The thesis focuses on integration of static and active mixing techniques in flow configurations to achieve an intensified crystallization process. An active mixing platform utilizing induced-charge electroosmosis (ICEO) is scaled-up and successfully utilized for reactive precipitation systems with low conductivity for the first time to better control the particle size distribution. The computational fluid dynamics simulations demonstrate that with ICEO uniform supersaturation can be achieved within a length that is about six times shorter compared to that without ICEO. Additionally, smaller silver chloride particles with a narrower size distribution and an improved yield for cocrystallization are obtained with application of ICEO compared to cases without ICEO. Next, the solution-mediat...[ Read more ]

The thesis focuses on integration of static and active mixing techniques in flow configurations to achieve an intensified crystallization process. An active mixing platform utilizing induced-charge electroosmosis (ICEO) is scaled-up and successfully utilized for reactive precipitation systems with low conductivity for the first time to better control the particle size distribution. The computational fluid dynamics simulations demonstrate that with ICEO uniform supersaturation can be achieved within a length that is about six times shorter compared to that without ICEO. Additionally, smaller silver chloride particles with a narrower size distribution and an improved yield for cocrystallization are obtained with application of ICEO compared to cases without ICEO. Next, the solution-mediated phase transformation (SMPT) of carbamazepine-dihydrate (CBZ-dh) crystals to pure carbamazepine-saccharin (CBZ-SAC) cocrystals is intensified through integration of a tubular flow crystallizer (TFC) with a stirred tank crystallizer (STC) during anti-solvent crystallization. Both CBZ-dh crystals and CBZ-SAC cocrystals nucleate earlier and the SMPT can be up to 75% faster when using a TFC compared to that in the standalone STC. The study suggests that differences in the process configuration influence crystallization kinetics. Next, a gapped Kenics static mixer crystallizer (gKTC) is integrated with a STC or a mixed suspension mixed product removal (MSMPR) crystallizer as a continuous, in-situ nuclei generating device to potentially address the challenges of traditional seeding methods. A higher total crystal count and yield are achieved in the STC when slurry is recirculated through the gKTC for longer durations. Moreover, lower induction times of crystals along with higher total crystal counts and higher throughputs are always achieved in an MSMPR crystallizer with either upstream or downstream integration of a gKTC compared to that in the standalone MSMPR crystallizer. Overall, the application of both ICEO or static mixers intensified the flow crystallization process through improved product quality attributes or increased process throughputs.