Novel Technique for Filtration Avoidance in Continuous Crystallization

Fouling and clogging of lines in both continuous crystallization and flow chemistry still present a challenge in designing continuous processes. This paper presents a proof of concept for a novel unit operation designed for purification and to eliminate the need for slurry handling in API manufacturing by utilizing a dynamic (falling) film-based solution layer crystallization technique called “filtration-avoidance”. Fenofibrate (with fenofibric acid as an impurity) and acetaminophen (with metacetamol as an impurity) in different solvents were tested as crystallization systems, and the final purities and yields are reported. Sixteen different combinations of materials and process parameters were investigated. The results show significant improvement in the purity of the main compounds and a high yield for the process, which indicates a potential industrial application for a filtration-free continuous separation process, e.g., final purity of 99.4% was achieved from the experiment with a solution of 98% fenofibrate and 2% fenofibric acid (impurity) in pure ethanol (at a flow rate of 15 mL/min and a column temperature of 0 °C).