Optimization of Metoprolol Tartrate Timing-release Pellets Based on Response Surface Methodology

OBJECTIVE To prepare metoprolol tartrate timing-release pellets. METHODS According to the swelling-blasting principal, the fluidized-bed spray technology was used to prepare metoprolol tartrate timing-release pellets with crosslinked carboxymethyl cellulose as the swelling layer material and ethyl cellulose as controlled release layer material. With the lag time and drug release rate as independent variables, the formulation was optimized by response surface methodology with Box-Behnken design. RESULTS The material and thickness of the swelling layers, the amount of pore forming agents and the thickness of the controlled release layer had significant influence on the lag time and the drug release rate of the pellets. According to the optimal formulation of pellets, the in vitro lag time was 4 h and more than 85% of the drugs were released from the pellets within 2 h. CONCLUSION The metoprolol tartrate loaded timing-release pellets prepared by the optimized prescription of response surface achieve the expected timing-drug release purpose.