壳聚糖-海藻酸钠载药微球制备工艺研究

为研究制备壳聚糖-海藻酸钠载药微球的新方法,研究采用D相乳化法,结合微乳及胶体制备技术,以硫酸小檗碱为模型药物,以药物包封率为评价指标,应用单因素试验考察了氯化钙溶液浓度、海藻酸钠溶液浓度、壳聚糖溶液浓度,以及初次凝胶时间对微球性能的影响。应用响应面法筛选优化了载药微球的制备工艺。结果表明,在微球制备及药物包封率的影响因素中,海藻酸钠溶液浓度、氯化钙溶液浓度对评价指标的影响最大,其次是壳聚糖溶液浓度和初次凝胶时间,筛选优化的载药微球生产工艺条件为海藻酸钠溶液浓度1.57%,氯化钙溶液浓度2.13%,壳聚糖溶液浓度0.86%,初次凝胶时间30.71min,该条件下制备微球的平均粒径为329nm,药物包封率94.09%。验证试验证实,本工艺可制备优良的硫酸小檗碱壳聚糖-海藻酸钠微球,且制备工艺简便,生产效率高,本技术为微球制剂的产业化生产奠定了一定基础。

Study on Preparation Process of Chitosan-Sodium alginate Drug-loaded Microspheres

In order to develop a new method for preparing chitosan-sodium alginate drug-loaded microspheres,the D-phase emulsification method,combined with microemulsion and colloid preparation method was used in this study.Single-factor tests were used to investigate the effects of calcium chloride concentration,sodium alginate concentration,chitosan concentration and gel-forming time on the performance of microcapsules taking berberine sulfate as a model drug,and the drug encapsulation efficiency as evaluation index.The preparation process of drug-loaded microspheres was optimized by response surface methodology.The results showed that among the factors of microsphere preparation,sodium alginate concentration and calcium chloride concentration had the greatest influence on the evaluation index,followed by chitosan concentration and gel-forming time of microspheres.The optimized drug-loaded microsphere preparation process was sodium alginate concentration of 1.57 %,calcium chloride concentration of 2.13%,chitosan concentration of 0.86% and gel-forming time of 30.71 min.The average particle diameter of the prepared microspheres was 329 nm,and the drug encapsulation efficiency was 94.09 %.The verification experiment confirmed that the application of the test process can prepare excellent berberine sulfate chitosan-sodium alginate microspheres,and the preparation process is simple and the production efficiency is high.The technology provided a basis for the industrial production of microsphere preparations.