A combinational supercritical CO2 system for nanoparticle preparation of indomethacin

An improved system using both supercritical antisolvent precipitation and rapid expansion from supercritical to aqueous solution (RESAS) was proposed to overcome the problem of low solubility of medicinal substances in scCO2. When the ethanol solution with IMC was sprayed into the vessel purged with scCO2, no precipitation of IMC was observed if the CO2 pressure was more than 15 MPa at 40 °C. This indicates that very small droplets of the ethanol solution with IMC could disperse in the high pressure CO2. After expansion into distilled water using an RESAS device, this same solution, in CO2 at high pressure, produced submicron particles of IMC. For the pharmaceutical application, the IMC suspension was freeze-dried and re-dispersed to the aqueous media. SEM images of freeze-dried sample showed that the suspension was composed of submicron particles with 300–500 nm. Although the average particle size of re-dispersed IMC related significantly to the pressure and temperature in the vessel on scCO2 processing, the freeze-dried sample of the IMC suspension after the treatment shows good redispersibility as a nanosuspension. This apparatus is found to be a promising way to produce fine crystals of IMC with a high yield.