Ezetimibe Oral Solid Lipid Nanoparticle by Effervescent Dispersion Method: in Vitro Characterization And in Vivo Pharmacokinetic Study in Rats.

Abstract

Ezetimibe (EZT) is a class II drug of the Biopharmaceutics classification system (BCS), with limited aqueous solubility and high permeability. This study aims to enhance the solubility and oral bioavailability of EZT by developing EZT solid lipid nanoparticles (SLNs). EZT-SLNs were developed through the effervescent dispersion technique. Different amounts of Tween-80, Compritol ATO 888, and mannitol as cryoprotectant were used. F11 was the optimum formula with 154 nm in size and 90.26% entrapment efficiency. It demonstrates significant enhancements in solubility across various pH values. In addition, F11 shows a significantly higher drug release than pure EZT at all time points, and that's related to the reduction in the particle size and increasing its surface area along with the transformation from a crystalline state to an amorphous state. The powder X-ray diffraction and Differential Scanning Calorimetry tests confirmed this conversion from crystalline form to amorphous. The in vivo animal study demonstrated that the C_max and ${\text{ AUC}}_0^{\text{∞ }}$ of the EZT-SLNs group were significantly higher than the pure EZT group, after oral administration. In conclusion, EZT-SLNs with enhanced in vitro and in vivo properties were successfully developed using the effervescent dispersion technique.