Bioavailability improvement by atomic layer coating: Fenofibrate a case study

Balaji Ganapathy

doi:10.1016/j.xphs.2024.10.052

Bioavailability improvement by atomic layer coating: Fenofibrate a case study

2025-01-01

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DOI：10.1016/j.xphs.2024.10.052

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Biopharmaceutical Classification Systems (BCS) class II drugs show poor solubility and high permeability in the body. Fenofibrate (FF) is a classic example of a BCS class II drug, used to treat high cholesterol and triglyceride (fat-like substances) levels in the blood. Atomic layer coating (ALC) is a surface engineering technology adapted from the semiconductor industry, where metal oxides are coated one atomic layer at a time over the active pharmaceutical ingredients (API) particles. ALC coating was proven to improve the processability, alter the hydrophilicity, improve the stability, and fine-tune the release of drugs. Herein, we report the intervention of ALC coating in enhancing the bioavailability of a poorly water-soluble drug (fenofibrate) in the animal model. The physical properties of uncoated fenofibrate were compared with those of zinc oxide-coated and silicon oxide-coated fenofibrate. Following the application of the coatings, the structural integrity (both chemical stability and solid-state stability) of the active pharmaceutical ingredient (API) remained uncompromised, as corroborated by 1H NMR and powder X-ray diffraction analyses. Notably, zinc oxide-coated fenofibrate exhibited favorable flow characteristics, whereas no discernible enhancement in flow behavior was observed for silicon oxide-coated fenofibrate. The results from contact angle measurements suggest that the silicon oxide-coated fenofibrate exhibits superior wetting behavior, as indicated by a contact angle nearing 0 degrees. The application of ALC demonstrates an enhanced dissolution rate when compared to the uncoated active pharmaceutical ingredient (API) while leaving its equilibrium solubility unaffected. Coating the API with silicon oxide improves particle hydrophilicity and wetting properties, whereas zinc oxide coating aids in particle de-agglomeration, thereby enhancing their interaction with an aqueous medium. In vivo bioavailability studies conducted on rodents and larger animal (dog) models indicate a substantial increase in bioavailability (approximately 2 times) for the silicon oxide-coated API in comparison to the uncoated API, as determined by the area under the curve (AUC). Furthermore, the Cmax values for the silicon oxide-coated API also demonstrate a significant increase (approximately 3 times) over the uncoated API. Notably, an oral subacute toxicity study of ALC silicon-coated fenofibrate revealed no toxic effects attributable to the coating. This study underscores the potential of ALC in augmenting the bioavailability of BCS(II) drugs. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Keyword:

Dispersibility

Wettability

Dissolution studies

Atomic layer deposition

Zinc oxide coating

Silicon oxide coating

Bioavailability improvement by atomic layer coating: Fenofibrate a case study

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