盐酸地尔硫卓延迟缓释微丸的制备及处方优化

目的制备盐酸地尔硫卓延迟缓释微丸并对其处方进行优化。方法采用挤出滚圆法制备含药丸芯。采用流化床双层包衣技术以乙基纤维素为内层包衣材料,乙基纤维素与丙烯酸树脂的混合膜材为外层包衣材料制备延迟缓释微丸。以释放度为考察指标对其进行单因素考察,采用星点设计-效应面法优化处方,并对模型处方进行验证。结果单因素考察结果表明内层包衣增重、外层包衣增重以及外层包衣材料配比对释放度影响显著。通过所建立优化模型的效应面图可知,内层包衣增重X1=4.5%⁷.0%,外层包衣增重X2=7.0%7.0%,外层包衣增重X2=7.0%¹8.5%时所得的模型处方具有理想的释放时滞和释药速率。处方验证结果的f2相似因子为69.24>50,表明3批自制微丸的释药曲线与理论释药曲线具有良好的相似性。结论制备了具有理想释药时滞和释药速率的盐酸地尔硫卓延迟缓释微丸,所建数学模型具有良好的预测效果。

Preparation of diltiazem hydrochloride delayed-sustained release pellets and optimization of the formulation

Objective To prepare diltiazem hydrochloride delayed-sustained release pellets and optimize its formulation. Methods The core pellets, which contained the drug, were prepared by extrusion-spheronization. The pellets were double-layer coated with a fluidized bed coating equipment, with EC as the inner layer material and EC- Eudragit L100 as the outer layer material. Based on the single-factor study, the central composite design-response surface method was chosen to optimize the formula and the similarity of the release profiles was compared by similarity factor （f2）. Results The single-factor study indicated that the coating levels and the ratio of EC to Eudragit L 100 in the outer layer greatly affected the in vitro drug release. The model release profile could match the target release profile under the condition of inner layer coating levels （X1, 4.5% -- 7.0% ）, and outer layer coating levels 0（2, 7.0% -- 18.5%）. The value of f2 in the verification test was 69.24, which indicated that the release curve of the prepared formulation was similar to the target release profile. Conclusion The delayed-sustained release pellets of diltiazem hydrochloride are successfully prepared and the optimized model has a good predictive effect.