文献类型：期刊文献

中文题名：Continuous synthesis of dolutegravir sodium crystals using liquid-gas heterogeneous microreactor

作者：Wei Luo[1];Fen Liu[1];Yaohao Guo[1];Junjie Qiu[1];Jinrui Yan[1];Shuangliang Zhao[1,2];Bo Bao[1]

机构：[1]State Key Laboratory of Chemical Engineering and School of Chemical Engineering,East China University of Science and Technology,Shanghai 200237,China;[2]Guangxi Key Laboratory of Petrochemical Resource Processing and Process Intensification Technology and School of Chemistry and Chemical Engineering,Guangxi University,Nanning 530004,China

年份：2023

卷号：34

期号：3

起止页码：302

中文期刊名：Chinese Chemical Letters

外文期刊名：中国化学快报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2023_2024】；PubMed;

基金：supported by the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality(No.19ZR1472200);National Natural Science Foundation of China(No.22178072)。

语种：英文

中文关键词：Microreactor continuous crystallization;Dolutegravir sodium;Reaction kinetics;Mixing mechanism;Crystal morphology;Process operation

摘要：In this work, a liquid-gas heterogeneous microreactor was developed for investigating continuous crystallization of dolutegravir sodium(DTG), as well as revealing reaction kinetics and mixing mechanism with 3-min data acquisition. The reaction kinetics models were established by visually recording the concentration variation of reactants over time in the microchannel via adding pH-sensitive fluorescent dye. The mixing intensification mechanism of liquid-gas flow was quantified through the fluorescent signal to indicate mixing process, demonstrating an outstanding mixing performance with a mixing time less than 0.1 s. Compared with batch crystallization, continuous synthesis of dolutegravir sodium using liquid-gas heterogenous microreactor optimizes crystal distribution size, and successfully modifies the crystal morphology in needle-like habit instead of rod-like habit. The microreactor continuous crystallization can run for 5 h without crystal blockage and achieve D90 of DTG less than 30 μm. This work provides a feasible approach for continuously synthesizing dolutegravir sodium, and can optimize the existing pharmaceutical crystallization.