索拉非尼固体分散体的制备及性质研究

单兴杰; 闫占宽; 于超峰; 李传筠

doi:10.3969/j.issn.1006-0111.2016.04.009

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索拉非尼固体分散体的制备及性质研究

单兴杰, 闫占宽, 于超峰, 李传筠

文章导航 > 药学实践与服务 > 2016 > 34(4): 320-323,342

单兴杰, 闫占宽, 于超峰, 李传筠. 索拉非尼固体分散体的制备及性质研究[J]. 药学实践与服务, 2016, 34(4): 320-323,342. doi: 10.3969/j.issn.1006-0111.2016.04.009

引用本文:

单兴杰, 闫占宽, 于超峰, 李传筠. 索拉非尼固体分散体的制备及性质研究[J]. 药学实践与服务, 2016, 34(4): 320-323,342. doi: 10.3969/j.issn.1006-0111.2016.04.009

SHAN Xingjie, YAN Zhankuan, YU Chaofeng, LI Chuanjun. The preparation and characterization of sorafenib solid dispersion[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(4): 320-323,342. doi: 10.3969/j.issn.1006-0111.2016.04.009

Citation:

SHAN Xingjie, YAN Zhankuan, YU Chaofeng, LI Chuanjun. The preparation and characterization of sorafenib solid dispersion[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(4): 320-323,342. doi: 10.3969/j.issn.1006-0111.2016.04.009

索拉非尼固体分散体的制备及性质研究

doi: 10.3969/j.issn.1006-0111.2016.04.009

江苏恒瑞医药股份有限公司, 江苏连云港 222000

The preparation and characterization of sorafenib solid dispersion

Jiang Su Heng Rui Medicine Co., Ltd., Lianyungang 222047, China

摘要: 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c_max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。
- 索拉非尼 /
- 介孔硅 /
- 固体分散体 /
- 溶出度 /
- 稳定性 /
- 生物利用度
Abstract: 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 c_max of SD group was 1.8 times 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.
- sorafenib /
- mesoporous silica /
- solid dispersion /
- dissolution /
- stability /
- bioavailability

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索拉非尼固体分散体的制备及性质研究

doi: 10.3969/j.issn.1006-0111.2016.04.009

江苏恒瑞医药股份有限公司, 江苏连云港 222000

收稿日期: 2015-09-09
修回日期: 2016-01-14

关键词:

索拉非尼 /

介孔硅 /

固体分散体 /

溶出度 /

稳定性 /

生物利用度

摘要: 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c_max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。