摘要
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 ofimproving the solubility of the model drug. Methods Alcohol and simulated gastric fluid (SGF) wereused to dissolve cisapride and HPMC in order to make the model drug dispersed homogeneously in thecarrier. The HPMC-cisapride solid dispersion was then obtained by conventional solvent evaporationmethod. 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 soliddispersion was measured with water, SGF and simulated intestinal fluid (SIF) . The in vitro drugreleases of the sustained release tablet prepared with pure cisapride or HPMC-cisapride soliddispersion were investigated with water and SGF as media, respectively. Results No diffraction peakswere found by X-ray diffraction in the HPMC-cisapride solid dispersion (4:1), indicating that thedrug existed in an amorphous form at that drug-carrier ratio. Compared with the pure drug, thesolubilities of HPMC-cisapride solid dispersion are increased by 239.4% in SGF, 132.6% in water, and117.9% in SIF. According to the in vitro drug release, the sustained release tablet prepared withHPMC-cisapride solid dispersion had a faster drug release than did that prepared with pure drug. Thein vitro drug release profiles were found to comply with Higuchi's rule. Conclusion The in vitrodrug release of the sustained release tablet made by HPMC-cisapride solid dispersion is improvedowing to the increased drug solubility.
目的 以羟丙基甲基纤维素 (HPMC E5LV)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 2 39 4%、1 32 6 %和 1 1 7 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?
基金
Trans centuryTrainingProgramFoundationfortheTalentsbytheStateEducationCommission(2 0 0 10 3 )
