Effect of operating parameters on PVP/tadalafil solid dispersions prepared using supercritical anti-solvent process

• Tadalafil was applied to supercritical anti-solvent for the first time.
• We used Box–Behnken design to give general idea of how temperature, pressure and drug concentration affect on the particle formation.
• Increasing the drug concentration gives larger particle size and irregular shape of particle with partially in crystalline form.
• Increasing the density of anti-solvent produces smaller droplet of drug solution and give smaller primary particle to have higher and faster solubility of tadalafil solid dispersion.

Supercritical anti-solvent (SAS) process was employed to produce tadalafil solid dispersion sub-micron particles. Three independent variables for the SAS process (temperature, pressure, and drug concentration) were varied in order to investigate the effects on particle size and morphology of PVP/tadalafil solid dispersion (drug to polymer ratio 1:4). The mean particle size decreased with decreasing temperature (50 → 40 °C) and concentration (15 → 5 mg/mL) and increasing pressure (90 → 150 bar). Depending on the experimental variable, the mean particle size varied from 200 nm to 900 nm, and the dominant experimental variable was determined to be the drug concentration. Moreover, at a concentration of 15 mg/mL with any other process conditions, tadalafil tended to partially aggregate in crystalline form with irregular particle shapes. The results of in vitro dissolution experiments showed good correlation with mean particle size and crystallinity of the SAS-processed particles, in that the highest drug concentration showed the least dissolution rate and vice versa. Therefore, among the three variables studied, the drug concentration is the major factor that produces sub-micron particles in the SAS process.

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