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

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 10 μm as a drug material were dissolved in supercritical CO2 and then expanded rapidly through a nozzle with 0.6 mm 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 30 MPa and the menthol fraction of 0 to 5 wt.%, the RESS process produced ultrafine Lynestrenol particles (from 58 to 326 nm) from its original particles as reflected by SEM and zetasizer analysis.

Graphical abstractRESS process was implemented for reduction of Lynestrenol powder from 10 μm average size to nanosized particles. Effect of temperature, pressure and co-solvent and their interactions were simultaneously analyzed by factorial design experiments. The average size of the particles in different experiments was observed in the range of 58 to 326 nm.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Formation of medical nanoparticles by Rapid expansion Supercritical CO2 Solution. ► Nanopowder formation of Lynestrenol from 10 μm to lower than 100 nm ► Study the effect of pre-expansion temperature, pressure and menthol fraction ► Statistical experimental design by factorial method