Particle Breakage: Limiting Conditions for Crystal–Crystallizer Collisions

Abstract

Two prominent theories surround the origin of secondary nuclei in batch crystallization experiments. Traditionally, the generation of secondary nuclei has been attributed to attrition breeding, resulting from collisions between crystals, impeller, and vessel geometry. Mechanistically, it is assumed that the collision of crystals leads to the generation of fine particles and nucleation sites. More recently, an alternative mechanism has received considerable attention, namely, cluster breeding secondary nucleation whereby the source of fine particles is attributed to clusters in solution. In the present work, a detailed experimental investigation of particle wall collisions of active pharmaceutical ingredient crystals is conducted. A pressurized test rig was developed whereby crystals in suspension were fired through a nozzle perpendicular to a stainless steel target. Using shadowgraphy, direct imaging particle-plane collisions are captured for crystals between 100−400 μm as they approach a target surface with initial velocities of up to 10 m/s. Crystals approaching a target surface are seen to be cushioned by a squeeze film boundary layer, greatly reducing their impact velocities. Furthermore, below a critical freestream particle Reynolds number, complete particle arrest was observed, preventing contact with the target surface entirely. This work provides further evidence to suggest that indeed secondary nucleation cannot be accounted for through particle−impeller breakage events. The alternative crystal breeding ideology is therefore further supported.

A Review of Experimental Methods for Nucleation Rate Determination in Large-Volume Batch and Microfluidic Crystallization

“…In large volume stirred batch crystallizers it is even more difficult to quantify the effect of secondary nucleation. Tyrrell et al have shown that the fluid dynamics of a moving impeller might protect crystals from attrition in a large volume crystallizer 164 . Protection from the impeller alone is, however, not enough to prevent secondary nuclei: experiments have shown that fluid flow (shear) is sufficient to generate secondary nuclei 165 , although it has also been reported that this shear nucleation might be less effective 166 .…”

Secondary Nucleation by Interparticle Energies. II. Kinetics

“…Traditionally, secondary nucleation has been largely attributed to microbreakages of seed crystals caused by crystal-impeller collisions, 3 that is, attrition. 1 , 4 , 5 However, recent research has noted that this mechanism cannot describe secondary nucleation completely, 3 , 6 − 13 based on two main reasons. First, secondary nucleation can occur even when the crystal microbreakages are prevented by precluding any crystal-impeller collision.…”

Revealing cracking and breakage behaviours of gibbsite particles

“…Based on the above mentioned results, a mechanism of calcined gibbsite breakage is proposed and given in Figure 4c and d. The gibbsite particle breakage on the crystallite is initiated by the cracks on the surface, since the cracks are reported to be fragile parts where the stress caused by external force is likely to accumulate 18,19 . The breakage then extends into the crystallite and causes the cleavage of crystallites.…”

“…The calcination ramping rate and the size of crystallites consisting of gibbsite particles can influence the calcined gibbsite particle strength by influencing the total crack volume and crack width distribution on the calcined particles since cracks can be the defect point where breakage is likely to be initiated 18,19 . The particle embrittlement caused by cracks is more significant in gibbsite particles consisting of larger crystallites and calcined with lower ramping rates since these samples tend to generate cracks with increased total volume and crack width distribution.…”

“…On the other hand, the cracks on gibbsite grain boundary are initiated on the particle surface and then grow into the particle bulk with further calcination 17 . The cracks generated during calcination are considered to cause particle embrittlement, and it is the external force applied to the particles that directly initiate particle breakage 13,[18][19][20] . In this work, we first aimed to analyse the impact of the calcination method and particle morphology on gibbsite particles' cracking behaviour during static calcination.…”