星点设计-效应面法优化尼可地尔胃漂浮缓释片制剂处方

Optimization of nicorandil gastric-floating sustained release tablets by central composite designresponse surface methodology

目的:应用星点设计-效应面法对尼可地尔胃漂浮缓释片进行处方优化。方法:采用粉末直接压片法,以制剂辅料中HPMC、十八醇和碳酸氢钠的用量为考察因素,以1,4,8 h的累积释放度和漂浮性能为评价指标,应用星点设计-效应面法优化制剂处方,并对胃漂浮缓释片释药机理做初步研究。结果:最佳制剂处方为:HPMC60 mg、十八醇40 mg、碳酸氢钠30 mg;经处方验证,体外累积释放度的预测值与实测值偏差<5%,起漂时间<5 min,续漂时间>8 h;经Ritger-Peppas方程拟合,n=0.535 7,提示该缓释片体外释放为非Fick扩散,具扩散与骨架溶蚀的双重机制。结论:应用星点设计-效应面法优选出了最佳制剂处方,按最佳制剂处方制备的尼可地尔胃漂浮缓释片具有良好的漂浮性能和缓释特性,制备方法简便。

OBJECTIVE To optimize formulation of nicorandil gastric-floating sustained release tablets by central composite design-response surface methodology （CCD-RSM）. METHODS Tablets containing nicorandil were prepared by direct powder compression method. In formulation designed with CCD-RSM, amounts of HPMC, octadecanol and NaHCO3 were taken as inde- pendent variables, and percentages of in vitro cumulative release at 1,4,8 h and floating performance were regarded as depend- ent variables. Release mechanism of drug from tablets was investigated. RESULTS Optimal formulation was HPMC 60 mg, otadeeanol 40 mg, NaHCO3 30 rag. Verified by prescription, bias of accumulative dissolution rate in vitro between predicted val- ue and observed value was less than 5%. Initial floating time was less than 5 rain and duration of floating was longer than 8 b. Ritger-Peppas equation fitting,n = 0. 535 7, hinting sustained release tablets in vitro released as non Fick diffusion with double mechanisms of drug＇s diffusion and matrix＇s dissolution. CONCLUSION CCD-RSM is successful in optimizing nicorandil gas- trio-floating sustained release tablets and gastric- floating sustained tablets have good floating and sustained release properties. This preparation method is simple.