Thermodynamic analysis of micronization processes from gas-saturated solution

A thermodynamic analysis is developed to interpret the influence of temperature and pressure in the production of solid lipid nano- and microparticles by a high-pressure technique named particle from gas-saturated solution (PGSS). The pressure−temperature charts show three regions above the P−T solid−liquid−fluid coexistence curve, from which sub-cooled solid, solid−liquid, or liquid products can be obtained. The relation between the initial and final thermodynamic properties of the PGSS process were calculated by solving simultaneously the energy balance and a proper equation of state. The expansion of high-pressure CO2−lipid saturated solution through the micrometric nozzle was represented by a transformation at constant total enthalpy. To represent the equilibrium and thermodynamic behavior of CO2−lipid systems the perturbed-hard-sphere-chain theory (PHSCT) was used. As examples, CO2 absorption isotherms in lipids and residual properties of high-pressure tristearin−CO2 and tristearin−phosphatidylcoline−CO2 systems were calculated. Enthalpy of fusion of pure substances and formation enthalpy of microparticulate PGSS products were measured by differential scanning calorimetry (DSC). Pure lipid EOS parameters were estimated by a group contribution method, whereas the equation of state (EOS) interaction parameters were adjusted on the experimental melting point data under CO2 pressure, measured in a high-pressure windowed cell. Application of operative charts provides useful information in understanding the influence of temperature and pressure on the final properties of lipid particles produced by PGSS.