Oiling-Out: Insights from Gibbsian Surface Thermodynamics by Stability Analysis

Area of Science:

• Chemical Engineering
• Physical Chemistry
• Crystallization Science

Background:

• Crystallization is crucial in pharmaceuticals.
• Cooling crystallization can lead to secondary liquid phase separation, known as "oiling out" or liquid-liquid phase separation (LLPS).

Purpose of the Study:

• Investigate the oiling-out phenomenon in a binary water-vanillin system.
• Analyze LLPS using Gibbsian surface thermodynamics and stability analysis.
• Determine conditions favoring droplet versus crystal formation.

Main Methods:

• Employed Gibbsian surface thermodynamics for stability analysis.
• Investigated three equilibrium cases: DLE, CL'E, and CLE.
• Utilized the NRTL model for activity coefficients to plot the phase diagram.
• Considered interfacial curvature effects on the phase diagram.

Main Results:

• Oiling out is justified by a lower energy barrier for droplet formation compared to crystal formation.
• Stable crystals possess significantly lower energy than stable droplets.
• Defined distinct regions for droplet and crystal formation on the metastable phase diagram based on supersaturation.

Conclusions:

• The study provides a thermodynamic basis for understanding oiling out in pharmaceutical crystallization.
• Identified critical factors influencing the competition between liquid-liquid phase separation and crystallization.
• Offers insights for controlling crystallization processes to prevent or promote oiling out.