星点设计-效应面法优化盐酸罗沙替丁醋酸酯胃漂浮缓释片制剂处方

Formulation Optimization of Roxatidine Acetate Hydrochloride Gastric-floating Sustained Release Tablets by Central Composite Design-Response Surface Methodology

目的制备盐酸罗沙替丁醋酸酯(ROX)胃漂浮缓释片,并对其制剂处方进行优化。方法应用粉末直接压片法制备ROX胃漂浮缓释片,以处方中辅料用量为考察因素,以体外累积释药百分率与制剂漂浮性能为评价指标,通过星点设计-效应面法(CCD-RSM)优化制剂处方;考察缓释片的释药机制。结果优选的制剂处方为羟丙基甲基纤维素(HPMC)55 mg、十八醇100 mg、碳酸氢钠(NaHCO3)50 mg、乳糖118 mg、微粉硅胶2 mg;所得制剂起漂迅速,持续漂浮时间8 h;以Ritger-Peppas模型拟合体外释药曲线,n=0.668 1(提示非Fick扩散),初步表明药物释放机制以扩散与溶蚀方式并存。结论经CCD-RSM优化处方制得的ROX胃漂浮缓释片,缓释效果和漂浮性能良好。

Objective To optimize the formulation of roxatidine acetate hydrochloride(ROX) gastric-floating sustained release tablets by central composite design-response surface methodology(CCD-RSM). Methods Gastric-floating sustained release tablets were prepared by direct powder compression method.In formulation designed with CCD-RSM,amounts of excipients were taken as independent variables,percentages of in vitro cumulative release at each time point and floating performance were regarded as indexes.Releasing mechanism of tablets was investigated. Results Optimized formulation was HPMC 55 mg,octadecanol 100 mg,NaHCO3 50 mg,lactose 118 mg,and micro silica gel 2 mg.It floats quickly and lasts for 8 hours.The drug release process conforms to the Ritger-Peppas model, n=0.668 1, indicating non-Fick diffusion.The drug was released in a diffusion and dissolution co-existence manner. Conclusion The ROX gastric floating sustained-release tablet prepared by CCD-RSM optimized formulation has good sustained-release and floating properties.