左甲状腺素钠3D打印片在大鼠体内的药动学及体内外相关性

In vivo Pharmacokinetics and in vitro-in vivo Correlation of Levothyroxine Sodium 3D Printed Tablets in Rats

左旋甲状腺素钠(1)是治疗甲状腺功能减退症的首选药物,但治疗窗较窄。在临床使用中,1往往需要使用研磨、掰分等方法来切分剂量,可能会导致用药安全性降低。因此,本研究制备了13D打印分剂量片,探讨其与参比制剂的生物等效性,并建立了13D打印片的体内吸收与体外释药之间的相关性。结果表明,13D打印片与参比制剂具有生物等效性,且2种制剂的药动学过程均为一室模型。在3种溶出介质中,13D打印片和参比制剂的溶出曲线相似因子(f2)值均>50。A级体内外相关性拟合结果表明,13D打印片和参比制剂在3种溶出介质中的体外累积溶出率和体内吸收分数具有良好的相关性。该研究为3D打印片剂的体内外评价研究提供了参考。

Levothyroxine sodium(1)is the first choice for hypothyroidism treatment,but its therapeutic window is narrow.In clinical use,it is often necessary to use methods such as grinding and breaking to divide the dose,which may reduce the safety.Therefore,this study prepared 13D printing tablets,explored the bioequivalence between the 13D printed tablets and the reference preparations,and established the correlation between the in vivo absorption and in vitro drug dissolution of the 13D printed tablets.The results showed that 13D printed tablets and the reference preparations were bioequivalent,and both pharmacokinetic processes could be described by a one-compartment model.The similarity factor(f2)values of the dissolution curves of both preparations in three dissolution media were all above 50.The fitting result of Class A in vitro-in vivo correlation showed that the in vitro cumulative dissolution rate and the in vivo absorption fraction of the 13D printed tablets and the reference formulation measured in three dissolution media had a good correlation.This study provided a reference for the in vitro and in vivo evaluation research of 3D printed tablets.