Production of ultrafine drug particles through rapid expansion of supercritical solution; a statistical approach

Abstract

Performance of Rapid Expansion of Supercritical Solution (RESS) process, under different operation conditions, was conditions were evaluated through the analysis of the drug particle characteristics. The original particles of Lynestrenol with average size of 10μm as a drug material were dissolved in supercritical CO2 and then expanded rapidly through a nozzle with 0.6mm diameter. The effect of temperature, pressure and fraction of solid co-solvent (menthol) was investigated by a two-level factorial experimental design. Our results showed that the pre-expansion pressure, temperature and solid co-solvent can significantly affect the morphology and size of the precipitated particles. In addition, the binary interaction effects of temperature–pressure and pressure–cosolvent were observed to apparently influence the size of outlet particles. In the temperature range from 45 to 60°C, pressures from 15 to 30MPa and the menthol fraction of 0 to 5wt.%, the RESS process produced ultrafine Lynestrenol particles (from 58 to 326nm) from its original particles as reflected by SEM and zetasizer analysis.