无定型药物单相固态分散体系的多核相关固体核磁共振研究

项目名称： 无定型药物单相固态分散体系的多核相关固体核磁共振研究

项目编号： No.21205129

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 分析化学

项目作者： 张海禄

作者单位： 中国科学院苏州纳米技术与纳米仿生研究所

项目金额： 25万元

中文摘要： 众多市售和在研固体药物难水溶的性质导致其生物利用度低，将药物分子以无定型形式分散于辅料中可以提高溶解度。单相分散体系期望被获得以获得高的溶解度并避免相分离导致的重结晶风险。本项目主要采用先进的多核相关固体核磁共振技术，包括1H-1H、1H-杂核二维相关CRAMPS技术，1H-14N、13C-14N多共振技术(TRAPDOR、S-RESIDOR、S-RESPDOR)，结合谱编辑和弛豫时间测量，研究药物/高分子辅料、药物/小分子辅料、药物/小分子/高分子辅料三类药物无定型单相分散体系中的分子间近邻关系、相互作用及药物多态性。研究结果有助于深入了解此类体系药物宏观性能与微观状态之间的关系，为无定型药物制剂的设计与开发提供基础支撑。

中文关键词： 无定型药物；固体分散物；固体核磁共振；分子间相互作用；二维相关谱

英文摘要： Many commercial oral drugs and drug candidates are poorly soluble, which leads to low oral bioavailability. The use of amorphous solid dispersion can improve the solubility for many drug molecules. Single phase is often a disirable state for drug delivery, as it generally offers the benefits of high solubility with the least risk of phase separation and recrystallization into less water-soluble crystalline phase. In this study, three kinds of amorphous solid dispersion, including drug/polymer, drug/small molecule excipient, and drug/small molecule/polymer, will be subjected to advanced solid state NMR analysis.1H-1H and 1H-X(X=13C,15N)2D CRAMPS correlation, 1H-14N and 13C-14N double resonace, as well as relaxation time measurement solid state NMR experiments will be used, which has the capability to reveal the intermolecular proximity and interaction in these dispersions, as well as the microscopic state of amorphous drugs in different conditions. The results of this study will greatly enhance our knowledge of the relationship between microscopic properities and macroscopic performance of amorphous drugs, and provide solid foundation towards further formulation design.

英文关键词： Amorphous drug；Solid dispersion；Solid state NMR；Intermolecular interaction；2D correlation spectrum