Chen, Wen-ChingWen-ChingChenLee, Pin-DePin-DeLeeNi, Can-HongCan-HongNiChuang, Ya-HuiYa-HuiChuangLu, Guan-YuGuan-YuLuZhan, Jia-LinJia-LinZhanWong, Siu ChunSiu ChunWongYA-YU CHIANG2025-06-172025-06-172025-10-07https://www.scopus.com/record/display.uri?eid=2-s2.0-105003284099&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/730159The pharmaceutical industry is transitioning from batch to continuous manufacturing to reduce side product formation, enhance raw material recovery, and improve energy efficiency. However, inadequate purification technologies often force reversion to batch-based separation. This study demonstrates a fully integrated full-flow synthesis of acetylsalicylic acid (ASA) using a microreactor system coupled with a core-annular liquid–liquid phase separator. The microreactor ensures uniform residence time and complete mixing, enabling efficient ASA synthesis at room temperature. The custom-designed separator, employing a stretchable stainless-steel helix, achieves stable biphasic separation even under low interfacial tension, maintaining downstream ASA purity at 97.5 % and preventing clogging. A multifactorial analysis of variance revealed that full-flow processing at ambient temperature achieved higher ASA conversion (153.4 ± 10.4 mM) and reduced side product concentrations by 8.3 to 30.5 times compared to batch processes. These results underscore the system's potential to overcome key limitations in flow chemistry scale-up, providing a sustainable, high-performance alternative for pharmaceutical manufacturing.Acetylsalicylic acid synthesisANOVABiphasic liquid–liquid separationContinuous downstream processingContinuous manufacturingFlow chemistry[SDGs]SDG7[SDGs]SDG9journal article10.1016/j.seppur.2025.133107