Experimental verification for intensification mechanism and template role of nanobubbles as nucleation sites in reaction crystallization of diclofenac

Nanobubble has attracted extensive research attention due to their anomalous thermodynamic behavior while fundamental mechanisms remain elusive. This study aims to investigate the nucleation-crystallization of diclofenac in acidic environments as model reaction, employing in-situ methodologies to systematically analyze nanobubble synergy during nucleation-growth. Experimental verification of templating role and mechanism of nanobubbles as nucleation sites in reaction crystallization of diclofenac is performed. Kinetic studies reveal that nanobubbles can reduce the system's free energy barrier by 70.948 kJ/mol and decrease the preexponential factor to 2.2×10⁻⁶. Additionally, it is observed that highly dense nanobubble clusters can function as templates for synthesizing hollow particles, while increased intensity of reaction system leads to corresponding increasing in shell thickness.