Characterization and Pharmacokinetic Study of Aprepitant Solid Dispersions with Soluplus®

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Poorly water-soluble drugs present challenges in achieving adequate bioavailability.
• Solid dispersions are a key strategy to overcome poor solubility and enhance drug dissolution.
• Aprepitant, a poorly water-soluble drug, requires formulation optimization for improved therapeutic outcomes.

Purpose of the Study:

• To enhance the physicochemical properties and oral bioavailability of aprepitant using solid dispersions.
• To investigate the solid-state characteristics and dissolution behavior of aprepitant-loaded solid dispersions.

Main Methods:

• Preparation of aprepitant solid dispersions using various techniques.
• Characterization via dissolution testing, Fourier Transform Infrared (FTIR) spectroscopy, X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM).
• Pharmacokinetic evaluation in rat models to assess in vivo drug absorption.

Main Results:

• Solid dispersions markedly increased the dissolution rate of aprepitant, achieving nearly a five-fold improvement.
• XRPD, DSC, and SEM confirmed the amorphous state of aprepitant within the solid dispersions.
• FTIR indicated intermolecular hydrogen bonding between aprepitant and the polymer carrier.
• Pharmacokinetic studies showed a 2.4-fold increase in AUC0-t for solid dispersions compared to pure aprepitant, with comparable absorption to Emend®.

Conclusions:

• Aprepitant exists in an amorphous state within the prepared solid dispersions.
• Solid dispersions significantly improve the dissolution rate and oral bioavailability of aprepitant.
• The developed method is simple and effective for enhancing the delivery of poorly water-soluble drugs.