Determination of metastable zone width and nucleation kinetics for combined cooling and antisolvent crystallization of L-asparagine monohydrate in water-isopropanol mixture

The metastable zone width (MSZW) was measured for combined cooling and antisolvent crystallization of L-asparagine monohydrate (LAM) in water-isopropanol solution by conventional polythermal method. The effects of cooling rate, antisolvent flow rate and saturation temperature on the MSZW were investigated and analysed using both statistical and theoretical models. The relationship of MSZW with these factors are more complex compared to cooling-only or antisolvent-only crystallization. For each of these three factors, a range of values were determined where the MSZW behaves in a more predictable manner and follows the behaviour of cooling-only crystallization. The effect of antisolvent flow rate was more pronounced compared to cooling rate in case of combined cooling and antisolvent crystallization of LAM. The obtained MSZW data were also used for the estimation of nucleation kinetics using the method proposed by Kubota.