Continuous-Flow Synthesis and Optimization of Aspirin as a Model Active Pharmaceutical Ingredient: Process Evaluation and Comparative Pharmaceutical Relevance

Abstract

Continuous-flow chemistry is an important process-intensification approach for active pharmaceutical
ingredient (API) synthesis because it provides precise control over residence time, temperature, pressure,
mixing, and reagent delivery. The present study aimed to develop and evaluate a continuous-flow synthesis
process for aspirin as a model API and compare its process relevance with conventional batch synthesis.
Aspirin was synthesized by acetylation of salicylic acid using acetic anhydride in the presence of an acid
catalyst under controlled flow conditions. The effects of residence time and temperature were evaluated,
and the product was assessed using chromatographic and spectroscopic techniques together with melting
point determination and yield calculation. The yield increased from 72% at 30 s and 80°C to 94% at 90 s
and 90°C. A further increase to 120 s and 100°C slightly reduced the yield to 91%, suggesting possible
impurity formation, hydrolysis, or product degradation under harsher conditions. The optimized condition
was therefore identified as 90 s residence time at 90°C. The study demonstrates that continuous-flow
synthesis can improve reaction efficiency, safety, reproducibility, and process control for aspirin synthesis.
The broader relevance of flow chemistry for selected APIs is also discussed