Nucleation kinetics of paracetamol-ethanol solutions from metastable zone widths

A study of the nucleation kinetics for a cooling crystallisation of paracetamol-ethanol solutions in a batch reactor is described in this paper. Metastable zone width (MSZW) experiments were conducted in order to estimate the nucleation kinetics of the system. Measured MSZWs can be affected by numerous process parameters, such as cooling rate, concentration, agitation rate, and working volume. Two theoretical approaches were employed to estimate the nucleation kinetics, the classical mass based approach of Nyvlt, and a more recent approach by Kubota, which also considers number density. Both approaches were found to produce similar estimates for the nucleation rates of the paracetamol-ethanol solutions as a function of supersaturation for an assumed nucleus size of 10 mu m. The theory of Kubota was found to predict satisfactory estimates for the induction time of the nucleation process from MSZW data. The induction time was observed to be independent of the solution temperature as suggested by Kubota's theory. This is a novel finding and serves to validate the induction time theory of Kubota. In this investigation, MSZWs were observed to decrease with increased levels of agitation and found to be independent of working volume. (C) 2010 Elsevier B.V. All rights reserved.