Effect of the modifier on the particle formation and crystallisation behaviour during precipitation from aqueous solutions

Ethanol is a commonly added modifier to supercritical CO₂ for particle formation from aqueous solutions. Four modifiers - methanol, ethanol, 2-propanol and acetone - were studied to determine the extent of the effect of the modifier selection on the particles produced and to determine more precisely the precipitation mechanisms. The strong anti-solvent effect of methanol on the solute was shown by the production of metastable β-glycine, phenylalanine anhydrate and lysozyme agglomerated nanoparticles. Ethanol showed such an anti-solvent effect only when use at higher fraction in the supercritical phase, followed by 2-propanol and acetone. 2-Propanol and acetone mainly contributed to the precipitation of the solute by increasing the solubility of the water in the supercritical phase. In such precipitation conditions the more stable α-glycine, phenylalanine monohydrate and lysozyme microspheres were produced by the evaporation of the solution into the CO₂ phase. The putative anti-solvent effect of CO₂ in the systems studied was not clearly observed, but it remains that CO₂ is essential to the SCF-drying process.