Optimization of a PGSS (particles from gas saturated solutions) process for a fenofibrate lipid-based solid...

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Fenofibrate's oral bioavailability is limited by its poor solubility.
• Solid dispersions can enhance the dissolution of poorly soluble drugs.
• The Particles from Gas Saturated Solutions (PGSS) process offers potential for solid dispersion manufacturing.

Purpose of the Study:

• To develop a fenofibrate-loaded solid dispersion formulation using the PGSS process.
• To optimize PGSS process parameters for improved fenofibrate dissolution and oral bioavailability.

Main Methods:

• Utilized the Particles from Gas Saturated Solutions (PGSS) process for solid dispersion preparation.
• Employed a biphasic dissolution test to evaluate in vitro drug release.
• Applied a design of experiments (DOE) approach, including screening and central composite designs, to optimize PGSS parameters.

Main Results:

• Identified key PGSS parameters influencing fenofibrate dissolution: drug loading, autoclave temperature and pressure, connection temperature, and nozzle diameter.
• Optimized process conditions to maximize fenofibrate release into the organic phase.
• Validated the statistical models by demonstrating close agreement between measured and predicted dissolution profiles.

Conclusions:

• The PGSS process is a viable method for producing fenofibrate solid dispersions with enhanced dissolution.
• Optimization of PGSS parameters, guided by DOE and in vitro dissolution testing, is crucial for improving fenofibrate oral bioavailability.
• The developed formulation and optimized process show promise for enhancing the therapeutic efficacy of fenofibrate.