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% CaCl2(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.
国家自然科学基金(81872770，51205204); 河北省高等学校科学技术研究重点项目（ZD2017032）; 河北省大学生创新创业训练计划项目(201810082027)