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The growth rate of the stable polymorph A and the dissolution rate of the unstable polymorph B of L-histidine (L-his) in aqueous solution were experimentally determined at varying temperatures. The growth and dissolution kinetics were measured by means of desupersaturation and deundersaturation techniques, respectively. Both the growth and dissolution rates increase with higher temperature. At all temperatures studied, the dissolution rate of form B is faster than the growth rate of form A, indicating that the solution-mediated transformation of the polymorphs of L-his is likely to be controlled by the growth rate of form A. Both kinetics of the polymorphs of L-his will be used to characterize the polymorphic transformations and the overall crystallization rate of L-his.

Experimental measurements of the solution‐mediated transformation (SMT) of the metastable polymorph of DL‐methionine (α‐DL‐met) into the stable polymorph (γ‐DL‐met) in water were performed at 25 °C. These results were compared to models of the crystallization and the SMT of α‐DL‐met into γ‐DL‐met that were developed using the concept of the population balance equation (PBE) applied to both of the polymorphs. The growth, dissolution, and nucleation kinetic expressions obtained in a previous work were used in the models. It was found that the PBE models did not satisfactorily describe the SMT process of DL‐met when the measured crystallization and dissolution kinetics were used. There were large mismatches between the simulation and the experimental results. Modifying the model of the dissolution kinetics of α‐DL‐met enabled these mismatches to be lowered. The results showed that the SMT of DL‐met is controlled by the rate of dissolution of α‐DL‐met.

Antisolvent crystallization is the most common method to study solvent effects on polymorphic crystallization. L‐Histidine (L‐his) served as a model substance. Acetonitrile, acetone, and methanol were selected as antisolvents, with water as solvent. The formation of L‐his polymorphs in antisolvent crystallization as a function of supersaturation, antisolvent volume fraction, and temperature was studied. The solubility of polymorph A of L‐his decreased with increasing volume fraction of antisolvent and increased with higher temperature. The metastable polymorph B of L‐his was obtained at higher antisolvent volume fraction and supersaturation. At lower antisolvent volume fraction and supersaturation, a mixture of polymorphs A and B was detected.