盐酸拉贝洛尔片仿制制剂与参比制剂溶出曲线相似性研究  

Similarity of Dissolution Profiles Between the Imitative Preparation and Reference Preparation of Labetalol Hydrochloride Tablets

作　　者：郝丽娟 徐艳梅 苗会娟 王春霞 高燕霞 HAO Lijuan;XU Yanmei;MIAO Huijuan;WANG Chunxia;GAO Yanxia(Hebei Institute for Drug and Medical Device Inspection•NMPA Key Laboratory for Quality Control and Evaluation of Generic Drug,Shijiazhuang,Hebei,China 050227)

机构地区：[1]河北省药品医疗器械检验研究院•仿制药质量控制与评价重点实验室,河北石家庄050227

出　　处：《中国药业》2022年第24期51-55,共5页China Pharmaceuticals

基　　金：河北省中央引导地方科技发展资金项目[216Z4802G];河北省医学科学研究课题[20211193]。

摘　　要：目的 建立盐酸拉贝洛尔片溶出度的测定方法,评价盐酸拉贝洛尔片仿制制剂与参比制剂溶出曲线的相似性。方法 采用桨法,以高效液相色谱(HPLC)法测定制剂在4种溶出介质(pH1.2盐酸溶液、水、pH 4.0醋酸盐缓冲液和pH 6.8磷酸盐缓冲液)中的溶出量,色谱柱为Agilent Eclipse XDB-C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.1%磷酸溶液(25∶75,V/V),流速为1.0 mL/min,检测波长为230 nm,柱温为40℃,进样量为20μL;计算累积溶出度,绘制溶出曲线,并采用相似因子(f_(2))法评价溶出曲线的相似性。结果 盐酸拉贝洛尔在4种溶出介质中的质量浓度均在10.11-1 011.00μg/mL(r=0.999 7,0.999 8,0.999 6,0.999 9)范围内与峰面积线性关系良好;精密度、稳定性、重复性试验结果的RSD均小于1.5%。以参比制剂为对照,B厂仿制制剂样品以pH1.2盐酸溶液和pH 6.8磷酸盐缓冲液为溶出介质时所得溶出曲线与参比制剂具有相似性,C厂仿制制剂在4种溶出介质中均无此相似性。结论 本方法适用于测定盐酸拉贝洛尔片的溶出度,可为盐酸拉贝洛尔片仿制制剂的质量一致性评价提供参考。Objective To establish a method for the determination of the dissolution of Labetalol Hydrochloride Tablets,and to evaluate the similarity of the dissolution profiles between the imitative preparation and the reference preparation.Methods The dissolution of the preparation in four kinds of dissolution media(pH 1. 2 hydrochloric acid solution,water,pH 4. 0 acetate buffer and pH 6. 8 phosphate buffer) was determined by the high-performance liquid chromatography(HPLC) method with paddle method. The chromatographic column was Agilent Eclipse XDB-C_(18) column(250 mm × 4. 6 mm,5 μm),the mobile phase was acetonitrile-0. 1% phosphoric acid solution(25∶75,V/V),the flow rate was 1. 0 mL/min,the detection wavelength was 230 nm,the column temperature was 40 ℃,and the injection volume was 20 μL. The cumulative dissolution was calculated,the dissolution profile was drawn,and the similarity factor(f_(2)) method was used to evaluate the similarity of dissolution profiles.Results The mass concentration of labetalol hydrochloride in four kinds of dissolution media showed a good linear relationship with the peak area in the range of 10. 11-1 011. 00 μg/mL(r = 0. 999 7,0. 999 8,0. 999 6,0. 999 9). The RSDs of precision,stability and repeatability tests were less than 1. 5%. With the reference preparation as the control,the dissolution profile of the imitative preparation sample from manufacturer B with hydrochloric acid solution(pH 1. 2) and phosphate buffer(pH 6. 8) as the dissolution medium was similar to that of the reference preparation,while the imitative preparation sample from manufacturer C has no such similarity in the four kinds of dissolution media.Conclusion The method is suitable for the determination of the dissolution of Labetalol Hydrochloride Tablets,and can provide a reference for the quality consistency evaluation of the imitative preparation of Labetalol Hydrochloride Tablets.

关 键 词：盐酸拉贝洛尔片 溶出曲线 相似因子法 一致性评价 

分 类 号：R917[医药卫生—药物分析学] R972[医药卫生—药学]