Design and validation of batch crystallizer to study non-photochemical laser-induced nucleation

Abstract

Crystallization is an important process occurring in the nature, pharmaceutical, and food industries. It is one of many widely used unit operations for the separation and purification of chemicals industrially. Despite its far-reaching application in fine chemicals and active pharmaceutical ingredients production, the stochastic nature of nucleation makes it difficult to obtain crystals with reproducible properties like size, structure, purity, and polymorphic form. The accidental discovery of Non-Photochemical Laser-Induced Nucleation (NPLIN) in 1996 emerged as a novel technique to tame the crystallization process. Since the laser provided better spatiotemporal control over crystal properties in a solution, NPLIN gained abundant traction over the past decades in the vial and microfluidic scaled experiments.
On the contrary, this research studies the NPLIN effect in potassium chloride (KCl) solution on a liter scale. A batch cooling crystallizer coupled with an irradiation source in the form of the laser beam is investigated here as proof of the concept study. NPLIN experiments were conducted in batch crystallizer and were compared with the control experiments. Interestingly, the laser source reduced the induction time of nucleation compared to control experiments. This phenomenon showed that nucleation kinetics can be controlled using laser properties. Furthermore, it was observed experimentally that the nuclei generated by laser in an undersaturated solution can be grown to a detectable size provided the supersaturation is increased. It was also observed that the crystal number density was more with the multiple pulses as compared to a single pulse owing to the large exposed volume by irradiation of multiple pulses in agitated bulk solution. Finally, the offline particle size distribution (PSD) comparison was done. The dominant size of crystals was 100-200 microns for the control experiment whereas, it was 300-500 microns for the NPLIN experiment. It revealed a clear shift in the peak of the dominant size of crystals indicating a growth dominant event in NPLIN experiments. Appealingly, the nature of PSD generated by laser irradiation was found similar in all repetitions. It is hypothesized that the laser generates the seeds which grow in the metastable region.
This research study provides the basis for the NPLIN study in the system resembling industrial conditions. This, in turn, will aid in the understanding of the nucleation process and, ultimately, the optimization of industrial crystallization. The results obtained can also be used to develop mathematical models for particle size distribution.