Particle design is becoming one of the main features in the production of pharmaceuticals, food, cosmetics and other specialty chemical products. With optimized drug particle attributes (particle size, size distribution and particle morphology), improved drug targeting, controlled drug release, solubility and bioavailability can be achieved. The application of supercritical fluid processing in pharmaceutical research is increasing particularly in the field of particle formation for drug delivery systems, mainly due to advantages over the conventional particle formation in terms of improved control, flexibility, ease of operation and level of toxicity from the presence of organic solvents and contaminants.

Particle formation of salicylic acid using supercritical carbon dioxide (CO₂) was investigated using the Precipitation with Compressed Anti-solvent (PCA) technique using ethanol and acetone as solvents. The solubility of salicylic acid (SA) in supercritical CO₂ was measured in its pure form and with modifiers, at 45°C and 55°C over a pressure range of 95 to 250 bar. The output of the study gave promising conditions in particle formation by adjusting parameters based on the phase diagram obtained. Particles in the nano-range can be produced in the higher supersaturation region without changing the nozzle size of the PCA system. All the experimental conditions investigated here gave an average particle size of approximately 100 nm, with the smallest average particle size of 63.35 nm by using 1% acetone modifying condition at 45°C. The largest average particle size produced was 102.75 nm at condition with 1% ethanol operating under temperature of 55°C. A dissolution experiment was also carried out to show significant improvement of drug dissolution rate with the smaller particle size.