文献类型：期刊文献

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

作者：Luo, Wei[1,2];Liu, Fen[1,2];Guo, Yaohao[1,2];Qiu, Junjie[1,2];Yan, Jinrui[1,2];Zhao, Shuangliang[1,2,3,4];Bao, Bo[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem Engn, Shanghai 200237, Peoples R China;[3]Guangxi Univ, Guangxi Key Lab Petrochem Resource Proc & Proc Int, Nanning 530004, Peoples R China;[4]Guangxi Univ, Sch Chem & Chem Engn, Nanning 530004, Peoples R China

年份：2023

卷号：34

期号：3

外文期刊名：CHINESE CHEMICAL LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000923084100001)】；

基金：This work is supported by the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipal- ity (No. 19ZR1472200) , and National Natural Science Foundation of China (No. 22178072) .

语种：英文

外文关键词：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 mu m. This work provides a feasible approach for continuously synthesizing dolutegravir sodium, and can optimize the existing pharmaceutical crystallization. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.