Polymers' ultrafine particles for drug delivery systems precipitated by supercritical carbon dioxide + organic solvent mixtures

Abstract

The applicability of supercritical antisolvent precipitation (SAS) is restricted to hydrophobic substances because of the very limited solubility of water in CO2 at ordinary SAS operating conditions (40–60°C, 10–25MPa). To overcome this limitation, a technique has been developed, named expanded liquid antisolvent (ELAS), in which mixtures of supercritical carbon dioxide (scCO2) and organic solvents, at expanded liquid conditions, are used as the antisolvent: water solubility is widely enhanced.In this work, sodium alginate and polyvinyl alcohol (PVA), two water-soluble polymers, used as carrier for drug delivery systems, were successfully micronized by ELAS. Different antisolvent mixtures were used: scCO2+ethanol, scCO2+acetone and scCO2+isopropyl alcohol. Operating at 15MPa and 40°C, varying the organic co-antisolvent, the co-antisolvent mole fraction and the concentration of the polymer in the aqueous solution, nanoparticles (with a mean diameter of about 200nm), microparticles with smooth surface (with a mean diameter in the range of 0.9–12.5μm for sodium alginate and 2–9μm for PVA) and nanostructured microparticles (with a mean diameter of about 11μm) were produced. XRD analyses on the processed powders revealed that no modifications in the polymer structure were induced by ELAS processing. Solvent residue analyses revealed that the co-antisolvent residue ranged between 50 and 300ppm depending on the organic solvent used.