Maharjan Abi, Sun Hongyu, Cao Zeying, Li Ke, Liu Jinping, Liu Jun, Xiao Tiqiao, Peng Guanyun, Ji Junqiu, York Peter, Regmi Balmukunda, Yin Xianzhen, Zhang Jiwen, Wu Li
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China.
Acta Pharm Sin B. 2022 May;12(5):2568-2577. doi: 10.1016/j.apsb.2021.11.008. Epub 2021 Nov 13.
Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). formed 3D structures at different drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.
定义和可视化药物的三维(3D)结构为阐明药物递送系统的现象行为和潜在机制提供了一种新的重要工具。对于大多数固体3D结构而言,从复杂结构剂型(如双层渗透泵片)中释放药物的机制尚未得到广泛研究。在本研究中,对双层渗透泵片在溶解过程中以及在干燥固态下溶解后的情况进行了检查,并通过同步辐射显微计算机断层扫描(SR-μCT)进行了可视化。对在不同药物释放状态下形成的3D结构进行了全面表征。在干燥片剂样品的半透膜包衣下方,观察到NaCl晶体从推动层向药物层的独特移动模式。不同溶解时间的3D结构表明,双层渗透泵片中的推动热潮指向周边的“通道”。通常,在片剂样品药物溶解过程中,推动层中可分为渗透前沿、浸润区域和休眠区域的不同区域。根据观察到的3D微观结构,定义了一种药物释放机制的“地下河模型”来解释药物释放机制。