The liquid volume expansion effect as a simple thermodynamic criterion in cholesterol micronization by supercritical assisted atomization

Abstract

The data of the liquid volume expansion could normally be used as one of the thermodynamic criteria to decide an appropriate process of supercritical fluid based micronization techniques. The liquid volume expansion data were predicted by the vapor–liquid phase equilibrium calculation of two binary systems (CO2/acetone and CO2/ethanol) using Peng–Robinson equation of state. The results indicated that the liquid volume expansion of CO2/acetone mixtures was much larger than that of CO2/ethanol mixtures at the specified temperature and pressure. According to the thermodynamic criterion, acetone was affirmed to be a good solvent for supercritical antisolvent process (SAS) due to the higher liquid volume expansion, while ethanol was suitable for supercritical assisted atomization (SAA). This thermodynamic criterion was applied to the micronization of cholesterol and spherical particles were prepared in various organic solvents by SAA with an enhanced mixer. When the liquid volume expansion was lower than 80%, SAA could be successfully conducted and the good morphology and size distribution of the cholesterol particles were obtained. If the liquid volume expansion was higher than 140%, the solute would precipitate in the mixer before the atomization leading to the blockage of nozzle due to the antisolvent effect. In that case, the cholesterol particles in the mixer maintained the same morphology and crystalline structure as the SAS processed. This criterion is a practical and accessible tool to successfully implement the SAA process avoiding undesirable precipitation in the mixer.