美托洛尔酒石酸盐胃内滞留漂浮型控释片的制备及药代动力学研究

DEVELOPMENT AND PHARMACOKINETIC STUDY OF ME TOPROLOL TARTRATE CONTROLLED-RELEASE TABLETE REMAINING-FLOATING IN STOMACH

本文根据水动力学平衡药物控释系统的设计原理制备了美托洛尔胃内滞留漂浮型控释片剂(简称M-HBS)。实验表明,本品的体外溶出符合一级动力学过程(K′r=0.1651 h^(-1));贮存期为两年;人体胃内γ-闪烁照相结果表明,本品在胃内滞留时间(5～6 h)明显比普通片剂(1.0～1.5 h)长;体内动力学过程符合表观一级吸收与一级消除的单室模型;ⅳ美托洛尔体内为双室模型;体内数据经NONLIN计算机程序处理,求得各项参数:Ka=0.1944 h^(-1),K=0.1867 h^(-1),Vd=2.813,t_(max)=5.247 h,C_(max)=125.1 ng/ml。本品的体内外数据具有显著的相关性(P<0.01)。

An oral controlled-release system (M-HBS) of metoprolol was developed based on the hydrodynamically balanced controlled drug delivery system. It was found that the in vitro release characteristics showed basically firstorder kinetics(K_r~'= 0.1651 h^(-1)); a tentative two-year expiration date on M-HBS was established; the γ-scintiphotographic study after oral ingestion showed that MHBS was retained in human stomach for longer time (5～6 h) than the conventional metoprolol tablet (1～1.5 h). The blood concentration-time course of M-HBS was demonstrated to fit a one-compartment model with apparent first order absorption and first order elimination. The parameters were calculated using a NONLIN computer program with the values of Ka, K, Vd, t_(max), c_(max), being 0.1944 h^(-1), 0.1867 h^(-1), 2.813, 5.247 h, 125.1 ng/ml, respectively. Moreover, the fraction of the close absorbed from M-HBS in vivo well correlated with dissolution rate in vitro.