This work details the estimation of the secondary nucleation kinetics of paracetamol in ethanol
solutions for cooling crystallisation processes, by means of isothermal under-seeded batch
experiments. A numerical model, incorporating the population balance equation and the method of
moments, has been developed to describe the seeding process for a typical cooling crystallisation
process, accounting for the primary and secondary nucleation and subsequent crystal growth.
Primary nucleation and growth kinetics have been previously evaluated from induction time
experiments, and isothermal seeded batch experiments, respectively, allowing the secondary
nucleation rate to be evaluated for a wide range of experimental conditions. The experimental
technique involved the utilisation of two in-situ Process Analytical Techniques (PAT), with an
Focused Beam Reflectance Measurement (FBRM®) utilised to qualitatively indicate the occurrence
of secondary nucleation and an Attenuated Total Reflectance - Fourier Transform Infrared (ATRFTIR)
probe employed for the online monitoring of solute concentration. Initial Particle Size
Distributions (PSD) were used in conjunction with desupersaturation profiles to determine the
secondary nucleation rate as a function of supersaturation, temperature and crystal surface area.
Furthermore, the effects of agitation rate on the secondary nucleation rate were also investigated.
Experimental parameters were compared to the model simulation, with the accuracy of the
estimated secondary nucleation kinetics validated by means of the final product PSD and solute
concentration