【作者】 郑昕； 杨睿； 唐星； 郑梁元；

【Author】 ZHENG Xin, YANG Rui, TANG Xing*, ZHENG liang-yuan (School of Pharmacy ,Shenyang Pharmaceutical University ,Shenyang 110016 ,China)

【机构】 沈阳药科大学药学院；

【摘要】 本研究采用热熔挤出工艺制备尼莫地平固体分散物,增加其溶解度和溶出速度。利用溶解度参数和流变学数据为指标筛选药物的合适载体,利用差热分析,X-射线粉末衍射,扫描电镜和红外光谱鉴别药物在载体中的状态,并进行体外溶出度研究,并采用beagle犬为实验动物进行生物利用度的研究。经溶解度参数的计算和流变学数据的考察初步筛选结果以HPMC、Eudragit EPO和S630为药物的载体,挤出物经物理化学方法确证后证实以Eudragit EPO和PVP/VA为药物载体情况下药物是以固态溶液的形式存在于固体分散体中,而HPMC的体系则仅仅是以无定形的状态分散于载体之中,溶出度实验表明利用热熔挤出方法制备的固体分散体中药物的释放速率均高于相应比例的物理混合物和原料药,生物利用度实验也证明了同样的结果。为热熔挤出技术在制药行业的深入研究和成熟应用作出了创新性的工作和有益的探索。更多还原

【Abstract】 The objective of the study was to characterize the physical and rheological properties of drug and selected polymers to assess their suitability for use in the hot-melt extrusion (HME) process as a means to improve solubility by manufacturing either solid dispersion or solid solution. The evaluation of the properties of the dispersions was performed using solubility parameters calculation, solubility measurements, dissolution studies, IR, DSC, SEM and XRPD. The results of experiments indicated that nimodipine were in the solid solution in the PVP/VA and Eudragit EPO systems, while amorphous state in the HPMC system. The solid dispersions of nimodipine with three formulations markedly enhanced drug dissolution compared to the pure drug and the physical mixturse. The enhancement of dissolution rate was influenced by the polymer drug ratio. The mean bioavailability of nimodipine was comparable after administration of the Eudragit? EPO solid dispersion and Nimotop?, but the HPMC and PVP/VA dispersions exhibited much lower bioavailability. However, the AUC0–12 h values of all three solid dispersions were significantly higher than physical mixtures with the same carriers and nimodipine powder.更多还原