摘要
目的探讨处方中的辅料及工艺对阿普唑仑片混合均匀度及含量均匀度的影响。方法采用粉末直接压片法制备低剂量阿普唑仑片,以总混物料的混合均匀度及含量均匀度为评价指标,通过单因素试验,考察处方中辅料型号与用量、工艺中原料药粒度及混合工艺、压片工艺对混合均匀度及含量均匀度的影响。结果采用圆形形貌和粗糙表面的喷雾干燥型乳糖(11SD,F100),微晶纤维素型号(PH102,PH200,TLF935),玉米淀粉用量(3%,5%,7%),胶态二氧化硅用量(0.8%,1.2%)的处方混合均匀度的RSD远低于5%,含量均匀度(A+2.2 S)远低于15.0;采用原料药粒径D90不大于35μm,阿普唑仑与乳糖先通过湿法制粒机以600 r/min预混10 min,之后转移至三维运动混合机中,并加入微晶纤维素、玉米淀粉、胶态二氧化硅,在混合频率12 Hz下混合15~25 min的工艺的混合均匀度的RSD低于2.5%;采用压机转速10~20 r/min的含量均匀度(A+2.2 S)低于7.2。结论优选的处方工艺适用于阿普唑仑片的含量均匀度和质量控制,可用于工业化生产。
Objective To investigate the effects of excipients and processes in the formulation on the blend uniformity and content uniformity of Alprazolam Tablets.Methods Low-dose Alprazolam Tablets were prepared by direct compression method.With the blend uniformity and content uniformity of the total mixed materials as evaluation indicators,the effects of the types and dosages of excipients,the blend technology and tablet technology on the blend uniformity and the content uniformity were investigated by the single factor test.Results The RSD of the blend uniformity of the formulation with round shape and rough surface of spray-dried lactose(11SD,F100),types of microcrystalline cellulose(PH102,PH200,TLF935),dosages of corn starch(3%,5%,7%),dosages of colloidal silica(0.8%,1.2%)was far lower than 5%,and the content uniformity(A+2.2 S)was far lower than 15.0.The particle size D90 of the active pharmaceutical ingredients(API)was no more than 35μm,the alprazolam and lactose were pre-blended by a wet granulator of 600 r/min for 10 min,and then transferred to a three-dimensional moving mixer,where microcrystalline cellulose,corn starch and colloidal silica were added and mixed at blending frequency of 12 Hz for 15-25 min,the RSD of blend uniformity was lower than 2.5%.The content uniformity(A+2.2 S)of tableting speed(10-20 r/min)was lower than 7.2.Conclusion The optimal formulation process is suitable for the content uniformity and quality control of Alprazolam Tablets,which can be used for industrial production.
作者
郭金秀
曾令高
高梓真
许向阳
陈醒
王家辉
GUO Jinxiu;ZENG Linggao;GAO Zizhen;XU Xiangyang;CHEN Xing;WANG Jiahui(Pharmaceutical Research Institute of Jiangsu Nhwa Pharmaceutical Co.,Ltd.·Jiangsu Provincial Key Laboratory of Central Nervous System Drugs,Xuzhou,Jiangsu,China 221100;Chongqing Institute for Food and Drug Control·NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances,Chongqing,China 401121)
出处
《中国药业》
CAS
2023年第23期18-23,共6页
China Pharmaceuticals
基金
国家“重大新药创制”科技重大专项资助项目[2015ZX093001002007,2017ZX09101001]。
关键词
阿普唑仑片
直接压片法
混合均匀度
含量均匀度
Alprazolam Tablets
direct compression
blend uniformity
content uniformity
