Abstract The influence of ultrasound on liquid–liquid phase separation (LLPS) and polymorphism of vanillin in aqueous solution has been investigated for the first time by varying the ultrasonic parameters such as power, pulse rate and insonation time at ambient condition. Results reveal that the application of ultrasound controls the impact of LLPS and accelerates the nucleation of vanillin within a short period at lower levels of ultrasonic process parameters, and also enhances the quality of the nucleated crystals. Moreover, the application of ultrasound induces the nucleation of rare and metastable polymorph of vanillin Form II in aqueous solution. But, at higher levels of power, pulse rate and insonation time, the rate of LLPS is found increased and the quality of the crystals becomes deteriorated. Morphology of the nucleated polymorphs were identified through optical microscopy and confirmed by optical goniometry. The internal structure and thermal stability of the grown stable Form I and metastable Form II of vanillin were confirmed through powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses. Further, results suggest that the ultrasound has profound effect in controlling the LLPS and nucleation of vanillin polymorphs in aqueous solution.

中文翻译：

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超声波在控制香兰素多晶型物 I 和 II 的液-液相分离和成核中的作用

摘要 通过改变环境条件下的功率、脉冲频率和声波时间等超声参数，首次研究了超声对水溶液中液-液相分离（LLPS）和香兰素多晶型的影响。结果表明，超声的应用控制了 LLPS 的影响，并在较低的超声工艺参数水平下在短时间内加速了香兰素的成核，并提高了成核晶体的质量。此外，超声波的应用诱导稀有且亚稳的香草醛II型多晶型物在水溶液中成核。但是，在更高水平的功率、脉冲速率和声波时间下，发现 LLPS 的速率增加并且晶体的质量变差。成核多晶型物的形态通过光学显微镜鉴定并通过光学测角法确认。通过粉末 X 射线衍射 (PXRD) 和差示扫描量热法 (DSC) 分析证实了香兰素生长的稳定 I 型和亚稳 II 型的内部结构和热稳定性。此外，结果表明超声波在控制水溶液中香兰素多晶型物的 LLPS 和成核方面具有深远的影响。