Control of Crystal Size during Oiling Out Crystallization of an API

Abstract

The oiling out crystallization of a pharmaceutical compound API-T dissolved in acetone/water was conducted using a 100 mL crystallizer, and the effect of oil droplets on the resulting crystal size was investigated. The size of oil droplets was controlled by varying agitation speed, and the resulting crystal size decreased with an increase in the size of oil droplets, namely, with a decrease in agitation speed. The observed phenomenon could be explained by the difference of nucleation rate in large and small droplets. The generation of small crystals was caused by the ease of primary and secondary nucleation in large droplets. A decrease in oil droplet size restrained the primary nucleation and also the secondary nucleation. In this case, the small amount of crystals that were released to the continuous phase grew by absorbing small droplets. On the other hand, in single-phase crystallization without liquid−liquid phase separation, the crystal size did not depend on agitation speed.

Diffusion controlling porphyrin assembled structures

“…But our understanding on why and how the solvents play their role in shaping these structures is limited. Some researcher ascribed solvents effect to the change of supersaturation because the supersaturation ratio influences the relative growth rate of different facets and therefore leads to the formation of diverse structures at various solvents [33,34]. Others believed that the solvent influence the structure development of materials by interacting with reactants [35,36].…”

Influence of Liquid‐Liquid Phase Separation on the Crystallization of L‐Menthol from Water

“…With respect to crystal properties, Veesler and co‐workers were able to perform an experiment using LLPS to obtain spherical agglomerates with favorable downstream properties, effectively combining crystallization and granulation , . Additionally, recent developments demonstrated that by controlling the droplet size, as a function of the impeller's stirring speed, the crystal size could be influenced . In another case, oiling‐out has been shown to be a feasible way to attain more compact and larger crystals , providing a competitive advantage with respect to the case where oiling‐out was absent.…”

Control over phase separation and nucleation using a optical-tweezing potential

“…The metastable critical point idea found some traction in the chemical engineering community where it was related to the phenomenon of "oiling out" without too much detailed theoretical analysis. 23,34,35 Could liquid-liquid phase separation, oiling out, pre-nucleation clusters, and laser-induced nucleation all be aspects of the same phenomenon? 26,36,37 On approaching a liquid-liquid demixing critical point, concentration fluctuations increase.…”