Use of solvent mixtures in supercritical antisolvent process to modify precipitates morphology: Cellulose acetate microparticles

•Use of solvent mixtures to produce microparticles.•Transition from two-phase to one-phase mixing regime.•Effect of pressure, concentration of the liquid solution and solvent mixtures on particle size and particle size distribution.

In the supercritical antisolvent precipitation (SAS), the jet fluid dynamics is characterized by two-phase mixing at subcritical conditions, and by one-phase mixing at completely developed supercritical conditions. The amplitude of the pressure range, in which binary systems organic solvent/scCO2 exhibit the transition between two-phase to one-phase mixing, depends on the organic solvent that is in contact with supercritical carbon dioxide (scCO2) and conditions the morphology of the microparticles produced by SAS. When this pressure range is wide, as in the case of dimethylsulfoxide (DMSO), solutes solubilized in the organic solvent can be precipitated as microparticles by atomization, droplets formation and drying; when this pressure range is narrow, as for acetone, gas mixing prevails and only nanoparticles are generally observed. Therefore, generally speaking, solutes that are soluble only in solvents exhibiting gas mixing in scCO2, do not exhibit microparticles morphology and this fact is a limitation for several industrial applications.In this work, a model compound, cellulose acetate (CA), that is slightly soluble in DMSO and freely soluble in acetone, was processed by SAS using mixtures of the two solvents that exhibit intermediate behaviors between the two pure solvents, to extend two phase mixing and produce CA microparticles. Using different DMSO/acetone mixture percentages, the effects of the polymer concentration in the liquid solution and of the pressure were studied. A mixture of DMSO/Acetone 50/50 (v/v), at a pressure of 85 bar and a concentration of the liquid solution equal to 40 mg/mL, efficiently produced non-coalescing CA microparticles with a mean diameter of 0.42 μm and a standard deviation of about 0.15 μm, demonstrating that this SAS strategy can be successful.

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