磺丁基醚-β-环糊精的增溶机制及在难溶性药物制剂中的应用  

Solubilization Mechanism of Sulfobutylether-β-cyclodextrin and Its Application in Pharmaceutical Preparations for Poorly Soluble Drugs

作　　者：胡裕迪 赵雁[1] 陶涛[1] 

机构地区：[1]中国医药工业研究总院药物制剂国家工程研究中心,上海201203

出　　处：《中国医药工业杂志》2018年第3期292-300,共9页Chinese Journal of Pharmaceuticals

基　　金：国家科技重大专项--新辅料关键技术研究及产业化生产(2017ZX09201005-006)

摘　　要：磺丁基醚-β-环糊精(SBE-β-CD)是多阴离子的β-环糊精衍生物,分子呈圆台形状,圆台内部疏水,外部连接亲水性磺丁基醚取代基,圆台内部和侧链的烷基醚部分能够较好地容纳疏水性药物分子,具有增加药物溶解度、提高药物稳定性等功能和安全性良好的优点。自注射用伏立康唑上市以来,目前FDA已批准了9种使用SBE-β-CD增溶的注射剂产品,推动了对SBE-β-CD性质、分析方法、安全性及应用的研究。本文综述了SBE-β-CD对药物的增溶机制,包括包合作用、聚集作用及过饱和稳定作用,包合物制备过程在处方工艺上应关注的影响因素,包合物质量评价方法及SBE-β-CD在难溶性药物制剂尤其是注射剂中的应用。Sulfobutylether-β-cyclodextrin （SBE-β-CD）, a polyanionic β-cyclodextrin derivative, is donut- shaped with a hydrophobic interior and a hydrophilic exterior. The lipophilic molecules readily fit into the lipophilic center or interact with the alkyl ether section of the SBE side chains to form water-soluble drug-cyclodextrin complex. SBE-β- CD is safe when administered parenterally and exhibits the advantages of enhancing drug solubility and stability. Since the Vfend for injection was launched, FDA has approved 9 kinds of injection utilizing SBE-β-CD as a solubilizer. Therefore, there are extensive reviews and research papers on the solubilization properties, safety profiles, analytical methods and applications of SBE-β-CD. This paper summarizes the solubilization mechanism of SBE-[3-CD, including the formation of host-guest inclusion complexes, self-assembled aggregates in aqueous solutions and stabilization of supersaturated drug solutions. The components of formulation and parameters of preparation process which will influence solubilization efficiency have also been elucidated. Multiple analytical methods and applications of SBE-β-CD in pharmaceutical preparations especially injection for poorly soluble drugs are briefly summarized. In conclusion, SBE-β-CD will be practical and prospective in phannaceutics because of its beneficial properties and functionalities.

关 键 词：磺丁基醚-Β-环糊精 难溶性药物 增溶机制 注射剂 应用 综述 

分 类 号：Q539[生物学—生物化学]