Supercritical Assisted Atomization: effect of operative conditions on Polyvinylpyrrolidone microparticle size and morphology

Polyvinylpyrrolidone (PVP) is an hydrophilic polymer approved by U.S. Food and Drug Administration for medical and pharmaceutical applications and it is generally regarded as safe. Polyvinylpyrrolidone could be used to increase the dissolution rate of many hydrophobic drugs and is an inhibitor of recrystallization.

 Traditional micronization processes, such as spray drying and spray freeze drying, show some limitations: high solvent residues and long processing times. Supercritical fluid based micronization technologies represent possible alternatives to the traditional micronization processes taking advantage of the hybrid gas-like and liquid-like properties of supercritical CO₂ (SC- CO₂) to obtain a better modulation of the particle size and lower solvent residues.

Supercritical assisted atomization (SAA) is an efficient technique to produce microparticles and coprecipitates of several compounds: active molecules, proteins and polymers. This process uses SC-CO₂ as a co-solute in the solution containing the compound to be micronized. The dissolution of SC-CO₂ in the liquid feed is a key parameter to reduce viscosity and surface tension of the resulting mixture, thus improving the micronization mechanism.

In this work, Polyvinylpyrrolidone has been successfully micronized using SAA, obtaining a good control of the particle size in micrometric and sub-micrometric ranges, using different kind of solvents: ethanol, water, and mixture water-acetone. The smallest Polyvinylpyrrolidone particles produced in this study showed a mean diameter of  about 0.5 μm and a standard deviation of 0.2 μm. Polyvinylpyrrolidone particles produced in this work can be efficiently used as carrier for drugs when specific particle size is requested, since changing liquid solvent and process operating conditions it is possible to modulate the particle size distribution.