依折麦布片的制备及体内外评价

Preparation and in vitro-in vivo evaluation of ezetimibe tablets

目的采用粉末直压技术制备依折麦布仿制片剂。方法以依折麦布自制片的崩解时间及其与参比制剂的溶出曲线相似因子f2为主要考察指标,采用单因素实验筛选依折麦布片的最优处方;通过LC-MS/MS测定依折麦布片在比格犬体内的血药浓度计算药代动力学参数;通过测定依折麦布片对高胆固醇大鼠血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平的影响评价其药效作用。结果以最优处方制备的3批自制片与参比制剂体外溶出行为相似(f2>70),在比格犬内的药代动力学参数无显著差异(P>0.05),且对高胆固醇大鼠血清胆固醇水平的作用相当。结论本研究开发的依折麦布仿制片剂制备工艺简便,与参比制剂具有生物等效性,为依折麦布仿制药的开发提供参考。

ObjectiveTo prepare ezetimibe tablets by direct compression technology.MethodsBy comparison with the reference standard,the formulation of self-made ezetimibe tablets was optimized using the disintegration time and the release profile similarity factor f2 as the main indexes by the single factor experiments. The pharmacokinetic parameters of ezetimibe tablets in Beagle dog were determined by LC-MS/MS. The pharmacodynamic effects of ezetimibe tablets were evaluated by measuring serum total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels.ResultsThree batches of self-made ezetimibe tablets with the optimal formulation had similar in vitro dissolution behaviors as the reference preparations(f2>70). There was no significant difference in pharmacokinetic parameters in Beagle between the self-made ezetimibe tablets and the reference standard tablets,and the effect on the high serum cholesterol level was similar.ConclusionThe preparation process of the ezetimibe tablet developed in this study is simple,and the self-made tablet has bioequivalence with the reference standard,which provides a reference for the development of the ezetimibe generic drug.