Polymorph control of sulfamerazine by ultrasonic irradiation

The effect of ultrasonic irradiation on the polymorph control of sulfamerazine (SMZ) in acetonitrile at 21 °C was studied. In the primary nucleation stage without ultrasonic irradiation, metastable form-I crystallized primarily from the supersaturated solution. Then, only form-I grew, although slowly, and the SMZ concentration reached the saturation point of form-I. SMZ showed a very low solvent-mediated polymorphic transformation rate owing to the small difference in solubility between its metastable form-I and stable form-II. The transformation from form-I to form-II hardly occurred, even when the suspension of form-I was maintained at 21 °C for a few days or weeks. Therefore, it was easier to obtain form-I than form-II by controlling only the degree of supersaturation. On the other hand, form-II could be obtained by supplying a certain amount of ultrasonic energy in the primary nucleation stage. In such cases, the nucleation rate and crystal growth rate were relatively high; the SMZ concentration reached the saturation point of form-II within one day. Furthermore, the solvent-mediated transformation was enhanced by ultrasonic irradiation. The SMZ concentration decreased when periodic ultrasonic irradiation was carried out a few hours after the SMZ concentration reached the saturation point of form-I. Finally, form-I transformed to form-II. Thus, for the production of either form, the polymorph of SMZ can be controlled with or without ultrasonic irradiation.