Impurity-induced acceleration of polymorphic conversion via crystalline solid solutions and the T–X phase diagrams of salicylic acid and 3-hydroxybenzoic acid†

Two T–X binary phase diagrams have been constructed between salicylic acid (SA) and two monotropic polymorphs of the isomer 3-hydroxybenzoic acid (3HBA). Crystalline solid solutions (CSS) were formed at all extremes of the phase diagrams. The solid-state miscibilities ranged from 0.5% up to 6% of the second component. The thermodynamically stable form I of 3HBA exhibited a higher solid state miscibility than form II of 3HBA across all investigated temperatures. The solubility changes induced by the different CSS were measured experimentally in 40 w% methanol in water at 25 °C and are presented in two ternary phase diagrams. The SA-rich CSS phase exhibited the highest solubility increase corresponding to 160% up to the solvus at 0.7% 3HBA in SA. The changes in solubility of the CSS phases belonging to the two 3HBA polymorphs were found to diverge with increasing incorporation of SA in the respective crystal lattices. This thermodynamic divergence in combination with the monotropic stability relationship caused the driving force for polymorphic conversion to increase with increasing SA content. This unusual scenario was demonstrated experimentally through the use of solution-mediated phase transformation (SMPT) experiments analyzed in situ by Raman. It was found that the incorporation of 0.5% SA in the crystal lattice of 3HBA form II caused the polymorphic conversion rate to form I to double, in comparison to when 3HBA is chemically pure. The current example thus demonstrates the thermodynamic context for how solid-state miscible impurities can expedite polymorphic conversions. This and other contributions showcase how the rates of crystallization can be enhanced or reduced solely based on formation of CSS with an impurity or additive, without accounting for any surface adsorption effects.