Nucleation kinetics for primary, secondary and ultrasound-induced paracetamol crystallization

Abstract

Nucleation kinetics play a fundamental role in the design and control of crystallization processes. Understanding how crystallization conditions impact different nucleation mechanisms and the overall nucleation kinetics will lead to improved control over the nucleation process. Herein, a comparative study of the nucleation kinetics for primary, secondary and ultrasound-induced paracetamol crystallization in stirred microvials is presented. The results are evaluated using the classical nucleation theory by assessing the influence of the nucleation mechanism on the kinetic and thermodynamic nucleation parameter. Primary nucleation is promoted by the presence of impurities and exogeneous surfaces. It is also shown that seeding a single crystal into the solution lowers the thermodynamic threshold for nucleation, even without fragmentation of the parental crystal. The addition of ultrasound to the crystallization process on the other hand affects the kinetic part of the nucleation process.