3D打印药物粉液粘结成型机制及微观结构对机械性能和释药行为的影响

3D打印高技术含量、交叉创新，融合多学科发展，在产品设计复杂度、产品个性化和按需制造方面具有极大的优势，3D打印技术将引领第四次工业革命。在制药行业，美国FDA于2015年批准全球第一款3D打印药品上市，但是由于高技术壁垒，仍有很多卡脖子问题尚未解决，特别是机制研究缺乏导致3D打印制剂成药性评价不足，目前尚无其他品种上市。本项目立足解决产业化的瓶颈问题，开展相关应用基础研究。以水溶性左乙拉西坦及难溶性药物替莫唑胺为模型药物，借助数学模型量化打印液流体学特征，结合不同喷射模式及不同属性喷射液，从微观角度阐明墨滴喷射机制及其影响因素；融合粉体学、物理药学、界面化学，从物态分子结构阐明粉液粘结机理，揭示腔室结构和微观构造对打印片剂机械性能和释药机制的影响；从计算机辅助设计、体外释放和体内释药三个层次，实现三维一体，进行个性化制剂体内外相关性研究，为我国3D打印制剂的创新研究及产业化奠定基础。

3D printing has high technology content, cross-innovation, and multi-disciplinary development. It has great advantages in product design complexity, product personalization, and on-demand manufacturing. 3D printing technology will lead the fourth industrial revolution. In the pharmaceutical industry, the US FDA approved the world ’s first 3D printed drug in 2015. However, due to high technical barriers, there are still many problems with jammed necks. In particular, the lack of mechanism research has led to insufficient evaluation of the drugability of 3D printed preparations. No other varieties are listed. This project is based on solving the bottleneck problem of industrialization and carrying out related application basic research. Using water-soluble levetiracetam and the insoluble drug temozolomide as model drugs, the mathematical model is used to quantify the fluid characteristics of the printing fluid, combined with different ejection patterns and different properties of ejection fluid, to clarify the droplet ejection mechanism and its influencing factors from a microscopic perspective Fusion of powder science, physical pharmacy, and interface chemistry to clarify the powder-liquid bonding mechanism from the physical molecular structure, reveal the influence of the cavity structure and microstructure on the mechanical properties and release mechanism of printed tablets; from computer-aided design, in vitro release With three levels of drug release in vivo, to achieve three-dimensional integration, research on the correlation between personalized preparations in vivo and in vitro, and lay the foundation for the innovative research and industrialization of 3D printing preparations in China.