Diffusion is defined as general mechanism for drug release from advanced delivery systems, yet dynamic structure of dosage form intrinsically plays an unknown role. The synchrotron radiation X-ray micro-computed tomography (SR-μCT) three-dimensional (3D) imaging and in-depth analysis of 3D structures were applied to readily differentiate materials and accurately capture internal structure changes of multiple unit pellet system (MUPS) and the constituent pellets, visualizing internal 3D structure of a MUPS of theophylline tablets for their 3 levels hierarchy structures: pellets with rapid drug release characteristics, a protective cushion layer and a matrix layer. Drug release pathways were extracted from SR-μCT images and a 3D maze network was constructed using pore network analysis to quantify the internal structural evolution during drug release. In the initial stage of dissolution about 1 h, theophylline release from the MUPS is dominated by diffusion from the matrix layer, whilst the second phase of 23 h constant release kinetics is dominated by a 3D channel maze architecture with outlets/channels connecting pellets in the remains of the MUPS, which forms the 3D channel maze as pore networks. The random walking of the dissolved theophylline molecules retarded by the tortuous 3D channel maze which led to the observed controlled release profile as a whole. Based on SR-μCT investigations and 3D structure analysis, a new approach to control drug release via a 3D channel maze structure was discovered.

中文翻译：

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“3D 通道迷宫”控制多单位片剂的药物释放


扩散被定义为药物从高级递送系统释放的一般机制，但剂型的动态结构本质上起着未知的作用。同步辐射 X 射线显微计算机断层扫描 （SR-μCT） 三维 （3D） 成像和对 3D 结构的深入分析用于轻松区分材料并准确捕获多单位丸剂系统 （MUPS） 和组成丸剂的内部结构变化，可视化茶碱片剂 MUPS 的内部 3D 结构的 3 级层次结构：具有快速药物释放特性的丸剂， 保护垫层和矩阵层。从 SR-μCT 图像中提取药物释放途径，并使用孔隙网络分析构建 3D 迷宫网络，以量化药物释放过程中的内部结构演变。在溶解的初始阶段约 1 小时，茶碱从 MUPS 的释放以基质层的扩散为主，而 23 h 恒释动力学的第二阶段以 3D 通道迷宫结构为主，出口/通道连接 MUPS 残留物中的颗粒，形成 3D 通道迷宫作为孔隙网络。溶解的茶碱分子的随机行走被曲折的 3D 通道迷宫所阻碍，这导致了观察到的整体控释曲线。基于 SR-μCT 研究和 3D 结构分析，发现了一种通过 3D 通道迷宫结构控制药物释放的新方法。