微观结构对药物结晶固体分散体关键药剂学参数的影响机制研究

结晶固体分散体（CSD）是一种可提高难溶性药物口服生物利用度的新型固体制剂。微观结构作为CSD的物质基础是决定其物理稳定性、溶出行为等关键药剂学参数的根本因素，然而由于缺乏深入、系统的研究，微观结构的形成机制以及其对关键药剂学参数的影响因素尚无定论，因此目前无法对制剂进行科学设计和有效评估。. 本课题将以半结晶、三嵌段共聚物泊洛沙姆作为CSD的载体，首先建立一套基于结晶动力学和结晶机制的实验方法学，从分子层面系统地揭示CSD微观结构的形成机制；其次研究CSD微观结构对药剂学关键参数的影响，通过阐明微观结构形成的分子机制以及对其关键药剂学参数的影响因素，归纳出基于药物结晶机制和分子作用机理的、普适的制剂设计思路，并对关键药剂学参数进行有效预测。. 本项目将试图解决CSD在设计过程中缺乏理论依据和对关键药剂学参数难以预测的问题，为合理设计CSD提供理论和实验依据，对新药研发具有重要指导价值。

Crystalline solid dispersion (CSD) is a novel solid preparation which can improve the oral bioavailability of poorly water-soluble drugs. As the material basis of CSD, microstructure is the fundamental factor to determine the physical stability, dissolution behavior and other key pharmaceutical parameters. However, due to the lack of in-depth and systematic research, the formation mechanism of microstructure and its influencing factors on the key pharmaceutical parameters are still uncertain, so it is impossible to carry out scientific design and effective evaluation of the preparation at present.. In this project, poloxamer will be used as the carrier of CSD. Firstly, a set of experimental methodology based on crystallization kinetics and crystallization mechanism will be established to systematically reveal the formation mechanism of CSD microstructure from the molecular level. Secondly, the influence of CSD microstructure on the key pharmaceutical parameters will be studied. By clarifying the molecular mechanism of the formation of microstructure and the influencing factors of its key parameters of pharmacy, it will be concluded that Based on the mechanism of drug crystallization and molecular action, a general idea of drug preparation design was proposed, and the key pharmaceutical parameters were effectively predicted.. This project will try to solve the problem that CSD lacks theoretical basis and is difficult to predict the key pharmaceutical parameters in the design process, provide theoretical and experimental basis for the rational design of CSD, and have important guiding value for new drug research and development.