文献类型：期刊文献

英文题名：Modified rivaroxaban microparticles for solid state properties improvement based on drug-protein/polymer supramolecular interactions

作者：Chen, Ning[1];Di, Peiwen[1];Ning, Shangqi[1];Jiang, Wenjun[1];Jing, Qiufang[1];Ren, Guobin[1];Liu, Yan[1];Tang, Yun[1];Xu, Zhongyu[1];Liu, Guixia[1];Ren, Fuzheng[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2019

卷号：344

起止页码：819

外文期刊名：POWDER TECHNOLOGY

收录：;EI(收录号：20185206317071);WOS:【SCI-EXPANDED(收录号:WOS:000461262200079)】；

基金：The authors are grateful for finance support from the Shanghai Committee of Science and Technology (grant no. 14DZ1930802) and the National Natural Science Foundation of China (grant no. 21576080).

语种：英文

外文关键词：Bottom-up; Dissolution; Molecular docking; Rivaroxaban; Supramolecular interactions

摘要：To tailor the solid state properties of rivaroxaban (RXB), microparticles were prepared using an anti-solvent precipitation technique. A mixture of hydroxypropyl methylcellulose (HPMC) and bovine serum albumin (BSA) was used for modification of the crystallization process. The solid state properties of RXB microparticles were characterized by techniques including scanning electronic microscopy, differential scanning calorimetry and powder X-ray diffraction analysis. The microparticles were found to be small, ranging from 1 to 10 pm diameter with a good size distribution, and existed in a stable crystalline form. The nature of the drug-polymer/protein supramolecular interactions was explored by Fourier transform-infrared spectroscopy and fluorescence spectroscopy. Molecular docking was also conducted to validate the mechanism of the supramolecular interactions. Formation of the RXB-BSA complexes was mainly driven by van der Waals and hydrophobic interactions, which contributed to the particle size reduction. Hydrogen bonding between HPMC and RXB was responsible for polymorph control during crystallization. The results suggest that drug-polymer/protein supramolecular interactions play a vital role in modification of the solid state properties of poorly water soluble drugs. (C) 2018 Elsevier B.V. All rights reserved.