Seed-Assisted Effects on Solution-Mediated Phase Transformation: A Case Study of l-Histidine in Antisolvent Crystallization

Abstract

In this study, the effects of crystal nucleation− growth on subsequent solvent-mediated phase transformation experiments of L-histidine (L-his) in antisolvent crystallization were performed at 298.15 K. The unexpected acceleration of the overall transformation rate in antisolvent crystallization with solution-mediated phase transformation was found for a methanol volume fraction of 0.35 < x 2 < 0.60. Interestingly, concomitant polymorphs were obtained for a methanol volume fraction of 0.30 ⩽ x 2 ⩽ 0.65 in antisolvent crystallization, whereas only form B was observed for other volume fractions of methanol, which indicated that the concomitant polymorphic phenomenon was the main reason for the accelerated transformation rate in antisolvent crystallization. Furthermore, seed-assisted experiments and suspended solution-mediated phase transformation experiments were designed to uncover the role of the nucleation of form A accompanying with form B in the subsequent transformation process.

Theoretical Model and Experimental Investigations on Solution-Mediated Polymorphic Transformation of Theophylline: From Polymorph I to Polymorph II

“…For instance, polymorphic transformation has a large effect on the shelf life of the drug [3]. Considering that solution-mediated phase transformation is commonly observed during pharmaceutical production [4], a good understanding of the thermodynamic and kinetic properties of the solution-mediated polymorphic transformation is essential for the determination of the most thermodynamically stable form at room temperature during drug development and production to ensure the quality of the drug [5].…”

Influence of Solvents on Solution‐Mediated Polymorphic Transformation of the Polymorphs of L‐Histidine

“…In literature, L ‐his is known to crystallize in a metastable polymorph B and a stable polymorph A , , . Kitamura et al , studied the formation and transformation of polymorphs of L ‐his by rapidly cooling aqueous and ethanol‐water solutions.…”

“…The rate of the generation of supersaturation is highly dependent on the addition rate of the antisolvent. Antisolvents also have an impact on the kinetics of crystallization , and polymorphic crystallization and SMPT , , .…”

“…Liu et al investigated the SMPT of the polymorph of L ‐his in methanol‐water solution by antisolvent crystallization. The concomitant polymorphs were obtained at a methanol volume fraction in the range of 0.3–0.65 and at 25 °C.…”

Interplay between Thermodynamics and Kinetics on Polymorphic Behavior of Vortioxetine Hydrobromide in Reactive Crystallization

“…Evidently, compared to the overall nucleation and growth rate of form B, the overall dissolution rate of form A is faster. Thus, the rate-controlling step at this stage is the stable form B’s nucleation and growth. − Afterward, when the metastable form A dissolved completely, the solution concentration consumed by nucleation and growth of form B could not be replenished. Hence, the solution concentration started to decrease again until the solubility of the stable form B was reached.…”