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 CO 2 −lipid saturated solution through the micrometric nozzle was represented by a transformation at constant total enthalpy. To represent the equilibrium and thermodynamic behavior of CO 2 −lipid systems the perturbed-hard-sphere-chain theory (PHSCT) was used. As examples, CO 2 absorption isotherms in lipids and residual properties of high-pressure tristearin−CO 2 and tristearin−phosphatidylcoline−CO 2 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 CO 2 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.