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Spherical Crystallization Based on Liquid-Liquid Phase Separation in a Reverse Antisolvent Crystallization Process
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DOI：10.1016/j.xphs.2024.01.016.png)
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Abstract
En 中文
Vanillin crystals undergo needle-like morphology that results in poor flowability, crystal breakage, and low packing density. The spherical crystallization technology can produce particles with improved flowability and stability. A reverse antisolvent crystallization based on liquid-liquid phase separation is proposed in this work to produce vanillin spherical agglomerates. Hansen Solubility Parameters are applied to explain the liquid-liquid phase separation (LLPS) phenomenon. The Pixact Crystallization Monitoring system is applied to in-situ monitor the whole process. A six-step spherical crystallization mechanism is revealed based on the recorded photos, including the generation of oil droplets, nucleation inside oil droplets, the coalescence and split of oil droplets, crystal growth and agglomeration, breakage of oil droplets, and attrition of agglomerates. Different working conditions are tested to explore the best operation parameters and a frequency-conversion stirring strategy is proposed to improve the production of spherical crystals. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
Keywords:
Liquid -liquid phase separation
Spherical crystallization
Hansen solubility parameters
Improved morphology
Vanillin
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