Continuous co-crystallization as a separation technology: The study of 1:2 co-crystals of phenazine-vanillin

The selective removal of vanillin in bioconversion by forming 1:2 co-crystals of phenazine-vanillin may serve as a new technology. Initial solvent screening experiments of vanillin, phenazine, and the co-crystals show that co-crystallization of phenazine and vanillin can be formed in toluene and, later, regenerated in acetone as Form α phenazine and vanillin solution. Co-crystallization is successfully carried out in both continuous and batch modes with no agitation and with stirring. However, it is found that the efficient heat transfer due to the instant drop of bulk solution temperature to 25 °C in continuous co-crystallization at 90 mL/min gives the advantages of a rapid nucleation rate, B⁰, of 2.8 × 10⁴ ± 4 × 10³ no/ls as determined by the mixed suspension, mixed product removal (MSMPR) formalism for the population balance, a wider and flatter size distribution of 18 wt % for particle sizes of >75 to >250 μm and about 12 wt % of >300 to >500 μm by sieve analysis, and a high yield of 51.2 ± 0.7 wt % in comparing with the ones of 34.9 ± 0.4 wt % from batch operation with no agitation and 57.7 ± 8.1 wt % from batch mode with stirring. The wider size distribution of particle sizes gives a better filterability of the wet cake and flowability of the dried co-crystals.