Dirty Nucleation of Salicylic Acid

Abstract

Nucleation studies have been conducted on salicylic acid in the presence of solid-state miscible impurities. Crystallizations were carried out at different seed loads and supersaturation ratios while monitoring the solid and liquid phase compositions. The results show that crystallizations dominated by nucleation caused higher levels of impurity entrapment than crystallizations dominated by crystal growth at the same supersaturation ratio. The solid phase was the most enriched in impurities following nucleation and decreased linearly with the product yield until reaching thermodynamic equilibrium, as determined by the phase equilibria of the respective solid solutions. It was also found that low-level impurities were enriched to a higher degree in the early forming solid phase in crystallizations dominated by nucleation. Furthermore, metastable zone width (MZW) measurements of salicylic acid were carried out in the presence and absence of impurities. While the addition of the known solid-state miscible impurities did not exert a strong effect on the MZW, the removal of already present low-level impurities by repeated recrystallizations showed a marked increase in the apparent supersaturation ratio needed to induce primary nucleation. The results suggest that impurities accumulate in the solid phase at the onset of nucleation. The incorporation of impurities within the nuclei is expected to take place to reduce the free energy barrier to nucleation by lowering the surface free energy. At the same time, the early forming solid phase is comprised of metastable crystalline solid solution phases that are relatively disordered and exhibit higher solvent solubility than macroscale equilibrium. Comparative analyses are made to the classical and nonclassical nucleation theories conceptually, demonstrating how the level of supersaturation and material purity may impact the structural properties of the nuclei, which may lead to different nucleation pathways. Furthermore, the treatment of solid solution formation at the onset of nucleation is compared to several common empirical observations relating to the ordering and stochasticity of crystal nucleation. As an example, it is demonstrated how the creation of polymorphic metastable solid solutions following nucleation provides a thermodynamic explanation for Ostwald’s rule of stages and the appearance and disappearance of new polymorphs. Finally, the structural hysteresis obtained via the recrystallization or dissolution of crystalline solid solutions is used to explain the so-called solution memory effect.