盐酸二甲双胍胃滞留缓释片的制备与质量考察

目的以卡波姆、羟丙基甲基纤维素、十八醇、碳酸氢钠等为辅料制备盐酸二甲双胍胃滞留缓释片,并考察其漂浮和释药特性。方法采用正交设计法,以漂浮性能为考察指标进行处方筛选,并用粉末干法直接压片;以人工胃液（1 000 mL）作为溶出介质,采用转篮法测定释放度,转速为150 r/min,温度为（37.0±0.5）℃;用高效液相色谱法测定含量,测定波长为233 nm;同时与市售普通片的体外溶出数据进行比较,并将体外释放数据用多种曲线方程进行拟合,分析拟合结果。结果研制的盐酸二甲双胍胃滞留缓释片起浮时间小于30 s,持续漂浮时间大于8h,具有良好的漂浮和缓释性能;该滞留片经Peppas方程拟合后释放参数n=0.5309,0.45〈n〈0.89,表明该药物体外释放属于骨架溶蚀与药物扩散协同作用。结论研制的盐酸二甲双胍胃滞留缓释片具有可在胃里漂浮及缓释效果,延长了胃部滞留时间,减轻了药物引起的刺激,并且质量可控。

Preparation and Quality Investigation of Metformin Hydrochloride Gastroretentive Sustained-Release Tablets

Objective To prepare Metformin Hydrochloride Gastroretentive Sustained-Released Tablets by using carbopol,hydroxypropylmethylcellose,octadecanol,sodium bicarbonate and other accessories and to investigate its behavior of floating and release characteristics.Methods By orthogonal design,the floating ability was used as index to screen the optimized formulation.The sustained-release tablets were prepared by direct powder compared to tablets technique.The dissolution was measured in artificial gastric juice（1 000 mL） as medium,the rotational speed was 150 r/min,the temperature was（37.0±0.5） ℃and the content was measured by HPLC at 233 nm.The dissolution of the sustained-release tablets was compared with common tablets and was fitted with several curves,also,the results of curve fitting were analyzed.Results The sustained-release tablets began to float in 30 s and floating time was over 8 h,which had good behavior of floating and release characteristics.Via Ritger-Peppas equation simulation,n=0.530 9,0.45 n 0.89,so,the drug release character was the synergistic effect of mixed erosion and drug diffusion.Conclusion The developed sustained-release tablets have the floating and sustained-release effects in stomach,extend the gastroretentive time and reduce irritation to stomach with better controllable quality.