硝酸异山梨酯缓释微丸处方及工艺优化

Study on the formulation and preparation of the sustained-release pellets of Isosorbide dinitrate

目的制备硝酸异山梨酯缓释微丸,优化处方及制备过程。方法采用粉末层积法和流化床喷雾法制备膜控缓释微丸,用单因素考察实验优化处方及工艺,采用HPLC法测定缓释微丸的累积释放度。结果确定以Eudragit RS30D和Eudragit RL30D混合分散体为包衣材料,Eudragit RS30D与Eudragit RL30D的比例是4∶1,包衣增重为5%,热处理温度、时间为40℃、24小时,抗静电剂、增塑剂分别占包衣聚合物量的0.5%、20%。在体外释放度实验中,微丸累积释放硝酸异山梨酯百分率,0.5小时为10.71%,2小时为45.80%,8小时90.79%,24小时为99.14%。结论体外释放度实验中,Eudragit RS30D与Eudragit RL30D的比例对微丸累积释放度的影响较大,随着包衣量增加,释放度略有降低。本制剂为膜控制剂。

OBJECTIVE To prepare the sustained-release pellets of isosorbide dinitrate and optimize formulation and preparation process. METHODS The sustained-release pellets were prepared by a powder layering with centrifugal granulation equipment and coating with fluid-bed spraying processor. The formulation and preparation were optimized by the simple factor investigation. HPLC was utilized to determine the accumulation dissolution of the sustained-release pellets. RESULTS The coating formula was composed of Eudragit RS 30D and Eudragit RL 30D with the best proportion of 4 ： 1 and coating level of 5 %. The curing temperature and time were 40℃ and 24hrs. The static electricity-proofing and plasticizers occupied 0.5 % and 20 % of polymerizer, respectively. The accumulation dissolution precentage in vitro of ISDN from the sustained-release pellets was 10.71% at 0.5h, 45.80% at 2h,90.79% at 8h, and 99.14% at 24h, respectively. CONCLUSIONS It indicated in the in vitro drug releasing study that the proportion of Eudragit RS 30D and Eudragit RL 30D had a significant effect on the accumulated drug releasing of the pellets while in contrast the weight gain of the coating had a little effect. The preparation studied in the paper is membrane-controlled releasing.