Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Itraconazole (ITZ) bioavailability is limited by its poor solubility.
• Solid dispersions are a strategy to enhance the solubility and bioavailability of poorly soluble drugs.
• Cellulose acetate phthalate (CAP) and polyvinyl acetate phthalate (PVAP) are potential concentration-enhancing polymers for drug formulations.

Purpose of the Study:

• To produce amorphous engineered particle compositions of itraconazole (ITZ) with CAP and PVAP.
• To investigate the effect of these polymers on the bioavailability of ITZ solid dispersions.
• To evaluate the in vitro and in vivo performance of ITZ-polymer formulations.

Main Methods:

• Amorphous solid dispersions were prepared using ultra-rapid freezing.
• Characterization included X-ray diffraction, modulated differential scanning calorimetry, energy dispersive spectroscopy, and scanning electron microscopy.
• In vitro dissolution studies were performed in acidic and neutral media, followed by in vivo pharmacokinetic studies in rats.

Main Results:

• Engineered particles exhibited amorphous structures with significantly increased surface areas compared to micronized ITZ.
• ITZ:CAP formulations showed superior supersaturation in neutral media and improved in vitro performance.
• In vivo studies demonstrated a significant improvement in oral bioavailability (p < 0.05) and enhanced intestinal targeting with the 1:2 ITZ:CAP formulation.

Conclusions:

• Amorphous ITZ compositions with enteric concentration-enhancing polymers (CAP) significantly improve oral bioavailability.
• Enhanced intestinal targeting and prolonged supersaturation contribute to the improved drug delivery.
• The stabilization mechanism is attributed to drug-polymer interactions, including steric hindrance and hydrogen bonding.