(737c) A Novel Approach into Secondary Nucleation and Crystal Growth, Controlled Particle Size Distribution, Using a Large Single Seed Crystal in Solution Crystallization

Secondary nucleation by means of seed crystals is extensively employed in crystallization process and remained a noteworthy consideration of research in recent years, but its in-depth understanding particularly at molecular level remained elusive until recently, molecular dynamic simulations provided an insight to it, i.e. crystal nuclei breeding. However, seed crystals are typically dispersed in solution, it becomes difficult to decouple nuclei breeding from attrition-enhanced secondary nucleation. In this work, a novel approach was used to experimentally investigate the mechanism of crystal nuclei breeding as an origin of secondary nucleation and its link with fluid shear, using a large single crystal of paracetamol (size = 15mm x 12mm) in propan-2-ol. The crystal was held stationary in the stirring vessel using a specially design crystal holder, to eliminate the possibility of enhanced secondary nucleation due to crystal attrition or breakage during agitation. The experiments were done in a low supersaturation (S_o = 1.0) at stirring speed of 300 and 370 rpm. Particle imaging velocimetry (PIV) was used to quantify the fluid shear rate at each stirring speed using a high-speed camera and laser illuminated sheet. Laser diffraction was used to perceive the onset of secondary nucleation using a focused beam of red laser passing through the vessel which was calibrated to detect the particle size as small as 20 Æžm. Focused beam reflectance measurement (FBRM) was used for real time tracking of particles which displayed a significant increase in particle counts with an increase in shear rate at higher rpm. At a high fluid shear, the MSZW exhibited a decrease in secondary nucleation threshold with a relative supersaturation ratio of 1.17 at 300 rpm and 1.08 at 370 rpm. Below this threshold, a growth only zone was apparent which was validated using the scanning electron microscopy (SEM). PSD data was measured on a volume basis with increasing number of fines at a higher share rate as expected. Since, no crystal attrition and breakage were involved in the onset of secondary nucleation, these results provided experimental evidence that support the hypothesized nuclei breeding mechanism. Further evidence from the SEM images of the seed crystal, showed the formation of alternate layered pattern of the surface growth and the existence of very fine crystallite layers attached to it. It is proposed that the surface of seed crystal served as a catalyst for the pre-existing clusters in the solution to attach and nucleate to form crystallites, which then sheared off by the fluid flow. The experiments presented an excellent repeatability over MSZW and growth only zone at specific shear rate, particularly the revelation of controlled particle size distribution elucidates the significance of fluid shear on the secondary nucleation using a single seed crystal. Controlled particle size distribution is an imperative quality factor in crystallization and the quality of crystalline product. This approach can offer a more precise modelling in process scale-up and manufacturing in industry.