伊贝沙坦脉冲微丸的制备方法

目的：考察伊贝沙坦脉冲控释微丸的制备工艺。方法：采用流化床工艺,将伊贝沙坦原料黏附在空白丸芯上,制成含药微丸;以低取代羟丙基纤维素为包溶胀层材料,乙基纤维素水分散体为包控释层材料,采用同样的工艺包溶胀层和控释层,并通过正交试验优选最佳工艺条件。按最佳包衣工艺操作,以低取代羟丙基纤维素、吐温-80、乙基纤维素水分散体和葵二酸二丁酯为包衣材料,以释药时滞及时滞后的突释药量为指标,优选最佳处方。结果：最佳工艺条件为：上药、包溶胀层、包控释层工艺中使用的风量分别为20、30、40 m3.h-1;进风温度分别为45、50、50℃;喷雾压力均为0.2 MPa;喷液速度分别为8、9、9.gs-1。4种包衣材料在微丸中所占的最佳质量百分比分别为25%、1%、25%和0.5%,制得的脉冲控释微丸的平均时滞约为7小时,时滞后2小时突释量均大于70%。结论：在该工艺条件下制备的伊贝沙坦脉冲控释微丸的体外释放能够达到脉冲控释效果,制备工艺简单、可控。

Preparation Process of Irbesartan Pulsatile Release Pellets

Objective：To investigate the preparation process of irbesartan pulsatile release pellets.Methods：The irbesartan pellets prepared by fluid-bed technique were coated in fluid-bed with low-substituted hydroxypropyl cellulose（L-HPC） as the inner swelled layer and ethyl cellulose aqueous dispersion as the outer controlled layer,and the process was optimized by orthogonal test.L-HPC,Tween-80,ethyl cellulose aqueous dispersion and dibutyl sebacate were selected for coating materials,and the formulation was optimized by using lag time and sudden release rate two hours after the lag time as two indexes.Results：The optimal process,including drug loading process,swelling layer coating process and controlled release coating process,were as follows：the air volumes were 20,30,40 m3 ·h-1,respectively,the inlet air temperatures were 45,50,50 ℃,respectively,the spray pressures were all 0.2 MPa,and the spray speeds were 8,9,9 g ·s-1,respectively.The optimal proportions of four kinds of coating materials in the pellets were 25%,1%,25% and 0.5%,respectively.The average lag-time of the pulsatile release pellets prepared by adopting the optimal formulation was about 7 hours and the sudden release rate two hours after the lag time exceeded 70%.Conclusion：The irbesartan pulsatile release pellets can meet the requirements of pulsatile release preparation in vitro,and the preparation process is both convenient and well-controlled.