摘要
本研究基于渗透泵原理,通过在双层渗透泵片芯外包隔离衣和控释衣,设计了具有理想释放时滞(Tlag)和释药速率(Rt)的盐酸地尔硫择时释放渗透泵控释片,并应用星点设计-效应面法对处方进行优化。以包衣膜中隔离衣增重(X1,mg)、控释衣膜中致孔剂的比例(X2,%)和控释衣膜增重(X3,mg)为自变量,以体外释放时滞Tlag(Y1)和平均释药速率Rt(Y2)为因变量,通过星点设计-效应面法优化处方。通过所建立优化模型的效应面图可知当X1=80～110 mg,致孔剂用量X2=14%～16%,控释衣增重X3=40～55 mg时所得的模型处方具有理想的释放时滞和释药速率。优化后的结果良好的解决了单因素考察所得处方中时滞时间与释放速率较难兼顾的问题。对模型处方进行f2相似因子验证,可得f2=79.29>50,因此所建数学模型具有良好的预测效果。
Objective： To prepare a new type of timed and controlled release osmotic pump of dihiazem hydrochloride. Methods： The system was optimized with the central composite design-response surface methodology, where the lag time （Tlog, Y1, h） and the release rate （Rt,Y2, mg· h^-1） of the dissolution profile were taken as dependent factor, while usage amount of subcoat weight gain （X1 , mg） , pore-former percentage （X2 , % ） and semi-permeable coat weight gain （X3 , mg） were taken as independent factors. Results： The optimal formulation showed a more prolonged lag time and an appropriate released rate than the one got from single factor investigation. The optimized model was verified with similarity factor （f2） between the dissolution profile of prepared formulation and the target dissolution profile. The model dissolution profile could match the target dissolution profile under the condition of subcoat weight gain （X1 ） among 80 - 110 mg, pore-former percentage （X2） among 14% - 16% , semi-permeable coat （X3 ） among 40- 55 mg. Conclusion： The timed and controlled release osmotic pump of dihiazem hydrochloride has been prepared; and the optimized model can predict results in the experiments.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2013年第9期1094-1099,共6页
Chinese Journal of New Drugs
基金
释药技术与药代动力学国家重点实验室课题(2012cb724000)
关键词
渗透泵
时滞
释药速率
星点设计
效应面法
盐酸地尔硫
osmotic pump
lag time
release rate
central composite design
response surface methodology
dihiazem hydrochloride
