Influence of Ultrasonic Irradiation on Crystal Nucleation, Morphology and Structural Properties of Maltol Polymorphs I and II From Aqueous Solution

The impact of ultrasound on the nucleation control and separation of maltol polymorphs in aqueous solution has been studied for the first time. The study involved varying ultrasound parameters such as power (ranging from 75 to 225 W), pulse rate (from 10% to 50%), and insonation time (2, 4, and 6 min) at room temperature and at different supersaturation levels. In addition to the expected effects of supersaturation on induction time, nucleation, and morphology of the maltol polymorphs, ultrasound is found to have a significant influence on nucleation control and separation of the polymorphs. The results reveal that ultrasound promotes the nucleation of maltol polymorphs with shorter induction times by creating nucleation hot spots through cavitation effect, and improves the quality of the crystals. Notably, under specific conditions, ultrasound induces the nucleation of a rare metastable Form-II polymorph of maltol in aqueous solution, while without ultrasound, only the stable Form-I polymorph is obtained. Morphology of the nucleated polymorphs is observed using in situ optical microscopy, and their structure is confirmed through powder X-ray diffraction (PXRD) and single crystal X-ray diffraction (SCXRD) analyses. Furthermore, thermal stability of the grown stable Form-I and metastable Form-II polymorphs of maltol is verified using differential scanning calorimetry (DSC).