPs对关键质量属性(critical quality attributes,CQAs)的影响情况,以增塑剂用量、路径间距和外壳层数为实验设计的自变量,通过结果分析得出设计空间,增塑剂含量为9%,外壳层数为3~5层,路径间距为1.05~1.2 mm。本研究利用3D打印技术,遵循QbD理念进行对乙酰氨基酚缓释片的处方工艺优化,提高了工艺的耐用性,保证了制剂质量的均一可控,并为个体化给药提供了实验依据。
The aim of this study is to prepare acetaminophen sustained-release tablets by hot melt extrusion3 D printing technology based on the concept of"Quality by Design"(QbD).Firstly,the failure mode and effect analysis(FMEA)was used to determine the critical process parameters(CPPs),then full-factor experimental design was used to analyze the critical quality attributes(CQAs)and to establish the design space.The results showed that the content of plasticizer,the path spacing and the shell numbers are independent variable for the experimental design.The design space was concluded to be plasticizer content:9%,and the shell number:3-5,the path spacing:1.05-1.2 mm.In this study,3 D printing technology was used to prepare acetaminophen sustained-release tablets in accordance with the concept of QbD,which improved the durability of the process and ensured the uniform and controllable quality of the preparation and also provided experimental basis for personalised medicine.
作者
刘伯石
王增明
张慧
高静
刘楠
高翔
李蒙
郑爱萍
LIU Bo-shi;WANG Zeng-ming;ZHANG Hui;GAO Jing;LIU Nan;GAO Xiang;LI Meng;ZHENG Ai-ping(Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;93152 Unit Hospital of Chinese People's Liberation Army,Tonghua 134000,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第11期2719-2727,共9页
Acta Pharmaceutica Sinica
基金
重大新药创制科技重大专项(2018ZX09721003)。
关键词
计算机辅助设计
热熔挤出
3D打印
对乙酰氨基酚
缓释制剂
个体化给药
computer aided design
hot melt extrusion
three-dimensional printing
acetaminophen
sustained release preparation
personalised medicine