TY - JOUR
T1 - Experimental Evaluation of Fluid Shear Stress Impact on Secondary Nucleation in a Solution Crystallization of Paracetamol
AU - Yousuf, Mustafa
AU - Frawley, Patrick J.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/11/7
Y1 - 2018/11/7
N2 - Cooling crystallization experiments were performed at 300 and 370 rpm over a range of saturation temperatures for the measurements of the metastable zone width (MSZW) using a large seed of paracetamol crystal in propan-2-ol solution. Particle imaging velocimetry (PIV) was used to quantify the fluid shear stress at each agitation rate employed, which was found to be 0.07 and 0.11 N/m2 respectively. A decrease in MSZW and growth only zone (GNZ) was observed with increasing shear stress, and the secondary nucleation threshold (SNT) was determined with a relative supersaturation ratio (Sr) of 1.17 at 0.07 N/m2 and 1.08 at 0.11 N/m2. Focused beam reflectance measurement (FBRM) displayed an increase in particle counts as nucleation progressed, with total counts increased by 25% at a higher fluid shear as more nuclei were being sheared off from the seed surface. Crystal nuclei breeding is proposed as a mechanism of secondary nucleation, where the surface of a seed crystal served as a nucleation site for the pre-existing clusters in the solution as was evident under scanning electron microscopy (SEM). Secondary nucleation and its link with fluid shear stress, a novel approach established in the present work, will offer a more precise model in process development and scale-up.
AB - Cooling crystallization experiments were performed at 300 and 370 rpm over a range of saturation temperatures for the measurements of the metastable zone width (MSZW) using a large seed of paracetamol crystal in propan-2-ol solution. Particle imaging velocimetry (PIV) was used to quantify the fluid shear stress at each agitation rate employed, which was found to be 0.07 and 0.11 N/m2 respectively. A decrease in MSZW and growth only zone (GNZ) was observed with increasing shear stress, and the secondary nucleation threshold (SNT) was determined with a relative supersaturation ratio (Sr) of 1.17 at 0.07 N/m2 and 1.08 at 0.11 N/m2. Focused beam reflectance measurement (FBRM) displayed an increase in particle counts as nucleation progressed, with total counts increased by 25% at a higher fluid shear as more nuclei were being sheared off from the seed surface. Crystal nuclei breeding is proposed as a mechanism of secondary nucleation, where the surface of a seed crystal served as a nucleation site for the pre-existing clusters in the solution as was evident under scanning electron microscopy (SEM). Secondary nucleation and its link with fluid shear stress, a novel approach established in the present work, will offer a more precise model in process development and scale-up.
UR - http://www.scopus.com/inward/record.url?scp=85054658800&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.8b01074
DO - 10.1021/acs.cgd.8b01074
M3 - Article
AN - SCOPUS:85054658800
SN - 1528-7483
VL - 18
SP - 6843
EP - 6852
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 11
ER -