Crystallization-Based Approach To Continuous Manufacturing: A Case Study of Acetaminophen Production

This study demonstrates a crystallization-based approach to designing and optimizing a fully continuous manufacturing process for acetaminophen (AcAP). By focusing on crystallization conditions, we developed an efficient process encompassing reaction, cooling crystallization, filtration, drying, and packaging. The reaction involved the acetylation of 4-aminophenol (4-AP) using a plug flow reactor (PFR), and the resulting mixture was subjected to cooling crystallization. The yield of AcAP was improved by controlling the pH using sodium hydroxide during crystallization. The obtained AcAP slurry was processed using a filtration, drying, and packaging system, and continuous manufacturing was successfully achieved for 5 h. This case study highlights the effectiveness of crystallization-based process design for the continuous manufacturing of fine chemicals, including pharmaceuticals and agrochemicals, offering a scalable and efficient strategy for industrial implementation.

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Journal
Organic Process Research & Development
Published
2026-01-13
DOI
https://doi.org/10.1021/acs.oprd.5c00332
Primary Topic
Innovative Microfluidic and Catalytic Techniques Innovation
Type
article
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Crystallization-Based Approach To Continuous Manufacturing: A Case Study of Acetaminophen Production

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Organic Process Research & Development
Innovative Microfluidic and Catalytic Techniques Innovation
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Crystallization-Based Approach To Continuous Manufacturing: A Case Study of Acetaminophen Production

Akira Yada, Tetsuya Yamamoto, Hidekazu Sano, Kwihwan Kobayashi, Aiichiro Nagaki, Koichiro Masuda, Ikuo Saito
article en

Abstract

This study demonstrates a crystallization-based approach to designing and optimizing a fully continuous manufacturing process for acetaminophen (AcAP). By focusing on crystallization conditions, we developed an efficient process encompassing reaction, cooling crystallization, filtration, drying, and packaging. The reaction involved the acetylation of 4-aminophenol (4-AP) using a plug flow reactor (PFR), and the resulting mixture was subjected to cooling crystallization. The yield of AcAP was improved by controlling the pH using sodium hydroxide during crystallization. The obtained AcAP slurry was processed using a filtration, drying, and packaging system, and continuous manufacturing was successfully achieved for 5 h. This case study highlights the effectiveness of crystallization-based process design for the continuous manufacturing of fine chemicals, including pharmaceuticals and agrochemicals, offering a scalable and efficient strategy for industrial implementation.

Organic Process Research & DevelopmentVol. 30(2)
Hokkaido University (JP), National Institute of Advanced Industrial Science and Technology (JP)
Industry, innovation and infrastructure
Openalex Percentile: Top 89%
Innovative Microfluidic and Catalytic Techniques Innovation
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