基于效应面法优化酒石酸美托洛尔择时释药微丸处方

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

关键词:  效应面法  酒石酸美托洛尔  择时释药  溶胀-爆破原理  微丸

Key words:  response surface methodology  metoprolol tartrate  timing drug release  swelling-blasting principal  pellet

摘要:

目的 制备酒石酸美托洛尔择时释药微丸。方法 根据溶胀-爆破原理，以交联羧甲基纤维素钠为溶胀层材料、乙基纤维素为控释层材料，采用流化床底喷技术制备酒石酸美托洛尔择时释药微丸；采用Box-Behnken效应面法以时滞时间及时滞后药物释放度为考察指标优化其处方。结果 溶胀层、控释层的厚度及致孔剂的用量对微丸的时滞和释药速率均有显著影响。按最优处方制备的微丸，其体外释药时滞为4 h，时滞后2 h累积释药量>85%。结论 效应面优化处方所制备的酒石酸美托洛尔择时释药微丸达到预期的择时释药目的。

Abstract:

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.