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

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.