Exploring Nanonization Strategies for Enhancing the Performance of Fenofibrate API in Lipid-Lowering Therapy

Fenofibrate is a widely prescribed lipid-lowering agent for hyperlipidemia and mixed dyslipidemia. Despite its effectiveness, fenofibrate’s very low water solubility (BCS Class II) limits its oral bioavailability. To overcome this, the pharmaceutical industry has turned to nanonization—reducing drug particles to the nanometer scale—to improve solubility and systemic absorption.

1. Importance of Nanonization for Fenofibrate

Fenofibrate acts as a prodrug, converting in vivo to fenofibric acid, its active form. Poor aqueous solubility causes slow dissolution and variable absorption, leading to inconsistent drug levels. Nanonization aims to:

• Increase dissolution rate by enlarging surface area

• Enhance oral bioavailability

• Reduce food dependency for absorption

• Provide consistent plasma drug concentrations

2. Key Nanonization Techniques

• Wet Media Milling (Top-Down): Mechanical size reduction with milling beads to create nanocrystals (<500 nm). Scalable and widely accepted.

• High-Pressure Homogenization: Uses high shear forces in stabilizing media; ideal for heat-sensitive drugs, producing stable nanosuspensions.

• Antisolvent Precipitation (Bottom-Up): Rapid mixing of drug solution with aqueous antisolvent controls particle nucleation; often combined with surfactants or polymers.

• Spray Drying: Converts nanosuspensions into solid nanoparticles for use in fast-dissolving tablets or granules.

3. Formulation and Stability Factors

Successful fenofibrate nanonization requires optimizing:

• Stabilizers: Surfactants (e.g., SDS, Poloxamer 188) and polymers (e.g., HPMC) to prevent aggregation.

• Solid State: Control over amorphous vs crystalline forms affects stability and dissolution.

• Redispersibility: Maintaining nanoparticle size upon dispersion in GI fluids is crucial.

• Packaging: Use of moisture and oxygen barrier materials protects product integrity.

4. Market Examples and Regulatory Considerations

Nanotechnology-based fenofibrate products include:

• Tricor® (micronized form)

• Trilipix® / Antara® (nanocrystal formulations with improved bioavailability and reduced food effect)

Regulators like FDA and EMA recognize nanonized formulations but require detailed particle characterization, stability data, and in vitro–in vivo correlation (IVIVC).

Conclusion

Nanonization is a proven, effective strategy to overcome fenofibrate’s solubility challenges, improving dissolution and bioavailability. With continued advances in particle engineering and formulation, nanonized fenofibrate represents a key innovation in lipid-lowering therapies and sets a benchmark for poorly soluble drug development.