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Process Intensification through Continuous Spherical Crystallization Using an Oscillatory Flow Baffled Crystallizer
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DOI：10.1021/acs.cgd.7b00731.png)
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Abstract
En 中文
Drug substance purification by crystallization is a key interface in going from drug substance synthesis to final formulation and can often be a bottleneck in process efficiency. There has been increased importance in the development of continuous crystallization systems of active pharmaceutical ingredients to produce crystals with targeted physical and biopharmaceutical properties. Continuous spherical crystallization (CSC) is a process intensification technique that can address many of the present flaws (e.g., size distribution, downstream processing efficiency) of traditional crystallization systems. In this study, a novel concept and method in the field of process intensification through continuous spherical crystallization is proposed. This study is based on performing crystallization/spherical agglomeration in an oscillatory flow baffled crystallizer (OFBC). OFBCs are comparable to plug flow crystallizers (PFCs) in that they are both tubular crystallizers; however, the OFBC has periodically spaced orifice baffles with oscillatory motion overlapped on the net flow. Independent crystallization mechanisms can theoretically be achieved through spatially distributed solution, solvent, antisolvent, and bridging liquid addition, offering more control of each mechanism. However, our studies showed that the OFBC allowed for spatially distributed addition of solvents but achieving control of each mechanism individually was not attainable due to the back mixing of the system.
Keywords:
PRODUCT-REMOVAL CRYSTALLIZATION
MIXED-SUSPENSION
BENZOIC-ACID
TECHNOLOGY
AGGLOMERATION
SYSTEM
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IF:
3.4
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1.6W
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3.5W
