Drug Nano-Particles Formation by Supercritical Rapid Expansion Method; Operational Condition Effects Investigation

Abstract

<em>Dissolution pressure and nozzle temperature effects on particle size and distribution were investigated for RESS (Rapid Expansion of Supercritical Solution) process. Supercritical CO₂ was used as solvent and Ibuprofen was applied as the model component in all runs. The resulting Ibuprofen nano-particles (about 50 nm in optimized runs) were analyzed by SEM and laser diffraction particle size analyzer systems. Results show that in low supercritical pressure ranges, depending on the solvent and solid component properties (Lower than 105 bar for Ibuprofen-CO₂ system), nozzle temperature should be as low as possible (80-90˚C for Ibuprofen-CO₂ system). In the other hand in high supercritical pressure ranges (above 105 bar), high nozzle temperatures work better. The border line of these two areas depends on the solvent phase behavior. Rapid Expansion of Supercritical Solution into a liquid solvent (RESOLV) was also studied with and without the presence of surfactant and compared with RESS process by measuring of formed particles size, size distribution and dissolution rate. Results show that the RESS process generally creates better conditions for achieving fine and uniform organic powders (with mean particles size of 40-180 nm), in contrast to the RESOLV method (minimum particles size of 80-400 nm).</em>