新型茶碱口服结肠靶向给药系统的体内动力学

In vivo evaluation of a novel oral coating film tablet for the colon-specific drug delivery

目的研究以时间为释药开关的结肠靶向给药系统。方法以非pH依赖型聚丙烯酸树脂Eu dragit NE 3 0D为膜材 ,制备茶碱薄膜衣片 ;用HPLC法进行体内血药浓度分析 ;以γ 闪烁照相研究该制剂体内胃肠道的转运情况。结果本制剂与参比制剂主要药代动力学参数分别为 :tlag( 8 67± 1 0 4 )h、( 0 67± 1 1 5 )h ;Cmax( 5 2 5± 1 2 1 )mg/L、( 4 0 9± 1 2 5 )mg/L ;AUC0 2 6 ( 2 7 5 0±7 2 0 )mg·h/L、( 3 9 0 4± 1 0 4 3 )mg·h/L ;体内γ 闪烁照相研究表明 ,体外 6 5h释放的制剂口服8 0h后到达升结肠处开始释药 ,且体内释药与体外释药有一定的相关性。

Objective To evaluate a novel oral time-dependent colon-specific drug delivery in vivo. Methods The tablet cores containing theophylline as the model drug and carboxylmethyl starch sodium(CMS-Na) as the swelling agent were coated by the aqueous polymeric dispersions of Eudragit  NE 30D, which contains saccharose as the channel agent. The concentration of the theophylline in the plasma was quantified by HPLC. In addition, the movement of the dosage forms through the gastrointestinal tract was investigated by the γ-scintigraphic technology.Results The main pharmacokinetic parameters of these coating film tablets and reference tablets are as follows: t lag(8.67±1.04)h and (0.67±1.15)h;C max (5.25± 1.21)mg/L and (4.09±1.25)mg/L;AUC 0-26(27.50±7.20)mg·h/L and (39.04±10.43)mg·h/L,respectively. The γ-scintigraphic study shows that the in vitro 6.5 h release dosage form starts to disintegrate at the ascending colon after 8.0 h orally.Furthermore, the in vivo lag times correlats with the in vitro lag times to a certain extent.Conclusion The coating film tablets are potentially useful for the oral colon-specific drug delivery.