文献类型：期刊文献

英文题名：Efficient Production of Inhalable Micro-Nanoparticles: Mechanism, Process Optimization, and Modular Continuous Micro-Crystallizer Design

作者：Wang, Yuan[1,2];Chu, Ding-Jun[4];Li, Jin-Liang[4];Xie, Xiao-Qiang[4];Ren, Guo-Bin[1,2,3];Qi, Ming-Hui[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Lab Pharmaceut Crystal Engn & Technol, Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[4]Aurisco Pharmaceut Co Ltd, Tiantai 317200, Zhejiang, Peoples R China

年份：2025

卷号：29

期号：5

起止页码：1264

外文期刊名：ORGANIC PROCESS RESEARCH & DEVELOPMENT

收录：;EI(收录号：20252118452163);WOS:【SCI-EXPANDED(收录号:WOS:001473249300001)】；

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

语种：英文

外文关键词：continuous crystallization; continuous coaxial mixingcrystallizer; crystal engineering; micro-nanoparticles

摘要：Batch production of micro-nanoparticles suffers from high energy consumption and low efficiency, and continuous crystallization is considered a promising solution. This study reported the design of a modular continuous coaxial mixing crystallizer (CCMC) system for the production of micro-nanoparticles of the pharmaceutical compound fluticasone propionate (FP), and the performance of the system was evaluated. Guided by experimentally determined thermodynamic and kinetic data of FP crystallization, computational fluid dynamics simulations were employed to optimize the crystallizer design, resulting in enhanced mixing efficiency occurring within 40 ms. Through a three-stage experimental protocol, the continuous crystallization process was optimized: (1) key process parameters were screened using factorial design; (2) the operational design space was mapped via response surface methodology; and (3) particle size control mechanisms were elucidated through analysis of mixing processes. Quantitative analysis identified the antisolvent-to-solution ratio as the dominant factor governing particle size distribution, attributed to its critical role in nucleation kinetics. The CCMC platform demonstrated robust and efficient operation for 25 min, delivering a single-run output equivalent to 990 doses of commercial formulation. Comparative studies revealed advantages over batch processing, including comparable powder crystallinity, improved crystal morphology, and narrower size distributions within a micro-nanometer range. The coaxial mixing crystallizer system exhibits excellence in flexibility, productivity, and material recovery.