醋酸阿比特龙仿制制剂与参比制剂溶出曲线相似度研究

Similarity of Dissolution Profiles Between Generic and Reference Preparations of Abiraterone Acetate

目的建立醋酸阿比特龙片溶出度的测定方法,评价醋酸阿比特龙仿制制剂与参比制剂溶出曲线的相似性。方法采用桨法(转速50 r/min),测定醋酸阿比特龙片仿制制剂(B厂家、C厂家、D厂家,共9批)和参比制剂(A厂家,1批)样品在0.25%十二烷基硫酸钠(SDS)的水、0.25%SDS的pH 2.0盐酸溶液、0.25%SDS的pH 4.5磷酸盐缓冲液、0.25%SDS的pH 6.8磷酸盐缓冲液4种溶出介质中的溶出度。采用高效液相色谱法测定9批仿制制剂样品的溶出量,色谱柱为Agilent Eclipse Plus C_(18)柱(100 mm×4.6 mm,3.5μm),流动相为乙腈-水(80∶20,V/V),流速为1.0 mL/min,柱温为50℃,检测波长为254 nm,进样量为10μL;计算累积溶出量,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。结果与参比制剂比较,9批仿制制剂样品的体外溶出曲线均具有相似性,f_(2)均大于50。结论所建立的方法适用于醋酸阿比特龙片的溶出度测定,可为其质量标准提高和质量一致性评价提供参考。

Objective To establish a method for the determination of the dissolution of Abiraterone Acetate Tablets,and to evaluate the similarity of the dissolution profiles between generic and reference preparations of abiraterone acetate.Methods The paddle method(with a rotating speed of 50 r/min)was used to determine the dissolution profiles of generic preparation of Abiraterone Acetate Tablets(from manufacturers B,C,and D,nine batches)and reference preparation of Abiraterone Acetate Tablets(from manufacturer A,one batch)in four different dissolution media[water with 0.25%sodium dodecyl sulfate(SDS)and pH 2.0 hydrochloric acid solution with 0.25%SDS,pH 4.5 phosphate buffer with 0.25%SDS and pH 6.8 phosphate buffer with 0.25%SDS].High-performance liquid chromatography(HPLC)method was used to determine the dissolution of nine batches of generic preparations,the chromatographic column was Agilent Eclipse Plus C_(18) column(100 mm×4.6 mm,3.5μm),the mobile phase was acetonitrile-water(80∶20,V/V),the flow rate was 1.0 mL/min,the column temperature was 50℃,the detection wavelength was 254 nm,and the injection volume was 10μL.The cumulative dissolution rate was calculated,the dissolution profiles were drawn,and the similarity of the dissolution profiles was evaluated by the similarity factor(f_(2)).Results The in vitro dissolution profiles of the nine batches of generic preparation all showed similarity with the reference preparation,with f_(2)>50.Conclusion The established method is suitable for the determination of the dissolution of Acetate Abiraterone Tablets,which can provide a reference for the improvement of the quality standard and quality consistency evaluation of Acetate Abiraterone Tablets.