A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

Abstract

The metastable zone between the solubility curve and the crystallisation curve can be divided into two regions, separated by the secondary nucleation threshold. At a supersaturation less than that of the secondary nucleation threshold seeds will grow but not proliferate. At greater supersaturations, they will proliferate. Although this concept has been known in connection with the commercial crystallisation of sucrose and of lactose for almost a century it is virtually unrecognised beyond the sugar and dairy 10 industries. The consequences are explored of the existence of such a boundary on the crystallisation process and the influence on crystal size distribution. It is recognised that the secondary nucleation threshold is the 'seeded metastable limit', but there are important consequences of avoiding the latter term. Mullin's 'Latent Period' is shown to be closely related to the 'growth only' zone within the metastable zone.15

Secondary Nucleation from Nuclei Breeding and Its Quantitative Link with Fluid Shear Stress in Mixing: A Potential Approach for Precise Scale-up in Industrial Crystallization

“…A cooling crystallization technique is commonly employed in the chemical processes, and in order to understand its mechanism, the solubility, and the metastable zone width (MSZW) of a given system must be known. , The MSZW of a system can be divided into the growth-only zone and the crystal proliferation zone, where the boundary separating the two regions is termed as the secondary nucleation threshold . The nucleation kinetics, and hence the MSZW, are sensitive to process parameters such as mixing. , However, interpreting the MSZW under different mixing conditions at the laboratory scale can be helpful in understanding the process operating window which provides considerable information for the performance of the crystallization process.…”

Quantitative Link between Secondary Nucleation and Mixing Hydrodynamics in Batch Cooling Crystallization: A New Approach in Process Development

“…Moreover, within the MSZ of a crystallization system, SN has a smaller MSZ limit compared to PN. This is a well understood concept which has been reported frequently in the literature. ,,− …”

On the Effect of Secondary Nucleation on Deracemization through Temperature Cycles

“…Indeed, the secondary nucleation threshold, that is, the threshold supersaturation below which secondary nucleation is negligible, can for certain systems/operating conditions be extremely low, whereas contact secondary nucleation often requires a surprisingly small impact energy to be effective . Coupled with the fact that most temperature‐cycling deracemization experiments were performed in small scale equipment with magnetic stirring bars, the probability of secondary nucleation may be considered high even under seemingly mild conditions (small amplitude of temperature cycles and/or cooling rates).…”