盐酸二甲双胍pH敏感性水凝胶微球的制备

Preparation of metformin hydrochloride loaded pH-sensitive hydrogel microspheres

为减轻盐酸二甲双胍对胃的刺激,实现其在肠道内的释放,以盐酸二甲双胍为主药,壳聚糖、海藻酸钠为复合载体,筛选盐酸二甲双胍pH敏感性水凝胶微球的最佳处方及制备工艺,并对其pH敏感性及体外释药特性进行了考察。通过单因素试验及正交试验优化处方工艺,利用扫描电镜进行结构表征,紫外分光光度法测定载药量及包封率,转篮法研究释放度。结果表明,盐酸二甲双胍pH敏感性水凝胶微球的优选处方如下:壳聚糖与海藻酸钠的总浓度为2%(质量体积比),海藻酸钠与壳聚糖的质量比为1∶1,药物与海藻酸钠的质量比为2∶5,氯化钙的交联浓度为3.5%(质量体积比);盐酸二甲双胍pH敏感性水凝胶微球在人工胃液中6 h累积释放度小于4%,在人工肠液中6 h累积释放度最大可达96.4%。所制备的盐酸二甲双胍pH敏感性水凝胶微球处方工艺稳定可靠,水凝胶微球机械强度高,生物降解性和稳定性好,是一种新型结构的盐酸二甲双胍给药系统。

In order to avoid the irritation of metformin hydrochloride to the stomach and realize its release in the intestine,with metformin hydrochloride as the main drug and chitosan/sodium alginate as the composite support,the optimal formulation and preparation technology of metformin hydrochloride loaded pH-sensitive hydrogel microspheres were selected,and the pH-sensitivity and in vitro drug release characteristics were investigated.The formulation and process were optimized by single factor test and orthogonal test.The morphology was characterized by SEM.The entrapment efficiency and drug-loaded amount were determined by UV.The release degree was studied by rotating basket method.The results show that the optimized prescription is as following:chitosan and sodium alginate with a total concentration of 2%(mass-volume ratio),mass ratio of sodium alginate to chitosan=1∶1,mass ratio of drug to sodium alginate=2∶5,and 3.5%CaCl 2(mass-volume ratio).The cumulative release rate is less than 4%in artificial gastric juice within 6 h,and up to 96.4%in artificial intestinal juice within 6 h.The formulation and process are stable and reliable,and the hydrogel microspheres have high mechanical strength,good biodegradability and stability.So it is a new metformin hydrochloride delivery system.