共无定型药物系统的研究进展  

The development of co-amorphous drug systems

作　　者：姚静[1,2] 时念秋[2] 王杏林[2] 

机构地区：[1]河南大学药学院,河南开封475001 [2]天津药物研究院释药技术与药代动力学国家重点实验室,天津300193

出　　处：《药学学报》2013年第5期648-654,共7页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(973计划)资助项目(2012CB724002)

摘　　要：将两种水难溶性的晶态药物通过球磨、淬冷或低温研磨的方法制成共无定型药物系统,既能提高药物的稳定性及溶出速率,又能减少单一药物不良反应的发生,从而解决难溶性药物联合用药面临的诸多问题。通过差示扫描量热法(differential scanning calorimetry,DSC)、X射线粉末衍射法(X-ray powder diffraction,XRPD)、拉曼光谱(raman spectroscopy,RS)和傅里叶转换红外光谱(fourier transform infrared spectroscopy,FT-IR)等可以验证共无定型药物系统的形成情况和分子间相互作用。共无定型药物系统的稳定性由它的玻璃化转变温度(glass transition temperature,Tg)及分子间相互作用共同决定。依据Gordon-Taylor方程和Flory-Huggins方程可以分别推算理论Tg值和相互作用参数x,从而在分子水平上对共无定型药物系统进行理论分析。共无定型药物系统的出现为联合用药提供了新的思路。Converting two poorly water-soluble crystalline drugs to co-amorphous drug systems by ball milling, quench-cooling, or cryo-milling method can improve stability of the drug, enhance dissolution rates, and reduce adverse reactions of the single drug. Co-amorphous system has been used to solve problems of co-administration of medicines. Formation and intermolecular interactions of co-amorphous drug systems may be verified by differential scanning calorimetry （DSC）, X-ray powder diffraction （XRPD）, raman spectroscopy （RS） and fourier transform infrared spectroscopy （FT-IR）. Stability of co-amorphous drug systems is influenced by their glass transition temperature （Tg） and intermolecular interactions. The theoretical Tg values and the interaction parameter x are calculated by Gordon-Taylor equation and the Flory-Huggins equation, respectively. Thus, co-amorphous drug systems are analyzed theoretically at molecular level. Co-amorphous drug systems provide a new sight for the co-administration of medicines.

关 键 词：共无定型药物系统 分子间相互作用 Gordon-Taylor方程 Flory-Huggins方程 联合用药 

分 类 号：R943[医药卫生—药剂学]