Nucleation kinetics of lovastatin in different solvents from metastable zone widths

Cooling crystallization of lovastatin in methanol, ethanol and acetone was carried out and the metastable zone widths in those solutions were determined experimentally by the polythermal method using a Turbidity Monitoring Technique. Two theoretical approaches, the self-consistent approach and classical 3D nucleation theory approach, were then employed to estimate the nucleation kinetics from the measured metastable zone width. The results suggested that nucleation in ethanol and acetone is instantaneous and follows polynuclear (PN) mechanism, while in methanol the nucleation is progressive with a high nucleation order. Because of the high solubility of lovastatin in these solvents, strong solute-solvent interactions exist, which make the activation energy for crystal formation different from that for self-diffusion.