ABSTRACT
Background The time rhythm of human body is associated with the occurrence and development of manydiseases. Kinds of diseases of particular onset biorhythm provided the room for the development ofchronopharmacological drug delivery systems.Aim In this work, the drug release and pharmacokinetics behavior of metoprolol tartrate (MT) pulsatile tabletdeveloped in our lab was investigated to figure out its feasibility of convenient drug taking to exert effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris.Methods The in vitro release behavior of MT pulsatile tablets was investigated by using basket method. Theappearance and morphology of MT pulsatile tablets during drug release was observed by naked eye and scanning electronic microscope, respectively. In vivo pharmacokinetics performance was studied in NewZealand rabbits.Results The lag time of MT pulsatile tablets was approximately 7 h in vitro, and a fast release was observedthereafter, with more than 90% releasing within 10 min. The pharmacokinetics study in rabbits demonstrateda perfect consistence in the absorption lag time of 7.04 ± 0.29 h in vivo. Compared with the marketedconventional tablet, the MT pulsatile tablet showed a bioequivalence in absorption extent with a relativebioavailability of 110.04%, but not in absorption rate.Conclusion The designed lag time of 7 hours enabled the MT pulsatile tablets to achieve effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris with a high attack rhythmaround 4:00-6:00 A.M by giving medicine conveniently around 22:00 P.M. the night before.