Dissolution-microdialysis predicts oral bioavailability from phospholipid-based amorphous solid dispersions.

Area of Science:

• Pharmaceutics
• Drug Delivery
• Physical Pharmacy

Background:

• Amorphous solid dispersions (ASDs) enhance the solubility of poorly soluble drugs.
• Phospholipid-based ASDs are a promising formulation strategy.
• Understanding drug release mechanisms is crucial for predicting in vivo performance.

Purpose of the Study:

• To evaluate aprepitant dissolution from phospholipid-based ASDs under various conditions.
• To compare conventional sampling with microdialysis for assessing supersaturation.
• To establish an in vitro-in vivo correlation (IVIVC) for oral bioavailability prediction.

Main Methods:

• Preparation and characterization of binary and ternary ASDs containing aprepitant.
• Dissolution testing in simulated intestinal fluid with and without lipolysis (pancreatin).
• Simultaneous sampling using centrifugation and microdialysis.
• Solid-state analysis via X-ray powder diffraction (XRPD).

Main Results:

• Ternary and binary natural phospholipid ASDs were amorphous; binary hydrogenated phospholipid ASD showed some crystallinity.
• Lipolysis did not affect drug release from the natural phospholipid ASD.
• Microdialysis revealed a 'spring and parachute' effect, with higher supersaturation in the ternary ASD.
• IVIVC based on molecularly dissolved drug was superior, achieving R² values up to 0.9712.

Conclusions:

• Microdialysis provides mechanistic insights into drug release and supersaturation.
• Aprepitant ASDs demonstrate significant supersaturation, particularly the ternary formulation.
• Dissolution studies using microdialysis sampling offer excellent prediction of oral bioavailability.