Precipitation of tretinoin and acetaminophen with solution enhanced dispersion by supercritical fluids (SEDS). Role of phase equilibria to optimize particle diameter

Precipitation of acetaminophen and tretinoin is performed using supercritical enhanced dispersion by supercritical fluids (SEDS), using carbon dioxide and ethanol as antisolvent and solvent respectively. In order to assure the no existence of immiscibilities and to determine the conditions at which the maximum attainable supersaturation is produced, it is performed a phase equilibria study of the ternary and binary systems with Peng–Robinson equation of state. The ternary equilibrium diagrams show that the maximum supersaturation matches with the mixture critical point given by the vapor–liquid diagram and also show information about the cosolvent effect of both antisolvent and solvent, proving in addition the no existence of immiscibilities at all the investigated conditions. These results are confirmed using a windowed cell. The effect of pressure, temperature and solution concentration in the precipitation process is discussed. The different particle diameters of the precipitated particles are explained with the aid of the phase equilibria diagrams, taking into account the position of experimental conditions with respect to the mixture critical point. The best results for both solids, spherical microparticles without aggregates and with a size around 0.5–0.75μm, are obtained just above the mixture critical point of the mixture antisolvent–solvent. [Display omitted] ► Two drugs have been precipitated with SEDS. ► The conditions were defined by modeling the ternary equilibria with PR-EOS. ► The results of the modelling were confirmed with a windowed cell. ► The role of phase equilibria in the particle size and morphology was discussed. ► The best PSD without aggregates were obtained just above the MCP.