Production and characterization of ultrafine aspirin particles by rapid expansion of supercritical solution with solid co-solvent (RESS-SC): expansion parameters effects

Abstract

Micronization of polar drugs by the rapid expansion of supercritical solution (RESS) process is not successful in near critical pressure due to the extremely low solubility of the drugs in near-critical CO₂. In this study, for the first time, micronization of aspirin was successfully performed by the rapid expansion of supercritical solution with solid co-solvent (RESS-SC) process in near-critical pressure by using menthol as solid co-solvent. To achieve this aim, some experiments were conducted to study the influences of expansion pressure ranging from 1 to 8 bar, pre-expansion temperature ranging from 30 to 70 °C, spray distance ranging from 2 to 6 cm, nozzle diameter ranging from 300 to 700 µm, and nozzle types (orifice - capillary) on the morphology and size of aspirin particles. The obtained particles were characterized by x-ray diffraction (XRD) and scanning electron microscope (SEM) analysis. Utilizing RESS-SC process in near-critical condition, aspirin particles in the range of 0.17–6.61 µm were obtained.

Keywords:

• RESS
• solid co-solvent
• aspirin
• nanoparticles
• menthol
• CO₂