Primary nucleation of salicylamide: the influence of process conditions and solvent on the metastable zone width

Abstract

The onset of nucleation of salicylamide in organic solvents has been measured for a total of 2911 nucleation experiments at a constant cooling rate. The experiments are divided into series of different experimental conditions and for each series, the mean values and distributions of the nucleation events have been recorded. Generally, a significant spread in the onset of nucleation among identical repeated experiments was observed. The solvent and the cooling rate were found to be the factors exerting the greatest influence on the onset of nucleation, whereas the expected effects of the solution volume and the saturation temperature were largely absent. A correlation is observed between the supersaturation ratio at the average onset of nucleation and a group of parameters extracted from the pre-exponential factor in the classical nucleation rate equation, which is in agreement with the concept that a higher attachment frequency facilitates nucleation. It is also found that there can be a profound difference in the metastable zone width between experiments in open and closed crystallizers.