沙库巴曲缬沙坦钠片体外溶出方法的建立及评价

Establishment and evaluation of the in vitro dissolution for sacubitril and valsartan tablet

目的 建立沙库巴曲缬沙坦钠片体外溶出测定方法,并对仿制制剂与参比制剂进行溶出曲线相似性的评价。方法 溶出度试验采用桨法,转速50 r·min^(-1);以0.1 mol·L^(-1)盐酸溶液、pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液、水各900mL为溶出介质;采用高效液相色谱法测定溶出量。结果 建立的体外溶出测定方法专属性、线性、准确度、重复性及精密度良好,供试品溶液室温放置48 h稳定;所有制剂样品在pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液及水中均能完全溶出,30min溶出量均>85%;3批仿制制剂与参比制剂溶出曲线的相似因子(f2)在0.1mol·L^(-1)盐酸溶液、pH4.5醋酸盐缓冲液、pH6.8磷酸盐缓冲液及水中分别为66~92、65~72、58~63及72~79。结论 体外不同生理pH溶出介质中,仿制制剂与参比制剂的溶出曲线相似因子(f2)均大于50,溶出曲线均相似,体外溶出行为一致,可为后续体内生物等效评价提供参考。

Objective To establish an in vitro dissolution method for sacubitril and valsartan tablets,and to evaluate the dissolution profile similarity of the generic and the reference preparations.Method Paddle method was adopted for the dissolution test and the agitation speed was set at 50 r·min^(-1);900 mL of 0.1 mol·L^(-1) hydrochloric acid solution,pH4.5 acetate buffer,pH6.8 phosphate buffer or purified water were used as the dissolution media;High performance liquid chromatography(HPLC)method was utilized to determine the dissolution amount.Results The in vitro dissolution method established had the good specificity,linearity,accuracy,repeatability and precision,and the test solution was stable at room temperature for 48 hours;All samples can totally be dissolved in pH4.5 acetate buffer,pH6.8 acetate buffer and purified water,the dissolution results of which were all above 85%in 30 min;The similarity factors(f2)of three batches of generic product against the reference preparation were between 66~92,65~72,58~63 and 72~79 in 0.1 mol·L^(-1) hydrochloric acid solution,pH4.5 acetate buffer,pH6.8 phosphate buffer or purified water,respectively.Conclusion The in vitro dissolution profiles of the generic product are similar to the reference preparation in different physiological pH media,similarity factor(f2)are all above 50.The consistent in vitro dissolution behaviors can provide a reference for the subsequent in vivo bioequivalence evaluation.