Oral absorption improvement of poorly soluble drug using solid dispersion technique

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Medicinal Chemistry

Background:

• MFB-1041, a novel triazole antifungal, exhibits poor oral absorption and low aqueous solubility.
• Developing effective oral formulations is crucial for enhancing the therapeutic potential of poorly soluble drugs.

Purpose of the Study:

• To improve the oral absorption and solubility of MFB-1041.
• To evaluate solid dispersion systems for enhanced drug delivery.
• To investigate the impact of polymer type and preparation method on MFB-1041 bioavailability.

Main Methods:

• Preparation of solid dispersions using enteric polymers (HP-55, CMEC) and a nonenteric polymer (Metolose).
• Evaluation of drug solubility in alkaline media.
• Assessment of oral bioavailability in beagle dogs via suspension and solid dispersion formulations.
• Characterization of drug phase change using X-ray powder diffraction.
• Stability testing of the prepared solid dispersions.

Main Results:

• Solid dispersions significantly increased MFB-1041 solubility and oral bioavailability (over 6-fold higher than suspension).
• X-ray diffraction confirmed a complete phase transition from crystalline to amorphous state in solid dispersions.
• Spray-drying using enteric polymers yielded stable preparations with consistent absorption profiles.
• Enhanced solubility in alkaline media correlated with improved oral absorption.

Conclusions:

• Solid dispersion technology, particularly spray-drying with enteric polymers, effectively enhances MFB-1041 solubility and oral bioavailability.
• Amorphous drug state achieved through solid dispersion is key to improved absorption.
• The developed formulation offers a stable and effective oral delivery system for MFB-1041.