索拉非尼固体分散体的制备及性质研究

目的制备索拉非尼（sorafenib,SFN）/介孔硅的固体分散体,并进行体内外性质研究。方法利用溶剂挥发法制备固体分散体,以溶出度为指标筛选药物和介孔硅比例;采用差示扫描量热法（DSC）和粉末X射线衍射（XRD）技术,考察药物存在状态及物理稳定性;通过电镜观察样品形貌;以大鼠为实验动物,以自制SFN粉末为对照,对固体分散体进行体内药动学研究。结果原料药为结晶态,溶出度〈10%;随着介孔硅的比例增大,固体分散体的溶出度增加,当SFN与介孔硅的比例为1∶5时,SFN以非晶态存在,溶出度〉90%,在6个月的加速实验中,药物存在状态和溶出度未见明显改变。固体分散体组的cmax是SFN粉末组的1.8倍...

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Bibliographic Details
Published in药学实践杂志 Vol. 34; no. 4; pp. 320 - 323
Main Author 单兴杰 闫占宽 于超峰 李传筠
Format Journal Article
LanguageChinese
Published 江苏恒瑞医药股份有限公司,江苏连云港,222000 2016
Subjects
介孔硅
固体分散体
溶出度
生物利用度
稳定性
索拉非尼
索拉非尼
mesoporous silica
sorafenib
solid dispersion
bioavailability
稳定性
dissolution
固体分散体
生物利用度
溶出度
stability
介孔硅
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Summary:目的制备索拉非尼（sorafenib,SFN）/介孔硅的固体分散体,并进行体内外性质研究。方法利用溶剂挥发法制备固体分散体,以溶出度为指标筛选药物和介孔硅比例;采用差示扫描量热法（DSC）和粉末X射线衍射（XRD）技术,考察药物存在状态及物理稳定性;通过电镜观察样品形貌;以大鼠为实验动物,以自制SFN粉末为对照,对固体分散体进行体内药动学研究。结果原料药为结晶态,溶出度〈10%;随着介孔硅的比例增大,固体分散体的溶出度增加,当SFN与介孔硅的比例为1∶5时,SFN以非晶态存在,溶出度〉90%,在6个月的加速实验中,药物存在状态和溶出度未见明显改变。固体分散体组的cmax是SFN粉末组的1.8倍,相对生物利用度为175%。结论 SFN/介孔硅固体分散体物理稳定性良好,能提高SFN的溶出度,改善其口服吸收效果。
Bibliography:31-1685/R
SHAN Xingjie, YAN Zhankuan, YU Chaofeng, LI Chuanjun （Jiang Su Heng Rui Medicine Co. , Ltd. , Lianyungang 222047, China）
sorafenib; mesoporous silica; solid dispersion; dissolution; stability; bioavailability
Objective To prepare sorafenib（SFN）/mesoporous silica solid dispersion（SD）and investigate characteristics in vitro and in vivo.Methods The SD was prepared by solvent evaporation method;the optimal ratio of SFN to mesoporous silica was determined by examining the dissolution of formula,the drug state and physical stability of SD were examined by DSC and XRD;the surface morphology was characterized by electron microscope;the pharmacokinetics of SD was studied for the solid dispersion which compared with SFN powders in vivo study using rats.Results SFN raw drug was crystalline and its dissolution was〈10%;the dissolution of SD increased with an increase in amount of mesoporous silica;when the ratio of SFN to mesoporous silica was 1∶5,drug in SD was non-crystalline state and the dissolution was〉90%.The
ISSN:1006-0111
DOI:10.3969/j.issn.1006-0111.2016.04.009