索拉非尼固体分散体的制备及性质研究

The preparation and characterization of sorafenib solid dispersion

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。

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 physical state and dissolution of SFN in SD were hardly changed during the six months accelerated test.The cmaxof SD group was 1.8times that of powder group,relative bioavailability was 175%.Conclusion The physical stability of self-preparing solid dispersions is good,the dissolution and oral absorption are improved by solid dispersion.