超临界CO_2流体技术制备纳豆激酶肠溶微丸的初探

Study on Enteric Coated Preparation of Nattokinase Using Supercritical CO_2 Fluid Technique

以异丁烯酸-丙烯酸乙酯共聚物Eudragit(L100-55为包衣材料,利用超临界CO2流体技术制备纳豆激酶口服肠溶包衣微丸,考察包衣效果,为纳豆激酶口服制剂的研究和开发提供实验依据。采用正交表考察各种因素对试验结果的影响;并按药典规定考察微丸在不同pH释放介质中的药物活性及释放行为。结果显示最适反应条件为:包衣材料和载药微丸质量比为1∶2,反应压力和温度分别为20 MPa、35℃,增塑剂柠檬酸三乙酯及助溶剂乙醇均为10%(V/m),抗粘剂滑石粉虽对包衣反应稍有影响,但能显著改善微丸粘连问题。体外实验结果表明所制备的最佳状态肠溶微丸在人工胃酸(pH1.2)环境中2 h仅释放9.7%,并能保持近90%的活性状态;在pH6.8的模拟肠液释放介质中2 h内快速释放达75%。以超临界CO2流体技术制备的纳豆激酶口服肠溶包衣微丸,在人工胃酸环境中几乎不释药,可避免胃酸环境对纳豆激酶活性的破坏;在pH6.8的类肠液环境中药物释放快速而完全,有利于纳豆激酶在肠道中的吸收。

To prepare enteric coated Nattokinase preparation ior oral administration via supercritical CO2 fluid technique, and to provide the experimental basis of Nattokinase oral preparation. The encapsulated pellets were prepared through supercritical CO2 fluid technique with the Eudragit^R L100-55 as coating material. The effects factors were studied by orthogonal test. The enzymic activity and releasing behavior of enteric coated pellets were determined at different pH value mediums according to the meth od of Chinese Pharmacopeia. The experiments showed that the optimum conditions were as follows： the ratio of coating material and pill, the pressure and the temperature were 1：2, 20 MPa and 35℃, successively both plasticizer triethyl citrate and auxiliary solvent ethanol were 10%（V/m）. The test in vitro showed that the drug was released only 9. 7% in the simulated gastric fluid （pill. 2） and the relative activity was remained nearly 90% in 2 h. But the releasing percentage reached 75% in 2 h, when the simulated intestinal fluid （pH6.8） was used. The Nattokinase was not released in the simulated gas tric fluid, which suggested that the Nattokinase enteric coated pellets protected drug the from being degraded by gastric acid. However, the drug was released quickly and completely from coated pellets in the simulated intestinal fluid,thus the Nattokinase can be absorbed easily in interstinal tract.