【作者】 周英辉；

【导师】 黄明智；

【作者基本信息】 北京化工大学 ， 应用化学， 2003， 硕士

【摘要】 本文通过对明胶/海藻酸钠聚合物交联网络的研究,确定了在制备微胶囊中应用的基材配比,并应用2%明胶和2%海藻酸钠混合溶液作为基材,以戊二醛和氯化钙水溶液作为交联剂,采用注射法制备了粒径分布在900μm左右的微胶囊。以明胶/海藻酸钠复合体系用作基材,对药物奥美拉唑(Omeprazole)进行微胶囊化研究,结果表明,明胶/海藻酸钠聚合物互穿网络制得的微胶囊具有pH敏感的特性:在模拟胃液酸性环境的介质中进行静态释放,微胶囊的溶胀和药物的的释放得到了很大程度的抑制;而在模拟肠液的接近中性的介质中,微胶囊的溶胀和药物的释放都较快,为突释型。实验结果表明,制备微胶囊时,交联时间的长短对药物的释放规律没有太大的影响,而主要影响微胶囊的溶胀速率、溶胀度及药物释放速率。交联时间长的,形成的微胶囊结构比较紧密,在同样的pH值介质中,药物的释放较缓。在所研究的交联时间中,交联时间为4h的微胶囊达到最大溶胀百分率的时间比较短,使溶胀对药物的释放影响最小。不同温度下的微胶囊具有不同的溶胀行为,在相同的pH值条件下,温度高,溶胀速度较快,溶胀度较大;温度低的介质中,溶胀速度较慢,溶胀度较小,温度高有利于药物的释放,而温度低则减缓药物的释放。在pH接近中性或弱碱性的条件下,微胶囊的溶胀程度较大,而酸性条件下溶胀程度相对小得多,pH对溶胀度的影响为控制此微胶囊药物释放的主要方法之一。应用Peppas经验方程对明胶/海藻酸钠体系制得的微胶囊进行释放规律的模拟,并确定了不同交联时间的微胶囊在不同 pH<WP=4>值的介质中释放的动力学参数,n、k及相关系数r等。在接近中性的条件下,药物的释放为non-Fickian的释放形式。应用Flory-Rehner方程,算得了不同交联时间下制备的微胶囊的交联分子量Mc,并得出,交联时间越长,明胶/海藻酸钠聚合物交联互穿网络的交联分子量越小,越不利于药物通过扩散过程释放到介质中。微胶囊的应用温度越高,算得的交联分子量Mc越大,此时芯材的释放越容易。明胶/海藻酸钠作为基材制备pH值敏感型微胶囊,应用于包埋药物奥美拉唑,对改善其生物利用度,提高药效有很大的应用价值。更多还原

【Abstract】 A new pH-sensitive material based on gelatin/sodium alginate interpenetrating polymer network (IPN) by the microencapsulated method was investigated. The mixture solution in which the concentration of gelatin/sodium alginate solution was both 2wt% was used to prepare the microcapsules. Through the approach of the cross-linking microcapsules in the solvent bath composed of glutaraldehyde and calcium chloride, the formed microcapsules had the well-defined sizes of about 900μm. A comparative study of pH-dependent release of Omeprazole was carried out with such microencapsulating system. The results indicated that the microcapsules deswelled in acidic medium and swelled in alkaline, and the drugs’ cumulative release had the similar principle.The cross-linking time had no great influence on the medicament release in the preparation process of microcapsules. However, it was tied up with swelling rate, swelling ratio of the microcapsules and release rate of the medicament therein. The long cross-linking time resulted in more compact structure of microcapsules and the low release rate of the medicament in the medium of same pH value. As for the cross-linking time investigated, the microcapsules of 4h cross-linking time exhibited a shorter time to reach the maximum swelling ratio and showed a minimum swelling influence on the medicament release. The microcapsules at different temperature exhibited different swelling behavior. At the medium with the same pH value, the higher the temperature was, the faster the swelling process exhibited, the greater the swelling ratio as well. All these indicated that the higher temperature was favorable to the medicament release. At a neutral <WP=6>or basic pH value solution, the microcapsule exhibited a greater swelling ratio, but the lower swelling ratio at an acid pH value, indicating that the influence of pH value on the swelling ratio of the microcapsules was a key factor for the control of medicament release.The release process of the microcapsules prepared by gelatin/sodium alginate was simulated using Peppas Equation. The release kinetics parameters of the microcapsules at different cross-linking time and different pH values were determined. In the neutral condition, the medicament release showed a non-Fickian form. The cross-linked molecular weights of the microcapsules at different cross-linking time were calculated via Flory-Rehner Equation. The results showed that the longer cross-linking time resulted in a lower cross-linked molecular weight of gelatin/sodium alginate IPN and was unfavorable to the medicament release into mediums. With the increasing of temperature, the cross-linked molecular weight increased which could make the release of medicament easier.It was concluded that the gelatin/sodium alginate as a kind of backing material possesses a great application merit for the preparation of pH-sensitive microcapsule for omeprazole.更多还原