摘要
目的:建立阿瑞匹坦含量与溶出分析检测方法,以3种不同的制备方法(热熔挤出法、溶剂-熔融法、喷雾干燥法)制备阿瑞匹坦固体分散体,考察了不同工艺对该固体分散体物理稳定性的影响。方法:从该固体分散体的含水量和引湿性的测定、不同工艺制剂中残留微晶的测定、含量与有关杂质测定以及体外释放评价等角度出发,衡量不同制备工艺对阿瑞匹坦固体分散体稳定性的影响。结果:3种不同工艺中以热熔挤出法制备的阿瑞匹坦固体分散体含水量少、引湿性差,药物以无定形形式存在,体外溶出行为较好,能够在酸液中溶解释放,转运至肠道后能够抵抗pH改变而带来的析晶、沉淀行为并维持较高的过饱和度。结论:确定了结晶抑制剂醋酸羟丙甲基纤维素琥珀酸酯(HPMCAS)和溶出促进剂聚乙烯吡咯烷酮K30(PVP K30)组成的固体分散体的最优制备方法为热熔挤出法。
Objective:To establish an analytical method for determination of the content and dissolution of aprepitant,prepare aprepitant solid dispersion by three different preparation methods(hot-melt extrusion,solvent-melt method and spray drying method),and investigate the effects of different processes on the physical stability of the solid dispersions.Methods:The effects of different preparation processes on the stability of aprepitant solid dispersions were measured in terms of water content,moisture attraction,residual microcrystals,aprepitant content,related impurities,and in vitro release.Results:Among the three different processes,the aprepitant solid dispersion prepared by hot-melt extrusion had low water content,poor moisture attraction,drug in amorphous form,good in vitro dissolution behavior,able to dissolve and release in acid solution,resistant to crystallization and precipitation behavior due to pH change and maintained high supersaturation after transit to the intestine.Conclusion:Hot-melt extrusion is the optimal preparation method for solid dispersions composed of crystallization inhibitor HPMCAS and dissolution enhancer PVP K30.
作者
王冰茜
陈挺
杨静
WANG Bing-xi;CHEN Ting;YANG Jing(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Zhitong Biomedical Technology Co.,Ltd.,Shanghai 201203,China;East China University of Science and Technology,Shanghai 200237,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2023年第21期2191-2197,共7页
Chinese Journal of New Drugs
关键词
阿瑞匹坦
固体分散体
制备工艺
体外溶出
aprepitant
solid dispersion
preparation process
in vitro dissolution
