Growth and Solvent-Mediated Phase Transition of Cimetidine Polymorphic Forms A and B

Abstract

For the organic compound cimetidine, which has seven polymorphic forms, the growth rates of form A (metastable) and B (stable) and the solvent-mediated phase transition rates from A to B were measured in 2-propanol solvent. At high supersaturation ratio (S_C,A = 3.6), with form-A seed, agglomerated crystals of form A were obtained without an induction period. With form-B seed, by contrast, form A nucleated heterogeneously on B seed’s surface and then grew to single-like crystals after the induction period. At low supersaturation ratio (S_A ≤ 1.3, S_B ≤ 1.7), the growth rate of form A was higher than that of form B at the same supersaturation ratio, S_i, based on their respective solubilities, but at the same solute concentration this tendency was reversed. At S_A = 1.0, a solvent-mediated phase transition took place, being controlled by the growth rate of form B. The growth rates of both forms at low supersaturation were proportional to the surface area of crystal and (S_i – 1)².