Ultrasound-assisted separation and crystallization of metacetamol polymorphs

Abstract

The paper discusses the use of ultrasound in separating different polymorphic forms of metacetamol. The study examines the influence of various sonication parameters on the separation process, including nucleation time, morphology, and number of nucleation. The results indicate that lower sonication parameters lead to the nucleation of stable form I, while higher insonation time induces the nucleation of metacetamol hemihydrate. This helps to control the nucleation of stable form I and separate the hemihydrate from pure aqueous solution with reduced nucleation time. In situ optical microscopy was used to confirm the morphology of nucleated polymorphs. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were used to confirm the internal structure and thermal stability of the grown stable form I and hemihydrate crystals, respectively. The study concludes that ultrasonication is a reliable, robust and optimal method that significantly impacts the crystallization and separation of metacetamol polymorphs.