羧甲淀粉钠来源差异对其性质及其功能的影响  

Effects of source difference of sodium carboxymethyl starch on its properties and function

作　　者：郝敬强 杨白雪 孙微 孙瑞濛 孙会敏[2] 李三鸣[1] HAO Jing-qiang;YANG Bai-xue;SUN Wei;SUN Rui-meng;SUN Hui-min;LI San-ming(Shenyang Pharmaceutical University,Shenyang 110016,China;National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]沈阳药科大学,辽宁沈阳110016 [2]中国食品药品检定研究院,北京100050

出　　处：《药学学报》2020年第5期1022-1029,共8页Acta Pharmaceutica Sinica

基　　金：国家科技重大专项资助项目(2017ZX0901001-006-012).

摘　　要：一致性评价中发现,仿制药与原研药体外释放一致并不足以说明体内释放的一致,作为片剂药物释放的前提,片剂的崩解极大影响了药物释放情况,而这些与崩解剂的结构性质密切相关,因此崩解剂的系统性研究对仿制药一致性评价具有重要意义。本实验考察了9个厂家11种羧甲淀粉钠(carboxymethyl starch sodium, CMS-Na)的理化性质及应用性能,为一致性评价中的辅料选择提供参考。采用扫描电子显微镜观察粒子形态;干法粒度仪测定粒径分布;按照2015版中国药典方法测定羧甲淀粉钠pH值和干燥失重;通过卡尔指数(Carr’s指数)、豪森比(Hausner比)和休止角评价粉体的流动性;以吸水性和溶胀性为评价指标,评价羧甲淀粉钠的崩解性能。分别以乳糖和微晶纤维素为填充剂,研究羧甲淀粉钠的崩解效果。结果显示,所有产品pH值和干燥失重均符合要求,但粒子形态、流动性、吸水溶胀性及崩解时限等差异较大,导致不同来源的羧甲淀粉钠性质及片剂崩解差异性较大。可见若要保证仿制药与原研药完全一致,在处方前研究中,合理选择崩解剂才能确保良好的批间重现性。During the process of consistency evaluation, it was found that the consistency of drug release between generic and original brands in vitro was not sufficient to demonstrate their same release in vivo. The disintegration of tablets, as a premise for the release of tablet drugs, greatly affects the release of drugs, depending on the structure and properties of disintegrants. Hence the systematic research on disintegrants would be very important for the evaluation of generic consistency. In this experiment, the physicochemical properties and application of 11 different sodium carboxymethyl starch(CMS-Na) from 9 manufacturers were investigated. This provides the reference for selection of excipients for consistency evaluation. The particle morphology of CMS-Na was observed by scanning electron microscope. The particle size distribution was determined by dry particle size analyzer. The determination of pH and loss on drying was carried out according to the 2015 edition of Chinese pharmacopoeia method. The powder fluidity was evaluated with Carr’s index, Hausner ratio and angle of repose.The disintegration performance of CMS-Na was evaluated through determining the water absorption and swelling.The disintegration effect of CMS-Na tablets was studied using lactose and microcrystalline cellulose as fillers. The results showed that pH values and weight loss on drying of all samples met the requirements, whereas the particle morphology, fluidity, water swell-ability and disintegration time had a large variation, which leads to the large differences the properties of CMS-Na depending on the sources. Therefore in order to ensure that the reproducibility of generic drugs from their name brand, our studies indicate that only a sizable choice of disintegrants could ensure good inter batch reproducibility.

关 键 词：一致性评价 羧甲淀粉钠 流动性 吸水性 溶胀性 

分 类 号：R943[医药卫生—药剂学]