Operation Strategy for Avoiding Oiling‐Out During the Anti‐Solvent Crystallization Based on Ternary Phase Diagram

Abstract

Oiling-out occurs during the crystallization process and frequently cause deterioration of the characteristics of crystalline particles. In this study, operation strategies to avoid the oiling-out in the anti-solvent crystallization are investigated based on the ternary phase diagram. It is found that oiling-out could be avoided by designing the trajectory of the operation point on the ternary phase diagram during the anti-solvent crystallization. Additionally, the characteristics of crystalline particles is improved by avoiding the oiling-out, which enables to obtain crystalline particles with high purity. The results show that the development of the operation method based on the ternary phase diagram is an effective strategy for avoiding the oiling-out and producing the crystalline particles with favorable characteristics.

Oiling‐Out in Industrial Crystallization of Organic Small Molecules: Mechanisms, Characterization, Regulation, and Applications

“…[58,59] Moreover, the solute has a structure with more hydroxyl groups, and the lower melting point is more likely to lead to oilingout. [60,61] Take reaction crystallization as an example. On the one hand, the relative molecular mass of the final product can be reduced by choosing a ligand with low molecular weight.…”

“…So, the greater the proportion of good solvent and the lower the initial concentration of solute will more likely avoids oilingout. [60] Al-Hanafi et al [54] showed that oiling-out can be avoided by controlling the initial concentration of indomethacin by analyzing the ternary phase diagram of indomethacin in a mixed solvent of DMSO and water. Lu et al [61] found that with idebenone at lower initial concentrations, oiling-out did not take place and the crystallization product had a higher purity.…”

“…[ 58,59 ] Moreover, the solute has a structure with more hydroxyl groups, and the lower melting point is more likely to lead to oiling‐out. [ 60,61 ]…”