Effect of Oscillatory Flow on Nucleation Kinetics of Butyl Paraben

Abstract

More than 165 induction times of butyl paraben-ethanol solution in batch moving fluid oscillation baffled crystallizer with various amplitudes (1-9 mm) and frequencies (1.0-9.0 Hz) have been determined to study the effect of COBR operating conditions on nucleation. The induction time decreases with increasing amplitude and frequency at power density below about 500 W/m 3 , however, a further increase of the frequency and amplitude leads to an increase of the induction time. The interfacial energies and pre-exponential factors in both homogeneous and heterogeneous nucleation are determined by Classical Nucleation Theory at oscillatory frequency 2.0 Hz and amplitudes of 3 mm or 5 mm both with and without net flow. To capture the shear rate conditions in oscillatory flow crystallisers, a Large Eddy Simulation approach in Computational Fluid Dynamics framework is applied. Under ideal conditions the shear rate distribution shows spatial and temporal periodicity and radially symmetry. The spatial distributions of the shear rate indicate an increase of average and maximum values of the shear rate with increasing amplitude and frequency. In

Continuous protein crystallisation platform and process: Case of lysozyme

“…The difference of the nucleation time was not obvious at very low shear rate range 0.05 -0.15 Hz in Figure 6. This non uniform mixing could lead to a lower homogeneous nucleation rate or secondary nucleation rate, which is in consistence with the literatures (Ploß and Mersmann, 1989;Yang et al, 2016). To achieve a shorter equilibrium time, a higher yield (lower final concentration of the crystallisation solution), and a better suspension of the crystals in the crystallisation solution, higher shear rate (i.e.…”

“…The change of the direction was dependent on the frequency, the direction changed 6 times (3 cycles) and 4 times (2 cycles) for 0.15 Hz and 0.1 Hz, respectively. It is noted that the velocity of the solution generated by syringe pump is different with that generated by piston pumps, which continuously changes all the time based on a sine function equation (Yang et al, 2016). Lysozyme solutions with 14 different concentrations were measured by UV absorbance at 280 nm, and the absorbance and lysozyme concentrations (C) were correlated by a linear equation.…”

“…In industrial downstream manufacturing, batch crystallisation is commonly used. However, continuous manufacturing including continuous crystallisation (Chew et al, 2004;Ni et al, 2004) draw more and more attentions from both industrials and academics (Briggs et al, 2015;Brown and Ni, 2011;Chew et al, 2004;Yang et al, 2016). Based on the principle of batch crystallizer, the mixed suspension mixed product removal crystallizer (MSMPR) is designed by connecting parallel batch crystalliser (Katoh and Katoh, 2000;Kwon et al, 2014).…”

“…Many research on continuous crystallizers have been investigated in mixed-suspension, mixed-product removal (MSMPR) crystallizer (Su et al, 2015;Yang et al, 2017), i.e. continuous stirred tank reactors (CSTRs) (Lai et al, 2015), plug flow reactor (PFR) (Neugebauer and Khinast, 2015), continuous (baffled) oscillatory flow reactor/crystalliser (OBR)/(COFC) (Chew et al, 2004;Jian and Ni, 2005;Yang et al, 2016).…”

“…Much efforts in continuous crystallisation have focused on small organic pharmaceuticals (Baxendale et al, 2015;McGlone et al, 2015). However, knowledge of oscillatory flow crystallisation, like mixing condition (Chew et al, 2004;Yang et al, 2016), nucleation (Yang et al, 2016), growth (Brown and Ni, 2011), process control (Briggs et al, 2015) on small organic pharmaceutical molecules can also help to develop and design protein continuous crystallisation process. However, the differences between crystallisation of proteins with small organic molecules are obvious.…”