摘要
目的优化五味益心颗粒成型工艺,并构建其物理指纹图谱。方法采用D-最优混料设计以颗粒一次成型率、溶化率、吸湿率(H)、休止角(α)为考察指标筛选最佳辅料比例;采用Box-Behnken实验结合AHP-CRITIC混合加权法优化干法制粒机工艺参数;建立由松装密度(Da)、振实密度(Dc)、α、豪斯纳比(IH)、H、含水量(HR)、颗粒间孔隙率(Ie)、卡尔指数(IC)、比表面积(SSA)、粒径<50μm百分比(Pf)、分布宽度(Span)、分布范围(Width)、均匀性(HG)共13个颗粒物性指标构建物理指纹图谱,评价批次间颗粒质量的相似性。结果五味益心颗粒辅料最佳比例:糊精49%、麦芽糊精23%、可溶性淀粉28%;最佳制粒工艺参数:输料转速64.1 r·min^(−1)、压轮转速6.7 r·min^(−1)、液压压力6.1 MPa;15批样品物理指纹图谱相似度均大于0.99。结论优化后干法制粒工艺稳定可行,可为后续中试放大以及大生产提供参考。
Objective Optimize the forming process of Wuwei Yixin Granules and construct its physical fingerprint.Methods The D-optimal mixture design was used to screen the best excipient ratio with the primary forming rate,melting rate,moisture absorption rate and angle of repose of the particles as the indexes.The process parameters of dry granulator were optimized by Box-Behnken experiment combined with AHP-CRITIC hybrid weighting method,the physical fingerprint of the granules consisting of 13 secondary physical quality indexes,including bulk density(Da),tap density(Dc),α,Hausner ratio(IH),H,water content(HR),interparticle porosity(Ie),Karl index(IC),specific surface area(SSA),particle size<50μm percent(Pf),Span,Width and homogeneity(HG),was established to evaluate the consistency of granule quality among different batches.Results The best proportion of excipients of Wuwei Yixin Granules:dextrin 49%,maltodextrin 23%,soluble starch 28%.The best granulation process parameters:feeding speed 64.1 r·min^(−1),pressure wheel speed 6.7 r·min^(−1),hydraulic pressure 6.1 Mpa.The physical fingerprint had good similarity between 15 batches.Conclusion The optimized dry granulation process is stable and feasible,which can provide reference for subsequent pilot scale-up and large-scale production.
作者
张泽宇
陶振
王佳
王星星
王振中
ZHANG Zeyu;TAO Zhen;WANG Jia;WANG Xingxing;WANG Zhenzhong(State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture(Jiangsu Kanion Pharmaceutical Co.,Ltd.,&Nanjing University of Chinese Medicine),Nanjing 210000,China;Kanion School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China)
出处
《药物评价研究》
北大核心
2025年第3期698-707,共10页
Drug Evaluation Research
基金
国家长三角科技创新共同体联合攻关项目(2023CSJGG1700)。
