摘要
通过喷雾干燥方法制备载药量高达60%的恩杂鲁胺二元和三元固体分散体,以提高其溶出度。通过表观溶解度试验考察了4种辅料[聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)、聚丙烯酸树脂(Eudragit L100)、乙烯吡咯烷酮-乙酸乙烯酯共聚物(Kollidon VA64)和聚乙烯吡咯烷酮(PVP K30)]的增溶作用和抑晶效果,从中筛选合适的辅料;又加入表面活性剂(十二烷基二苯醚二磺酸钠盐和十二烷基硫酸钠)制备了三元固体分散体,并进行体外溶出度试验。采用X射线粉末衍射(XRPD)、扫描电镜(SEM)和差示扫描量热(DSC)分析对制备的固体分散体进行物相鉴别。结果表明,以Soluplus为辅料制备的二元无定形恩杂鲁胺固体分散体能显著提高药物的溶出速率和溶解度。三元固体分散体相较于二元固体分散体能进一步改善恩杂鲁胺的溶解性能,且对过饱和状态下的药物具有良好的抑晶作用。
Enzalutamide solid dispersions with a drug loading up to 60% were prepared by spray drying, in order to enhance the dissolution extent and rate of the poorly soluble drug, enzalutamide. The solubilization and crystallization inhibition effects of four polymers [polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus), methacrylic acid copolymers (Eudragit L100), vinylpyrrolidone-vinyl acetate copolymers (Kollidon VA64), polyvinylpyrrolidone (PVP K30)] were investigated by apparent solubility test. Based on the screening results, a surfactant [sodium lauryl diphenyl ether disulfonate (Dowfax 2A1) or sodium dodecyl sulfate (SDS)] was added to prepare ternary solid dispersions. Then, the in vitro dissolution of binary solid dispersions with different carriers and the above ternary solid dispersions were investigated in phosphate buffer containing 0.1% Tween-80. The physicochemical properties of the products were characterized by X-ray powder diffraction (XRPD) analysis, scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The results showed that enzalutamide existed in an amorphous state form in both binary and ternary solid dispersions prepared with Soluplus. It indicated that Soluplus could significantly improve the dissolution rate and extent of enzalutamide. Compared with the binary solid dispersions, the ternary solid dispersions could further improve the solubility of enzalutamide, and could maintain good crystallization inhibition effect in the supersaturated solution.
作者
饶秋红
丘振文
罗丹冬
李庆国
刘莺燕
RAO Qiuhong;QIU Zhenwen;LUO Dandong;LI qingguo;LIU Yingyan(The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405;School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006;Dangyang City People's Hospital in Hubei Province, Dangyang 444100)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2019年第3期315-319,324,共6页
Chinese Journal of Pharmaceuticals
关键词
恩杂鲁胺
喷雾干燥
三元固体分散体
表征
溶出度
enzalutamide
spray drying
ternary solid dispersion
characterization
dissolution
