硫酸特布他林脉冲控释微丸的制备

目的:制备硫酸特布他林脉冲控释微丸.方法:采用双层膜时控崩解原理制备脉冲控释微丸,使用水溶胀性材料为内包衣溶胀层,乙基纤维素水分散体为外包衣控释层.以释药时滞及时滞后的累积释药量为指标,溶胀层包衣液中SDS的浓度、溶胀层和控释层包衣增重为因素,采用L9 (34)正交试验优选最佳制备工艺条件.结果:药物通过控释层衣膜破裂而释放,内包衣层中SDS的加入量、溶胀层和控释层厚度对脉冲控释微丸的释药时滞和释药速率均具有显著性影响.按优选工艺制备的3批样品,溶胀层包衣液中SDS的浓度为0.05 mol/L、溶胀层包衣增重为16%、控释层包衣增重为18%,体外试验表明,平均所制备的脉冲控释微丸时滞为4.5 h,之后1.5 h累积释药均大于80%,达到了脉冲控释的要求.结论:制备的硫酸特布他林脉冲控释微丸,其药物的体外释放能够达到脉冲控释效果,本试验对硫酸特布他林脉冲控释系统的研究具有一定的参考价值.

Preparation of Turbutaline Sulphate Pulsatile Controlled-release Pellets

AIM:To prepare the turbutaline sulphate pulsatile controlled-release pellets (TB-PCRP). METHOD:The turbutaline sulphate pulsatile controlled-release drug delivery system were prepared by multile- layer coated technology with L-HPC as the inner coating swelling layer and ethylcellulose aqueous dispersion as outer coating controlled layer. The process was studied by orthogonal experiment design using orthogonal form L 9(3 4)with the lag time and the drug accumulated release as the evaluation quota to decide the best preparing condition,and the concentration of sodium dodecyl sulfate(SDS),the coating level of the swelling layer and the controlled layer as effecting factors. RESULT: The drug release is triggered while rupturing the membrane of controlled layer. The lag time and the accumulated release of turbutaline sulphate from the TB-PCRP are influenced obviously by the concentration of SDS,the coating level of the inner swelling layer and the outer controlled layer. Three batches of the optimum formulation were produced,and the release behavior determined \%in vitro\% of the TB-PCRP could meet all the requirements with a lag time of 4.5 h and more than 80% drug accumulated release within following 1.5 h under the simulated gastrointestinal pH conditions by using L-HPC and 0.05 mol/L SDS as the inner swelling layer with the 16%(w/w) coating level and the ethylcellulose aqueous dispersion as the outer controlled layer with the 18%(w/w) coating level. CONCLUSION: The results showed that the TB-PCRP prepared could meet all the requirements,and the methods of the optimization are useful for the turbutaline sulphate pulsatile controlled-release drug delivery system.