Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

Abstract

Background The intention of this research was to prepare and compare various solubility-enhancing nanoparticulated systems in order to select a nanoparticulated formulation with the most improved oral bioavailability of poorly water-soluble fenofibrate. Methods The most appropriate excipients for different nanoparticulated preparations were selected by determining the drug solubility in 1% (w/v) aqueous solutions of each carrier. The polyvinylpyrrolidone (PVP) nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanocorpuscles, and gelatin nanocapsules were formulated as fenofibrate/PVP/sodium lauryl sulfate (SLS), fenofibrate/HP-β-CD, and fenofibrate/gelatin at the optimized weight ratios of 2.5:4.5:1, 1:4, and 1:8, respectively. The three solid-state products were achieved using the solvent-evaporation method through the spray-drying technique. The physicochemical characterization of these nanoparticles was accomplished by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Their physicochemical properties, aqueous solubility, dissolution rate, and pharmacokinetics in rats were investigated in comparison with the drug powder. Results Among the tested carriers, PVP, HP-β-CD, gelatin, and SLS showed better solubility and were selected as the most appropriate constituents for various nanoparticulated systems. All of the formulations significantly improved the aqueous solubility, dissolution rate, and oral bioavailability of fenofibrate compared to the drug powder. The drug was present in the amorphous form in HP-β-CD nanocorpuscles; however, in other formulations, it existed in the crystalline state with a reduced intensity. The aqueous solubility and dissolution rates of the nanoparticles (after 30 minutes) were not significantly different from one another. Among the nanoparticulated systems tested in this study, the initial dissolution rates (up to 10 minutes) were higher with the PVP nanospheres and HP-β-CD nanocorpuscles; however, neither of them resulted in the highest oral bioavailability. Irrespective of relatively retarded dissolution rate, gelatin nanocapsules showed the highest apparent aqueous solubility and furnished the most improved oral bioavailability of the drug (~5.5-fold), owing to better wetting and diminution in crystallinity. Conclusion Fenofibrate-loaded gelatin nanocapsules prepared using the solvent-evaporation method through the spray-drying technique could be a potential oral pharmaceutical product for administering the poorly water-soluble fenofibrate with an enhanced bioavailability.

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

“…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.…”

“…As compared A B with bezafibrate plain powder, bioavailability was~5.5-fold with electrosprayed ternary solid dispersion formulation V. The improved bioavailability might be ascribed to amelioration in the aqueous solubility and dissolution of bezafibrate resulting from improved wetting due to hydrophilic polymer, particle-size diminution and alteration of the crystalline form of the drug to its amorphous counterpart. 18 The mean values of TG, HDL, LDL and TC are shown in Figure 8. The negative control gave values 50.17 ± 12.25, 33.17 ± 7.98, 13.00 ± 3.85 and 55.87 ± 11.01 mg/ dL, respectively ( Figure 8A).…”

“…17 Improvement in solubility and dissolution by the solvent-evaporated solid dispersion is usually a consequence of conversion of the crystalline form of the drug into its amorphous counterpart. 18 Polymeric matrices present in this drug delivery system inhibit recrystallization of the drug during evaporation process. 19 There are several sophisticated ways to evaporate the solution, for instance, tray-drying, spray-drying, electrospraying, lyophilisation, supercritical fluid technique and so on.…”

“…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.…”

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

“…To overcome this limitation, large number of investigations had been conducted. Some reported approaches are development of self-microemulsifying drug delivery system [11] [12], impregnation of drug into various silica [13] [14] [15], impact of fillers [16], oral push-pull osmotic pump [17], electrosprayed nanospherules [18], nanosuspension [19], solid dispersion [10] [20] [21], nanoparticles formations [22], anti-solvent precipitation technique [23], a pair of side by side diffusion cells [24], holt-melt extrusion [25], core shell dual mesoporous silica nanoparticles [28], nanocomposites [26] [27], dry suspension and dry emulsion [28], controlled release matrix [29], lipidic dispersion [30] and co-crystals formation [31]. Among these physi- Although many SD approaches using various carriers have been examined, but there is no report regarding the use of blend of silica and PEG on dissolution property of FF.…”