Bioavailability improvement by atomic layer coating: Fenofibrate a case study

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Biopharmaceutical Classification Systems (BCS) class II drugs exhibit poor solubility and high permeability.
• Fenofibrate (FF), a BCS class II drug, is used to manage high cholesterol and triglyceride levels.
• Atomic layer coating (ALC) is a surface engineering technique for modifying active pharmaceutical ingredient (API) particles.

Purpose of the Study:

• To investigate the efficacy of ALC in enhancing the bioavailability of fenofibrate.
• To compare the physical and performance characteristics of uncoated, zinc oxide-coated, and silicon oxide-coated fenofibrate.
• To assess the in vivo safety and efficacy of ALC-modified fenofibrate.

Main Methods:

• Fenofibrate particles were coated using ALC with silicon oxide and zinc oxide.
• Physical properties (flow, wetting) and chemical/solid-state stability (1H NMR, powder X-ray diffraction) were analyzed.
• In vivo studies in rodents and dogs evaluated bioavailability (AUC, Cmax).
• Oral subacute toxicity studies were conducted on silicon oxide-coated fenofibrate.

Main Results:

• ALC coatings (silicon oxide, zinc oxide) did not compromise the structural integrity of fenofibrate.
• Silicon oxide coating improved wetting (contact angle near 0°) and hydrophilicity.
• Zinc oxide coating improved flow characteristics and particle de-agglomeration.
• ALC enhanced dissolution rates without altering equilibrium solubility.
• In vivo studies showed a ~2-fold increase in AUC and ~3-fold increase in Cmax for silicon oxide-coated fenofibrate.
• No toxicity was observed for ALC silicon-coated fenofibrate.

Conclusions:

• ALC is a promising technology for improving the bioavailability of poorly water-soluble BCS class II drugs like fenofibrate.
• Silicon oxide coating enhances fenofibrate bioavailability through improved wetting and hydrophilicity.
• Zinc oxide coating offers benefits in particle processing and dispersion.
• ALC-modified fenofibrate demonstrates a favorable safety profile.