Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

Abstract

Purpose The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Methods Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil ® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. Results All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of <200 nm with the drug present in the amorphous state. It demonstrated the highest solubility (32.51±2.41 μg/mL), an excellent dissolution (~85% in 10 minutes), and an oral bioavailability ~2.5-fold better than that of the free drug. It showed similar oral bioavailability compared to the conventional solid dispersion. Conclusion Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate.

<p>Electrosprayed Polymeric Nanospheres for Enhanced Solubility, Dissolution Rate, Oral Bioavailability and Antihyperlipidemic Activity of Bezafibrate</p>

“…This enhancement in solubility might be ascribed to increased wetting of bezafibrate by the hydrophilic polymer. 24 Moreover, as the quantity of PVP K30 increased further in formulations V-VII, an apparent decrease in solubility was observed. However, the solubility results were not significantly different (p > 0.05) from one another in these formulations.…”

“…A pharmaceutical nanoparticle is a drug-loaded object possessing a diameter of not more than 1000 nm. 24 From Figure 5B, it can be appraised that the average particle-size of the formulation was not more than 500 nm. Thus, particles of electrosprayed ternary solid dispersion formulation V were nano-sized particles.…”

“…30,31 Nano-sized solid dispersion is a magnificent drug delivery system to ameliorate dissolution rate and solubility of a poorly water-soluble substance in the aqueous media. 18 with electrospraying is a smart way to fabricate nanoparticulated solid dispersions; 24,35 accordingly, in the present research work we adopted these techniques to obtain bezafibrate-loaded nanoparticulated solid dispersions (nanospheres). The recipe of each formulation is shown in Table 1.…”

“…The solvent-evaporation method and the electrospraying technique were employed for the preparation of solid dispersions. 24 The composition of trialed formulations is shown in Table 1. For each formulation, bezafibrate powder was completely dissolved in ethanol.…”

“…Electrospraying is a promising technique that can produce drug-loaded spherical nanoparticles. 18,20 Electrospraying has been elegantly performing in the fabrication of polymeric nanoparticles loaded with antibiotics, [21][22][23] fibrates, 24 anti-inflammatory drugs 25,26 and hormones. [27][28][29] A pharmaceutical nanoparticle is a drug-laden vehicle bearing a dimension of <1000 nm.…”