盐酸二甲双胍壳聚糖-海藻酸钠缓释微囊的制备及性能研究

Preparation and properties of metformin hydrochloride/chitosan/sodium alginate sustained-release microcapsules

目的制备盐酸二甲双胍壳聚糖-海藻酸钠缓释微囊并探索其性能。方法以壳聚糖和海藻酸钠为囊材,利用复凝聚法将盐酸二甲双胍微囊化。以微囊的药物包封率为制备工艺优化指标,用转篮法测定其体外溶出速率。结果通过正交实验得出微囊的最佳制备工艺条件为:壳聚糖浓度0.2%,成囊pH4.5,成囊温度45℃,搅拌速度200r/min。微囊的溶出释放性能实验显示,该载药微囊的累积释放速度远低于市售缓释片剂,在20h左右达到75%左右的最高累积释放值。结论以最佳制备工艺条件制备含药微囊重现性好、工艺稳定、吸水溶胀性好,体外溶出实验显示具有较好的缓释作用。

Objective To explore the technological process of preparing metformin hydrochloride/chitosan/sodium alginate sustained-release microcapsules,and investigate the properties of the microcapsules.Methods Metformin hydrochloride microcapsule was prepared by a coacervation process with natural polysaccharides chitosan and sodium alginate as the wall materials.The optimization criterion of the process was obtained by an orthogonal experimental design with drug encapsulation as reference standards.The drug dissolution rate was measured by the rotary basket method：the medicated microcapsules were put into a steel-wool basket and suspended in a volumetric flask filled with 1000ml PBS of pH 7.8-8.0,kept at 37℃with reciprocal shaking in speed of 100r/min.Results The optimal preparative condition for the microcapsules was as follows：the concentration of chitosan was 0.2% （w/v）,pH 4.5,the optimal temperature was 45℃,with shaking speed of 200r/min.The morphology of chitosan-sodium alginate microcapsules containing metformin hydrochloride was nearly uniform with an average diameter of ca.24.2μm.The encapsulation efficiency of medicated microcapsules was 48.2%and drug-loading rate was 9.6%.The medicated microcapsule absorbed water molecules quite slowly in the solution and swelled gradually up to the balance by 15hours.Compared with commercial sustained-release tablets,the release speed of prepared medicated microcapsule decreased significantly：for the former,the time to complete release was 3hours,while for the latter the time to 75%release was 20hours.Conclusions The medicated microcapsules prepared with optimal technological process have the advantages of good reproducibility and hydrating swelling property,and the technological process of preparation is stable.It has been shown that the prepared microcapsules possess excellent sustained-release performance.