Influence of Fluid Shear on Primary  Nucleation of Organic Compounds in Solution  Jin Liu  Doctoral Thesis

Sammanfattning: In this work, three experimental systems have been used to study the influence of agitation/ fluid shear on primary nucleation. Three organic compounds have been used with different solvents, i.e. butyl paraben in ethanol solution, curcumin in ethanol solution and m-hydroxybenzoic acid in 1-propanol solution. Induction time and polymorphic outcome were investigated through around 3500 cooling crystallization experiments under different supersaturations and temperatures. It is clearly shown that induction time is influenced by agitation. In the first set of experiments, a large number of experiments have been done in capped vials stirred with magnetic stir bars. It was found that the induction time decreases with increasing agitation rate in the low agitation region. However, further increase in agitation leads to an increase again in the induction time, which is attributed to the irregular rotating behavior of the stir bar at higher rotation rate. In the second set of experiments, relatively uniform shear rate has been generated using a Taylor-Couette flow device. The induction time is found to be inversely related to the fluid shear rate. By fitting the parameters of the classical nucleation theory to experimental data, it is shown that the results can be explained as an influence on the pre-exponential factor while the critical free energy of nucleation is independent of the rotation rate as expected. In the third set of experiments, the influence of agitation conditions on nucleation have been investigated in three parallel jacketed, agitated crystallizers equipped with different types of overhead agitators. Several parameters, including agitation rate, impeller type and size, impeller to bottom clearance and the presence of baffles have been studied. Across all experiments with different fluid mechanics in Taylor-Couette flow device and jacketed crystallizer for the butyl paraben system the induction time is correlated to the energy dissipation rate raised to power 0.3. Through a comprehensive review of literature and analysis based on our experimental results, the shear enhanced pre-nucleation clusters coalescence is identified as the most plausible mechanism. The polymorphic outcome in nucleation experiments of m-hydroxybenzoic acid is also influenced by agitation, especially at low driving force of nucleation. In the vial experiments, the proportion of form I decreases at intermediate agitation rates (200 and 400 rpm), where the induction time of form II is more reduced compared to form I. In both Taylor-Couette and jacketed crystallizer experiments, form I is obtained in most experiments at low agitation rate (100 rpm) while form II is obtained in most experiments at higher agitation rates (≥300 rpm). The results are explained by comparing the molecular packing and hydrogen bonding in the structures of both polymorphs.