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J Pharm Sci ; 113(6): 1616-1623, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38311170

RESUMO

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.


Assuntos
Benzaldeídos , Cristalização , Solubilidade , Solventes , Cristalização/métodos , Solventes/química , Benzaldeídos/química , Tamanho da Partícula , Transição de Fase , Separação de Fases
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