Itraconazole Formation Using Supercritical Carbon Dioxide

Abstract

A new method of preparing Itraconazole (C₃₅H₃₈Cl₂N₈O₄), a synthetic triazole antifungal agent, was developed using supercritical carbon dioxide (SC CO₂) while eliminating the use of toxic solvents. Dissolution amounts of the product were measured in gastric fluid and compared to those of conventional drug formulations. Different operating conditions (five levels of treatment temperature ranging between 110–140°C, four levels of treatment pressure ranging between 30–400 atm, and four different treatment times ranging from 10–60 minutes) were tested in order to produce a desired Itraconazole product, which does not degrade during the product formation and has the highest extent of dissolution in gastric fluid after one hour. Itraconazole dissolution of 100% at one‐hour was achieved for the drug produced at the optimum treatment condition: 135°C, 300 atm, and 30 minutes. Extent of dissolution obtained from this solvent and detergent‐free process is 10% higher than that of the conventional method involving toxic organic solvents. Itraconazole produced using SC CO₂ should provide minimal side effects in human body.

Key Words:

• Supercritical fluids
• CO₂
• Itraconazole
• Dissolution rate