Solid-liquid equilibria of multicomponent lipid mixtures under CO2 pressure: Measurement and thermodynamic modeling

A method for evaluating solid-liquid equilibria of mixtures of lipids and carbon dioxide (CO2) under pressure is developed and presented in this article. Experimental measurements by high-pressure differential scanning calorimetry (DSC) are performed to determine solid-liquid transition temperatures as a function of composition. These data are used to develop a simplified approach for thermodynamic modeling, i.e. correlation and prediction, of the solid-liquid equilibria. The model requires fewer pure component properties in comparison with cubic equations of state: the solid-state fugacity is determined with reference to the subcooled liquid state while regular solution theory is applied for the calculation of liquid-phase activity coefficients. Application of the model is demonstrated for mixtures of ceramide 3A and cholesterol in compressed CO2 in the range of pressure from 0.1 to 6.1 MPa. A satisfactory correlation of solid-liquid equilibria is obtained for binary systems consisting of either the lipid mixture or one lipid in compressed CO2. With the fitted binary interactions parameters, the eutectic temperature of the ternary mixture is predicted to within 1°C of the experimental value in the range of pressure considered. The proposed evaluation method looks sufficiently accurate for representing multiphase equilibria of lipid mixtures in compressed CO2 and has direct application to gas-assisted micronization processes such as PGSS (Particles from Gas-Saturated Solution).