目的:建立激光散射法湿法测定利伐沙班原料药粒度分布并进行方法学验证。方法:采用Malvern Mastersizer 2000 型激光粒度分析仪,Hydro 2 000 MU 湿法进样器,分散介质为水,聚山梨酯 20 作为分散剂, 超声强度20 MHz,超声50 s,浆液循环泵转速2 100 r·min-1,背景与样品扫描时间10 s,测量次数4 次。结果:样品折射率1.633,样品吸光率0.1,遮光率8%~15%。方法学考察结果粒度分布值d(0.9)的RSD 均小于2%;6 批利伐沙班原料药样品粒径分布特征值均符合d(0.9)应为9~15 μm 的企业质量标准规定。结论:本方法准确、快速,重现性好,适合利伐沙班原料药的粒度测定。
Objective: To establish a laser light scattering method(wet) for the determination of particle size and distribution of rivaroxaban active pharmaceutical ingredient (API). Methods: The Malvern Mastersizer 2000 laser size analyzer with the Hydro 2000 MU wet autosampler were used. The determination conditions:dispersion medium was water. Dispersant was Tween-20. Samples were evenly dispersed by ultrasonic(20 MHz) for 50 s. Measurement time for background and specimen were 10 s. Determination were conducted 4 times. Results: Particle refractive index was 1.633,granule absorbency was 0.1,laser obscuration was 8%~15% and the speed of slurry circulation pump was 2100 r·min-1. The RSD of d(0.9)was less than 2%. All the d(0.9) values of 6 batches rivaroxaban API were 9-15 μm,which were in accordance with the manufacturer's internal standard. Conclution: The method is accurate,fast and repeatable. It is suitable for the particle size determination of rivaroxaban API.
[1] 王华伟,喻明,李晓斌,等.利伐沙班片在中国健康志愿者中的生物等效性研究[J]. 中国临床药理学杂志,2020,36(22):3590
WANG HW,YU M,LI XB,et al.Bioequivalence of rivaroxaban tablets in healthy Chinese subjects[J]. Chin J Clin Pharmacol, 2020,36(22):3590
[2] 罗新鹏. 三类新药利伐沙班的质量标准研究[D]. 武汉:武汉工程大学,2015
LUO XP.The Quality Standard On III type New-drug Rivaroxaban[D]. Wuhan:Wuhan Institute of Technology,2015
[3] 陈祝康,陈桂良,李慧义. 药物及其制剂粒度测定法探讨[J]. 中国药品标准,2012,13(6):405
CHEN ZK,CHEN GL,LI HY.Discussion about particle size analysis for drug and pharmaceuticals[J]. Drug Stand China, 2012,13(6):405
[4] 方亮. 药剂学[M]. 第8 版. 北京:人民卫生出版社,2016:172
FANG L.Pharmacy[M]. 8th Ed. Beijing:People's Medical Press, 2016:172
[5] 谷广智,王也牧,刘蔚,等.依非韦伦原料药的激光散射法测定[J]. 中国医药工业杂志,2016,47(1):67
GU GZ,WANG YM,LIU W,et al.Determination of efavirenz particle size by laser light scattering method[J]. Chin J Pharm, 2016,47(1):67
[6] 狄天云,高原雨,朱捷,等.激光粒度仪测定醋酸肤轻松乳膏粒度的方法学研究[J]. 药物分析杂志,2016,36(1):181
DI TY,GAO YY,ZHU J,et al.Methodological study of particle size of fluocinonide cream by laser particle analyzer[J]. Chin J Pharm Anal,2016,36(1):181
[7] 邹文博,许明哲,王晨,等.激光散射法测定的乳糖的粒度[J]. 药物分析杂志,2007,27(9):1420
ZOU WB,XU MZ,WANG C,et al.Measurement of particles size distribution of lactose by laser light scattering method[J]. Chin J Pharm Anal,2007,27(9):1420
[8] 丁怡,章娟.激光粒度仪测定曲安奈德注射液粒度[J]. 药物分析杂志,2017,37(11):2038
DING Y,ZHANG J.Determination of particle size of triamcinolone acetonide injection by laser scattering analyzer[J]. Chin J Pharm Anal,2017,37(11):2038
[9] 秦士慧,冯中,张贵民.帕博昔布原料药粒径的激光散射法测定[J]. 中国医药工业杂志,2017,48(8):1203
QIN SH,FENG Z,ZHANG GM.Application of laser particle size analyzer in measurement of palbociclib partical size distribution[J]. Chin J Pharm,2017,48(8):1203
[10] 中华人民共和国药典 2015 年版.二部华人民共和国药典 2015 年版.二部[S]. 2015:361
ChP 2015.Vol ⅡhP 2015.Vol Ⅱ[S]. 2015:361
[11] 陈继敏,欧金泉,潘京.激光散射法测定普伐他汀钠原料药粒度分布[J]. 今日药学,2016,26(5):314
CHEN JM,OU JQ,PAN J.Measurement of particle size distribution of pravastatin sodium by laser light scattering method[J]. Pharm Today,2016,26(5):314
[12] 邹文博,王琰,尹利辉,等.应用激光散射法测定西洛司特粒度分布[J]. 药学研究,2018,37(2):93
ZOU WB,WANG Y,YIN LH,et al.Particlesize distribution analysis of cilomilast using laser diffraction method[J]. J Pharm Res,2018,37(2):93
[13] 耿志鹏,姜鹰雁,李永东,等. 缬沙坦原料药粒度的激光散射法测定[J]. 中国医药工业杂志,2017,48(5):716
GENG ZP,JIANG YY,LI YD,et al.Determination of valsartan particle size by laser light scattering method[J]. Chin J Pharm, 2017,48(5):716
