李荣敏;何鸿玲;马志敏;潘怀耿;张晓婷;罗丹冬;
LI Rongmin;HE Hongling;MA Zhimin;PAN Huaigeng;ZHANG Xiaoting;LUO Dandong;Guangzhou Zengcheng Traditional Chinese Medicine Hospital;School of Chinese Medicine,Guangzhou University of Chinese Medicine;Asset and Laboratory Management Office,Guangzhou University of Chinese Medicine;The First Affiliated Hospital of Guangzhou University of Chinese Medicine;

• 1:广州市增城区中医医院
• 2:广州中医药大学中药学院
• 3:广州中医药大学资产与实验室管理处
• 4:广州中医药大学第一附属医院

摘要(Abstract)：

目的采用热熔挤出技术制备恩杂鲁胺三元固体分散体,以提高恩杂鲁胺的体外溶出度和稳定性。方法通过表观溶解度和溶出度试验,以醋酸羟丙甲纤维素琥珀酸酯(HPMCAS-H)为辅料,聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)、β-环糊精(β-CD),交联羧甲基纤维素钠(CCMC-Na)作为联合辅料,考察恩杂鲁胺三元固体分散体的溶出及物理稳定性。采用X射线粉末衍射(XRPD)、傅里叶红外光谱(FT-IR)和差示扫描量热法(DSC)对固体分散体进行体外表征,并考察了样品1年内的稳定性。结果与恩杂鲁胺-HPMCAS-H二元固体分散体相比,加入Soluplus、β-CD和CCMC-Na的作为第三组分的三元固体分散体可以进一步改善恩杂鲁胺的溶解性能,放置1年后三元固体分散体具有更高的物理稳定性。结论 Soluplus、β-CD和CCMC-Na三元组分的加入,可以提高恩杂鲁胺固体分散体的溶解性能和物理稳定性。
OBJECTIVE To improve the in vitro dissolution and stability of enzalutamide bulk drug by using hot-melt extrusion technology to prepare enzalutamide ternary solid dispersion METHODS Through apparent solubility and dissolution test, using hypromellose acetate succinate(HPMCAS-H) as the excipient, polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(Soluplus), β-Cyclodextrin(β-CD) and croscarmellose sodium(CCMC-Na) were used as another excipients to investigate the dissolution and physical stability of enzalutamide ternary solid dispersion. X-ray powder diffraction(XRPD), Fourier infrared spectroscopy(FT-IR) and differential scanning calorimetry(DSC) were used to characterize the solid dispersion in vitro. Also the stability of the sample was investigated after one year. RESULTS Compared with enzalutamide-HPMCAS-H binary solid dispersion, adding Soluplus, β-CD and CCMC-Na as the third component could further improve the solubility of enzalutamide, XRPD results showed that the ternary solid dispersion had higher physical stability than the binary solid dispersion after one year. CONCLUSION The addition of Soluplus, β-CD and CCMC-Na can improve the solubility and physical stability of enzalutamide solid dispersion.

关键词(KeyWords)： 热熔挤出;恩杂鲁胺;三元固体分散体;溶出度;物理稳定性
hot melt extrusion;enzalutamide;ternary solid dispersions;dissolution;physical stability

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 李荣敏;何鸿玲;马志敏;潘怀耿;张晓婷;罗丹冬;
LI Rongmin;HE Hongling;MA Zhimin;PAN Huaigeng;ZHANG Xiaoting;LUO Dandong;Guangzhou Zengcheng Traditional Chinese Medicine Hospital;School of Chinese Medicine,Guangzhou University of Chinese Medicine;Asset and Laboratory Management Office,Guangzhou University of Chinese Medicine;The First Affiliated Hospital of Guangzhou University of Chinese Medicine;

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