西沙必利-HPMC固体分散体对其体外药物释放的促进作用

西沙必利-HPMC固体分散体对其体外药物释放的促进作用

魏振平, 毛世瑞, 毕殿洲, 李勇*

1.北京大学公共卫生学院营养学系, 北京 100083;
2.沈阳药科大学药学院, 辽宁沈阳 110016;
3.天津大学化学工程与技术学院制药工程系, 天津 300072;

收稿日期:2004-06-12 修回日期:2004-11-10 出版日期:2004-12-15 发布日期:2004-12-15
通讯作者: 李勇*

Dissolution Improvement of Cisapride by Solid Dispersion with HPMC

WEI Zhen-ping, MAO Shi-rui, BI Dian-zhou, LI Yong*

1.Department of Nutrition, College of Public Health, Peking University, Beijng 100083, China;
2.College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110015, China;
3.Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China

Received:2004-06-12 Revised:2004-11-10 Online:2004-12-15 Published:2004-12-15
Contact: LI Yong*

摘要/Abstract

摘要： 目的以羟丙基甲基纤维素(HPMC-E5 LV)为载体材料制备HPMC-西沙必利固体分散体, 通过提高模型药物的溶解度来改善药物的体外释放. 方法分别用乙醇和人工胃液将药物和载体材料溶解, 使药物均匀分散在载体中, 减压干燥除去溶剂得到HPMC-西沙必利固体分散物; 用X射线粉末衍射法分别测定了纯载体材料、纯西沙必利、载体材料和西沙必利物理混合物以及载体材料和西沙必利固体分散体4:1的晶体衍射峰, 以确定是否有晶体存在; 分别考察纯西沙必利和HPMC-西沙必利固体分散体在水、人工胃液和人工肠液中的溶解度; 分别以纯西沙必利和载体材料和西沙必利固体分散体制备了西沙必利缓释片并考察了其在水和人工胃液中的药物释放. 结果当载体与药物的比例达到4:1时, X射线衍射实验表明药物的晶体峰已经消失, 形成无定型固体分散体; 与西沙必利原料药相比, 固体分散体中药物在人工胃液、水和人工肠液中的溶解度分别提高了239.4%、132.6% 和117.9%; 体外药物释放结果表明, 当以水和人工胃液为介质时,药物从固体分散体制备的缓释片中的释放速度要快于用纯原料药制备的缓释片中的释放速度, 体外释药规律可以用 Higuchi's 动力学方程描述. 结论以HPMC为载体材料与西沙必利制成固体分散体, 可以通过改善药物的溶解度来加快缓释制剂中药物的溶出速度.

关键词: 西沙必利, 西沙必利, 西沙必利, 羟丙基甲基纤维素E5LV, 羟丙基甲基纤维素E5LV, 羟丙基甲基纤维素E5LV, 固体分散体, 固体分散体, 固体分散体

Abstract: Aim To prepare a solid dispersion of cisapride with hydroxypropylmethyl cellulose (HPMC E5 LV) as carrier for the purpose of accelerating the in vitro drug release by means of improving the solubility of the model drug. Methods Alcohol and simulated gastric fluid (SGF) were used to dissolve cisapride and HPMC in order to make the model drug dispersed homogeneously in the carrier. The HPMC-cisapride solid dispersion was then obtained by conventional solvent evaporation method. Powder X-ray diffraction (XRD) was used to measure the diffraction peaks of pure carrier, pure cisapride, physical mixture of HPMC with cisapride (4:1), and HPMC-cisapride solid dispersion (4:1) to confirm the crystal existence. The solubility of pure drug and HPMC-cisapride solid dispersion was measured with water, SGF and simulated intestinal fluid (SIF). The in vitro drug releases of the sustained release tablet prepared with pure cisapride or HPMC-cisapride solid dispersion were investigated with water and SGF as media, respectively. Results No diffraction peaks were found by X-ray diffraction in the HPMC-cisapride solid dispersion (4:1), indicating that the drug existed in an amorphous form at that drug-carrier ratio. Compared with the pure drug, the solubilities of HPMC-cisapride solid dispersion are increased by 239.4% in SGF, 132.6% in water, and 117.9% in SIF. According to the in vitro drug release, the sustained release tablet prepared with HPMC-cisapride solid dispersion had a faster drug release than did that prepared with pure drug. The in vitro drug release profiles were found to comply with Higuchi's rule. Conclusion The in vitro drug release of the sustained release tablet made by HPMC-cisapride solid dispersion is improved owing to the increased drug solubility.

Key words: cisapride, cisapride, HPMC E5 LV, HPMC E5 LV, solid dispersion, solid dispersion

中图分类号:

R917.4

R943.41

Supporting: Foundation item: Trans-century Training Program Foundation for the Talents by the State Education Commission (200103).
^*Corresponding author. Tel.: 86-10-82801177; fax: 86-10-82801177

魏振平, 毛世瑞, 毕殿洲, 李勇*. 西沙必利-HPMC固体分散体对其体外药物释放的促进作用[J]. .

WEI Zhen-ping, MAO Shi-rui, BI Dian-zhou, LI Yong*. Dissolution Improvement of Cisapride by Solid Dispersion with HPMC[J]. .

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