本研究拟在无定形固体分散体和纳米混悬剂研究基础上构建新型的纳米晶固体分散体系，用于口服传递难溶性药物。采用固态“诱导结晶法”制备纳米晶型固体分散体并控制稳定态纳米晶粒径在20 nm~100 nm范围内，载药量高达50%~80%。通过测定体系界面能、混合能、结晶能及高分子载体与药物相互作用，从自由能角度研究该体系的稳定化机制，提出该体系的热力学判据。在此基础上，研究该体系的体内外相关性，评价其口服传递的有效性,并定量阐明肠道转运及吸收机制。该类型固体分散体能在特有胃肠道环境中还原而成纳米晶，并由载体聚合物稳定，不仅具有无定形固体分散体的有效性，而且规避了无定形固体分散体载药量低、稳定性差等问题；不仅继承了纳米混悬剂的高分散性和高载药量，而且解决了纳米混悬剂稳定性差、后处理难等问题。纳米晶型固体分散体的研究意义重大，将为难溶性药物口服传递和实现广泛工业化应用提供新的思路。

A new type nanocrystalline solid dispersion was established to orally deliver the poorly water-soluble drugs based on amorphous solid dispersion and nanosuspension. The "induced crystallization" method in solid state was used to prepare nanocrystalline solid dispersion, and stable nanocrystalline was obtained with particle size between 20 nm~100 nm, meanwhile, the drug loading was improved to 50%~80%. The stabilization mechanism of the system was established based on free energy analysis by study the mixing energy, interfacial energy, the crystallization energy and the interaction of the polymer and drug, and further the thermodynamic criterion was put forward. In addition, in vitro-in vivo correlation were studied to evaluate the efficiency of nanocrystalline solid dispersion and the oral transport and absorption mechanism in intestinal tract were explained. The nanocrystalline solid dispersion can change to nanocrystals stabilized by polymers in the gastrointestinal tract, not only have the property of amorphous solid dispersion, but also avoided the low drug loading and poor stability of it; not only have high dispersion and drug loading as nanosuspension, but also overcome the problems of poor stability and post-processing procedure. The research on nanocrystalline solid dispersion is meaningful, and would provide a new guidance for oral delivery of the poorly water-soluble drugs and the widely application and industrialization of the new solid dispersion.