Dirty Nucleation\nof Salicylic Acid

Nucleation studies have been conducted on salicylic acid\nin the\npresence of solid-state miscible impurities. Crystallizations were\ncarried\nout at different seed loads and supersaturation ratios while monitoring\nthe solid and liquid phase compositions. The results show that crystallizations\ndominated by nucleation caused higher levels of impurity entrapment\nthan crystallizations dominated by crystal growth at the same supersaturation\nratio. The solid phase was the most enriched in impurities following\nnucleation and decreased linearly with the product yield until reaching\nthermodynamic equilibrium, as determined by the phase equilibria of\nthe respective solid solutions. It was also found that low-level impurities\nwere enriched to a higher degree in the early forming solid phase\nin crystallizations dominated by nucleation. Furthermore, metastable\nzone width (MZW) measurements of salicylic acid were carried out in\nthe presence and absence of impurities. While the addition of the\nknown solid-state miscible impurities did not exert a strong effect\non the MZW, the removal of already present low-level impurities by\nrepeated recrystallizations showed a marked increase in the apparent\nsupersaturation ratio needed to induce primary nucleation. The results\nsuggest that impurities accumulate in the solid phase at the onset\nof nucleation. The incorporation of impurities within the nuclei is\nexpected to take place to reduce the free energy barrier to nucleation\nby lowering the surface free energy. At the same time, the early forming\nsolid phase is comprised of metastable crystalline solid solution\nphases that are relatively disordered and exhibit higher solvent solubility\nthan macroscale equilibrium. Comparative analyses are made to the\nclassical and nonclassical nucleation theories conceptually, demonstrating\nhow the level of supersaturation and material purity may impact the\nstructural properties of the nuclei, which may lead to different nucleation\npathways. Furthermore, the treatment of solid solution formation at\nthe onset of nucleation is compared to several common empirical observations\nrelating to the ordering and stochasticity of crystal nucleation.\nAs an example, it is demonstrated how the creation of polymorphic\nmetastable solid solutions following nucleation provides a thermodynamic\nexplanation for Ostwald’s rule of stages and the appearance\nand disappearance of new polymorphs. Finally, the structural hysteresis\nobtained via the recrystallization or dissolution of crystalline solid\nsolutions is used to explain the so-called solution memory effect.