【作者】 索绪斌； 邓英杰； 张涵； 江晓间； 王玉强；

【Author】 SUO Xu-bin1,2, DENG Ying-jie2, ZHANG Han3, JIANG Xiao-jian1, WANG Yu-qiang1 (1 Institute of New Drug Researching, School of Pharmacy, Jinan University, Guangzhou510632, China; 2 Departments of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 3 Shanghai University of TEM, Shanghai 201203, China )

【机构】 暨南大学药学院新药研究所； 沈阳药科大学药学院； 上海中医药大学；

【摘要】 目的月桂酰吲达帕胺是一个水难溶性的药物,将它制成脂质体凝胶剂后,考察该制剂中药物体外释放的影响因素。方法采取无膜释放模型,在智能溶出仪中进行研究,考察脂质体凝胶剂在释放面积分别为2.27cm2、1.54cm2及0.79cm2时药物的释放,同时研究脂质体凝胶中药物的释放和脂质体凝胶的溶蚀速度之间的关系。检测凝胶中释放出来的脂质体粒径和对药物的包封率,考察脂质体在制成凝胶剂前后,脂质体粒径和包封率的变化,探讨凝胶中释放出来的药物的存在形式。维持桨的高度,释放面积及温度不变,改变桨的搅拌速度,考察桨的搅拌速度对药物释放及脂质体凝胶溶蚀的影响。以Tris缓冲盐溶液、0.9%氯化钠溶液和10%小牛血清为脂质体凝胶中药物的释放介质,考察释放介质对药物从脂质体凝胶中释放的影响。结果月桂酰吲达帕胺从脂质体凝胶剂中的释放速度随着释放面积的增大而加快,并且药物的释放百分比和凝胶的溶蚀百分比之间存在着线性关系:y=0.9656x+0.7371,(r=0.995),说明脂质体凝胶的溶蚀决定着药物的释放。脂质体的粒径和包封率从凝胶中释放前后变化不大,说明药物是以脂质体的形式从凝胶中释放出来。药物的释放随着桨搅拌速度的增加而加快,药物的释放百分率和搅拌桨的角速度之间存在着线性关系:y=15.31+3.779,(r=0.999)。脂质体凝胶在10%的小牛血清中溶蚀最快,而在该释放介质中药物释放则最慢,脂质体凝胶剂在Tris缓冲盐溶液和0.9%氯化钠溶液中药物的释放及凝胶溶蚀速度基本相同。结论月桂酰吲达帕胺在脂质体凝胶中的释放主要受凝胶的溶蚀控制。药物主要以脂质体的形式从脂质体凝胶中释放出来,包封率和粒径变化不大。释放面积,桨的搅拌速度及释放介质均影响脂质体凝胶的溶蚀及药物的释放。更多还原

【Abstract】 OBJECTIVE Lauroyl-indapamide is a water-insoluble drug. After it has been made into its liposomal hydrogel dosage form, the release behaviors of lauroyl-indapamide from its liposomal hydrogel have been studied. METHODS The membrane-less model has been used to study the drug release from its liposomal hydrogel in the dissolution apparatus when their release areas were set at 2.27 cm2、1.54 cm2 and 0.79 cm2 respectively, and the correlation of the percentages of drug release and those of liposomal hydrogel dissolution has been studied. The sizes and entrapment efficiencies of liposomal lauroyl-indapamide have been detected to study the form that drug appeared in the dispersion media after it released from the liposomal hydrogel. The influences of the stirring speed of peddle on the drug release and liposomal hydrogel dissolution has also been studied while the release areas, peddle height and temperature were fixed in the experimental process. Tris buffer solution, 0.9% physiological saline and 10% calf serum have been used as the dispersion media to study the influences of dispersion medium on the drug release. RESULTS The released rate of lauroyl-indapamide from the liposomal hydrogel correspondingly increased with the release area, and the percentages of liposomal hydrogel dissolution and those of drug release showed a good linear correlation, the line is y = 0.9656 x + 0.7371, (r = 0.995), which suggests that the drug release was significantly dependent on the liposomal hydrogel dissolution. The sizes and drug entrapment efficiencies of liposomal lauroyl-indapamide showed little difference from the liposomes that before it made into the liposomal hydrogel, which suggests that drug was always released in its liposomal form. Drug release rate increased correspondingly with the stirring speed of peddles, and there exists a good linear correlation between the percentages of the hydrogel dissolution and those of drug release, and the line is y = 0.9656 x + 0.7371, (r = 0.995). Liposomal hydrogel dissolved faster with its drug release rate lower in the 10% calf serum, while the liposomal hydrogel dissolution rate and drug release rate were almost the same while used 10% calf serum and 0.9% physiological saline as the dispersion media. CONCLUSIONS Drug release from the liposomal hydrogel was significantly dependent on the dissolution of liposomal hydrogel. And the lauroyl-indapamide was always released in liposomes form, and the sizes and entrapment efficiencies of the liposomes changed little. Drug release rate was significantly influenced by release area, stirring speed of peddles and the sorts of dispersion mediums respectively.更多还原