Fluidic devices for continuous crystallization: modelling and experimentation

Crystallization is a crucial separation process used in manufacturing a wide range of products. Traditionally, crystallization is practiced in mechanically agitated vessels operated in a batch or semi-batch mode, particularly in the pharmaceutical industry. In recent years, there is an increasing interest in using fluidic devices without any moving parts for crystallization. In this work, flow, mixing and potential application for anti-solvent crystallization of two such fluidic devices namely, fluidic oscillator (FO) and vortex-based cavitation device (VD) were investigated. Both devices do not contain any moving parts and offer an attractive way to realize the mixing and transport processes required for anti-solvent crystallization. Initially, these two devices were used to demonstrate their application to enhance mixing for anti-solvent crystallization by coupling them with a traditional agitated crystallizer operated in a batch mode. Antisolvent crystallization of paracetamol (PCM) using the PCM-methanol-water system was considered as a model crystallization process in this work. Experiments carried out with these two devices demonstrated that the considered fluidic devices offer better mixing characteristics and can effectively be used for crystallization and controlling crystal size distribution (CSD). Encouraged by these proof-of-concept results, systematic computational and experimental investigations of flow and mixing in these devices were undertaken, which formed the main body of this work. The flow in FO is characterized by inherently oscillating jets. Computational fluid dynamics (CFD) based models were developed to simulate inherently unsteady flow in FOs. After establishing grid independence, the influence of selection of the turbulence model on predicted jet oscillation frequency was investigated, and realizable 𝑘 − 𝜀 turbulence model with enhanced wall treatment was selected. Jet oscillation frequency was experimentally measured. It was observed that the inception of jet oscillations in FO occurs once the inlet Reynolds number is higher than a certain number (868-1736) – denoted by inception Reynolds number. The experimental data of pressure fluctuations acquired by pressure sensors and flow measurements using laser Doppler anemometer (LDA) were used for evaluating computational models. The computational model was validated by comparing simulated results with experimental data. The validated computational model was used to simulate unsteady flow patterns, jet oscillations, residence time distribution (RTD), and mixing. The model was used to investigate the influence of key design parameters of FO. Based on these experimental and computational studies, the width of the backflow limb was found to be the most important design parameter in terms of maximizing the jet oscillation frequency. The computational model was then extended to simulate solid-liquid flow in FO. The effect of solid loading (1 – 5 % solid loading) on the jet dynamics was investigated, to evaluate the suitability of FO for continuous crystallization. The model was also used to investigate the influence of particle size (75- 175 µm) and solids loading on flow and residence time distributions of solids in FO. The cavitating flow in VD, which may intensify mixing and particle breakage, was computationally and experimentally investigated to understand the influence of viscosity (1 – 208 cp) and device scale on cavitation inception and pressure drop. Correlations were developed to cover a wide range of operating parameters and device scales to estimate pressure drop and cavitation inception. The influence of the number of inlets on the cavitating performance of the VD was also investigated. These detailed results on flow characteristics of FO and VD provide a sound basis for harnessing these devices for continuous anti-solvent crystallization. Such an application is then demonstrated as the last part of this thesis, where continuous anti-solvent crystallization of PCM was carried out using FO. For augmenting the residence time, two FOs in series or one FO combined with a helical coil were used for crystallization experiments. The results of anti-solvent crystallization obtained with these fluidic devices were compared with the reference case of continuous stirred tank crystallizer. The CSD and overall yield obtained from these continuous anti-solvent crystallization experiments were described by population balance models (PBM) by using fitted kinetic parameters. The possibility of integrating developed CFD models with PBM for simulating CSD is demonstrated. The approach, models and experimental data presented in this work will be useful for developing and using intensified fluidic devices such as FO and VD for continuous anti-solvent crystallization.