Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism  

作　　者：Abi Maharjan Hongyu Sun Zeying Cao Ke Li Jinping Liu Jun Liu Tiqiao Xiao Guanyun Peng Junqiu Ji Peter York Balmukunda Regmi Xianzhen Yin Jiwen Zhang Li Wu 

机构地区：[1]Center for Drug Delivery System,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation,Ministry of Education,Yantai University,Yantai 264005,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China [5]Shanghai Synchrotron Radiation Facility/Zhangjiang Lab,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201204,China [6]Hefei Lifeon Medication Group,Hefei 230088,China [7]Center for MOST and Image Fusion Analysis,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201210,China [8]Maharajgung Medical Campus,Institute of Medicine,Tribhuvan University,Kathmandu 44606,Nepal

出　　处：《Acta Pharmaceutica Sinica B》2022年第5期2568-2577,共10页药学学报（英文版）

基　　金：the National Nature Science Foundation of China (Nos.81803446,81803441 and 81773645);Key Program for International Science and Technology Cooperation Projects of China (2020YFE0201700);the Youth Innovation Promotion Association of CAS (2018323)。

摘　　要：Defining and visualizing the three-dimensional(3 D) 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 3 D 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). In situ formed 3 D structures at different in vitro 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 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via 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 observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.

关 键 词：Bilayer osmotic pump tablet Synchrotron radiation micro-computed tomography Three-dimensional microstructure Release kinetics Void formation Peripheral“roadways” Push-pull model Subterranean river model 

分 类 号：R943[医药卫生—药剂学]