The effect of initial precipitates on the induction period of l-ornithine-l-aspartate during semi-batch drowning out crystallization

Crystallization of l-ornithine-l-aspartate (LOLA) by drowning out was carried out using methanol as an antisolvent in a semi-batch crystallizer. Induction period for nucleation was obtained by a conductivity measurement to characterize the formation of LOLA crystals at different levels of supersaturation and various operating conditions (feed concentration, temperature and the presence of seeds with varying seed mass). It was found that generation and redissolution of initial precipitates occurred simultaneously in early feeding stage of aqueous LOLA solution into the antisolvent. At low feed concentration (≤0.5 mol LOLA/kg H₂O), the initial precipitates dissolved again and then supersaturation was generated. However, an enormous shower of nuclei during feeding was observed at high feed concentration and then supersaturation was generated with the presence of precipitates. These undissolved precipitates played as seeds which reduced the induction period in comparison with the low feed concentration case. The experimental results indicated that the LOLA crystals were formed by catastrophic secondary nucleation at high feed concentration. To confirm this nucleation phenomenon, the induction periods at various operating conditions were measured and compared with a cluster coagulation model which was a suitable nucleation model to interpret the catastrophic nucleation. The results showed a good agreement between the experimental data and the present model.