中心复合设计法优化依托贝特缓释胶囊处方

Optimization of the preparing formulation of etofibrate sustained release capsule based on central composite design and response surface methodology

目的:以体外释放度为指标,通过中心复合设计法优化依托贝特缓释胶囊处方。方法:采用包衣造粒机制备依托贝特丸芯,并用依托贝特、PEG 4000的丙酮溶液进行增溶层包衣,丙烯酸树脂EUD-RAGITRL30D水分散体包缓释衣层,装入00号胶囊制备缓释胶囊。采用中心复合设计对PEG 4000用量和缓释增重两个因素进行处方设计,测定体外释放度进行优化。结果:采用7.5%PEG 4000用量和5.7%缓释增重制备的缓释胶囊在24 h内释放85%以上,与参比制剂在同条件下的释放行为相似。结论:依优化处方制备的依托贝特缓释胶囊释放行为可控,优选处方制剂能在24 h持续缓慢释放。

Objective： To prepare etofibrate sustained release capsule and optimize its preparing formula- tion using central composite design and response surface method by evaluation of its in vitro drug release. Meth- ods： Etofibrate beads were prepared using centrifugal granulation equipment, and the first coating was performed with solution of etofibrate and acetone. The first coated beads were then coated with EUDRAGIT RL30D as sus- tained release layer. The prepared beads were filled into ＂00＂ type capsules. Central composite design was used to optimize the preparing formulation, and 3 batches of etofibrate sustained release capsules were prepared using the optimized preparing formulation. The preparing technique was optimized under testing of in vitro release. Results： The sustained release capsules were prepared using 7.5% PEG4000 and 5.7% gaining in weight for sustained re- lease coating, and the drug release amount was more than 85% in 24 h in selected dissolvent. The release behavior was similar to reference preparation. Conclusion： The capsules prepared by the optimized formulation have a con- trollable release behavior and can release sustainably and slowly in 24 h.