The study aimed to enhance the oral bioavailability of Febuxostat (FBX), a Biopharmaceutics Classification System (BCS) class II drug used for treating gout and hyperuricemia. This objective was achieved by formulating FBX-loaded solid lipid nanoparticles (SLNs) using a modified hot homogenization method followed by sonication. The formulation parameters, including lipid concentration, surfactant concentration, and co-surfactant amount, were systematically optimized using a Box-Behnken design. Afterward, the optimized FBX-SLNs were extensively characterized using advanced techniques. Key properties included a mean particle size of 200 nm, a narrow size distribution with a polydispersity index (PDI) of 0.2 ± 0.07, a zeta potential of − 22.2 ± 0.2 mV, and an encapsulation efficiency (EE %) of 80 ± 1.2%. Transmission electron microscopy (TEM) revealed a spherical morphology, while Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD) confirmed the absence of chemical interactions between the drug and excipients and the transformation of FBX into an amorphous form. Differential scanning calorimetry (DSC) further corroborated the reduction in FBX crystallinity through changes in the thermal behavior of the formulation. Additionally, in vitro drug release studies demonstrated a sustained release profile at relevant pH levels, highlighting the potential of FBX-SLNs for controlled delivery. In vivo, pharmacokinetic evaluations showed significant enhancement in FBX bioavailability, with an area under the curve (AUC₀–∞) of 361.04 mgh/mL and a peak plasma concentration (Cmax) of 5.3583 μg/mL for FBX-SLNs compared to the pure drug solution. These findings indicate that FBX-SLNs represent a promising strategy for improving the oral bioavailability of FBX, offering a superior alternative to conventional therapy. Graphical Abstract Visual representation of the processes involved in increasing the oral bioavailability of FBX through the use of SLNs. A Surface-bound SLN absorption in the intestines. B Internalization of SLNs via endocytosis. C SLN adhesion resulting in drug uptake via Peyer’s patches in the presence of M cells. D Passive diffusion by micellar solubilization and the creation of chylomicrons. E Excipient inhibition of efflux transporters. F Characterization and pharmacokinetics

Nanocarrier-Based Approach: Solid Lipid Nanoparticles for the Enhanced Bioavailability of Febuxostat

期刊论文
发表日期：

2025年3月20日

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Shehram Qazafi,
Danish Mazhar,
Dur E Nayab,
Hussain Ali,
Salman Khan,
Saeed Ahmad Khan

摘要

The study aimed to enhance the oral bioavailability of Febuxostat (FBX), a Biopharmaceutics Classification System (BCS) class II drug used for treating gout and hyperuricemia. This objective was achieved by formulating FBX-loaded solid lipid nanoparticles (SLNs) using a modified hot homogenization method followed by sonication. The formulation parameters, including lipid concentration, surfactant concentration, and co-surfactant amount, were systematically optimized using a Box-Behnken design. Afterward, the optimized FBX-SLNs were extensively characterized using advanced techniques. Key properties included a mean particle size of 200 nm, a narrow size distribution with a polydispersity index (PDI) of 0.2 ± 0.07, a zeta potential of − 22.2 ± 0.2 mV, and an encapsulation efficiency (EE %) of 80 ± 1.2%. Transmission electron microscopy (TEM) revealed a spherical morphology, while Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD) confirmed the absence of chemical interactions between the drug and excipients and the transformation of FBX into an amorphous form. Differential scanning calorimetry (DSC) further corroborated the reduction in FBX crystallinity through changes in the thermal behavior of the formulation. Additionally, in vitro drug release studies demonstrated a sustained release profile at relevant pH levels, highlighting the potential of FBX-SLNs for controlled delivery. In vivo, pharmacokinetic evaluations showed significant enhancement in FBX bioavailability, with an area under the curve (AUC₀–∞) of 361.04 mgh/mL and a peak plasma concentration (C_max) of 5.3583 μg/mL for FBX-SLNs compared to the pure drug solution. These findings indicate that FBX-SLNs represent a promising strategy for improving the oral bioavailability of FBX, offering a superior alternative to conventional therapy.

Graphical Abstract

Visual representation of the processes involved in increasing the oral bioavailability of FBX through the use of SLNs. A Surface-bound SLN absorption in the intestines. B Internalization of SLNs via endocytosis. C SLN adhesion resulting in drug uptake via Peyer’s patches in the presence of M cells. D Passive diffusion by micellar solubilization and the creation of chylomicrons. E Excipient inhibition of efflux transporters. F Characterization and pharmacokinetics