A Syloid-stabilized solid lipid dispersion platform for fast-onset fenofibrate delivery: a rational docking-driven design strategy

Hyperlipidemia, characterized by elevated lipid levels carries an increased risk of cardiovascular disease, which requires rapid and effective lipid-lowering therapy. Fenofibrate (BCS class II) is a potent anti-lipemic agent, but its poor water solubility hinders its efficacy due to reduced bioavailability. This study investigates a rational docking-guided formulation strategy to develop immediate-release fenofibrate tablets using a solid lipid dispersion to enhance its dissolution rate and oral bioavailability. Molecular docking was employed to understand the intermolecular affinity between fenofibrate and lipidic excipients, Acconon C-44 and Acconon MC8-2 – were identified as optimal carriers due to their strong hydrophobic interactions with the drug, suggesting enhanced molecular stabilization and solubility enhancement. The binary lipid mixture exhibited a synergistic solubilization effect, enabling partial amorphization of the drug via hot-melt granulation, as confirmed by XRD and DSC analyses. Factorial design analysis showed a direct relationship between lipid–adsorbent ratio and dissolution enhancement, achieving 97.98 ± 0.263% release within 60 minutes, nearly 2-fold faster than marketed fenofibrate tablets. The improved compressibility and flow properties further verified suitability for industrial-scale tablet manufacture. This study establishes a predictive and translational biopharmaceutics platform that integrates in-silico excipient selection with amorphous lipid dispersion engineering to deliver fast-onset therapy for hyperlipidemia and other BCS class II/IV drugs.