Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Itraconazole, an antifungal agent, suffers from poor aqueous solubility, limiting its oral bioavailability.
• Solid dispersions are a promising strategy to enhance the dissolution and bioavailability of poorly soluble drugs.

Purpose of the Study:

• To prepare and characterize amorphous solid dispersions of itraconazole using co-spray-drying with Aerosil200.
• To evaluate the dissolution performance and stability of these solid dispersions.
• To assess the in vivo oral bioavailability of the optimized itraconazole solid dispersion.

Main Methods:

• Co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil200 at various weight ratios (50/50, 30/70, 40/60, 20/80).
• Characterization using X-ray powder diffraction (XRPD), solid-state NMR (SSNMR), and differential scanning calorimetry (DSC).
• Dissolution testing and in vivo oral bioavailability studies in rats.

Main Results:

• Amorphous itraconazole solid dispersions were successfully prepared, confirmed by XRPD, SSNMR, and DSC.
• Dissolution rates were enhanced compared to crystalline and glassy itraconazole.
• The 30/70 itraconazole/Aerosil200 dispersion demonstrated significantly enhanced oral bioavailability in rats compared to the crystalline drug.
• Stability studies showed varying degrees of crystallization upon storage, impacting dissolution performance.

Conclusions:

• Co-spray-drying is an effective method for producing amorphous itraconazole solid dispersions with Aerosil200.
• The 30/70 dispersion offers a promising formulation for improved itraconazole oral delivery.
• Further investigation into the adsorption mechanism onto Aerosil200 may optimize long-term dissolution stability.