Novel ezetimibe-loaded fibrous microparticles for enhanced solubility and oral bioavailability by electrospray technique

Abstract

This study developed a novel electrospray-based fibrous microparticle for increased water solubility and enhanced oral bioavailability of a poorly water-soluble drug, ezetimibe. Ezetimibe-loaded fibrous microparticles were prepared by an electrospray technique using polyvinylpyrrolidone (PVP) and Cremophor RH40 as carriers. Nine different formulations were prepared with varying ratios of the drug and carrier. These were then evaluated for water solubility and dissolution. The formation of ezetimibe-loaded fibrous microparticles was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), particle size measurement, and scanning electron microscopy (SEM) analyses. Pharmacokinetic evaluation of the optimized ezetimibe-loaded fibrous microparticles was conducted in rats and compared with that of the drug alone. All of the electrospray-based fibrous microparticles had significantly improved water solubility and dissolution compared to the drug. An optimized ezetimibe-loaded fibrous microparticle composed of ezetimibe/PVP/Cremophor RH40 at 1/5/0.1 (w/w) had 26.3- and 4.6-fold higher solubility and dissolution, respectively, than ezetimibe powder. Solid state characterization showed that ezetimibe exists in the amorphous state within the fibrous microparticles and exhibits smaller particles (less than 20 μm) as compared to the ezetimibe powder. For electrospray-based fibrous microparticles, the in vivo pharmacokinetic parameters AUC and Cmax were 2.1- and 2.6-fold higher, respectively, than those of the ezetimibe powder. The results of this study showed that electrospray-based fibrous microparticles could improve water solubility and bioavailability, which provides a novel approach for the poorly water-soluble ezetimibe.