Influence of Agitation on Primary Nucleation in Stirred Tank Crystallizers

The influence of agitation on nucleation of butyl paraben and m-hydroxybenzoic acid polymorphs has been investigated through 330 cooling crystallization experiments. The induction time has been measured at different supersaturations and temperatures in three parallel jacketed vessels equipped with different overhead stirring agitators. In each case, the nucleating polymorph of m-hydroxybenzoic acid has been identified by infrared spectroscopy. The influences of agitation rate, impeller type, impeller diameter, impeller to bottom clearance, and the use of baffles have been investigated. A general trend in all of the experiments is that the induction time decreases with increasing agitation rate. Across all experiments with different fluid mechanics for the butyl paraben system, the induction time is correlated to the average energy dissipation rate raised to the power -0.3. It is shown that this dependence is consistent with a turbulent flow enhanced cluster coalescence mechanism. In experiments with m-hydroxybenzoic acid, the metastable form II was always obtained at higher nucleation driving force while both polymorphs were obtained at lower driving force. In the latter case, form I was obtained in the majority of experiments at low agitation rate (100 rpm) while form II was obtained in all experiments at higher agitation rate (≥300 rpm). (Graph Presented).