文献类型：期刊文献

英文题名：Enhancement of solubility and dissolution rate of dipyridamole by salifying: Preparation, characterization, and theoretical calculation

作者：Yi, Dongxu[1];Dong, Yuhang[1];Yao, Yichen[1];Hong, Minghuang[1];Zhu, Bin[1];Ren, Guo-Bin[1];Qi, Ming-Hui[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Engn Res Ctr Pharmaceut Proc Chem, Lab Pharmaceut Crystal Engn & Technol,Minist Educ,, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2024

卷号：1296

外文期刊名：JOURNAL OF MOLECULAR STRUCTURE

收录：;EI(收录号：20234214903807);WOS:【SCI-EXPANDED(收录号:WOS:001098618600001)】；

基金：The work was supported by National Natural Science Foundation of China (No. 22078094) and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission).

语种：英文

外文关键词：Dipyridamole; Salt; Solubility; Fluorescence

摘要：Dipyridamole (DIP) is a medication utilized to treat cardiovascular diseases, belonging to the BCS II class of drugs with low solubility and high permeability. As the effectiveness of oral preparations is influenced by the solubility and dissolution rate of the active ingredients, this study developed eight salts for solid modification of DIP to overcome poor water solubility. These salts were characterized using single crystal X-ray diffraction, powder Xray diffraction and thermal analysis. Dipyridamole-oxalate (DIP-OLA) and dipyridamole-malonate (DIP-MNA) showed significant increase in apparent solubility and dissolution rate in buffer compared to DIP. The crystal structure analysis showed that the improved solubility is due to the change of the dipyridamole conjugate system and the molecular arrangement in the crystal after the introduction of counterions. It is noteworthy that the fluorescence emission of some salts in the solid state is significantly stronger than that of DIP. According to the crystal structure, the destruction of n-n stacking of DIP molecules after salification is the main mechanism of fluorescence enhancement, and Hirshfeld analysis and HOMO-LUMO analysis are also used to further explain the fluorescence changes.