Abstract: Encapsulated sustained-release doxycycline hydrochloride pellets (SRDP) were developed. SRDP was designed so that drug release was through a diffusion rate controlling membrane constituting the pellet coat and thus could be used to reduce the gastrointestinal injuries in human induced by doxycycline (DX). SRDP showed drug liberation pattern which was best described by zero-order kinetic equation with release constant being 20.5 mg/h; A tentative two-year expiration date on SRDP was established; The new dosage form was shown to be significantly less irritative to gastric mucosa than a commercially available conventional tablet (CCT,) (p<0.001), and no more irritating than a placebo. The blood concentration-time course was demonstrated to fit a classical one-compartment model with apparent zero order absorption and first order elimination. The parameters were calculated based on the individual and average serum level data using a NONLIN computer program with mean values of k_a, k, Vd, t_max C_max being 58.08mg/h, 0.032h^-1, 82.21L, 3.94 h and 2.30 μg/ml, respectively. Information derived from observed data in vivo and the pharmacokinetic analysis suggested that during the usual therapeutic dosage regimens of DX, SRDH was bioequivalent to CCT. Moreover, in vivo drug availability well correlated with in vitro values.