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Enhanced solubility and oral bioavailability of poorly water-soluble fenofibrate via various polymeric nanoparticulated systems

Enhanced solubility and oral bioavailability of poorly water-soluble fenofibrate via various polymeric nanoparticulated systems
Han-Gon Choi
Issue Date
The intent of the present investigation was to formulate and compare different solubility-ameliorating nanoparticulated formulations so as to recognize a nanoparticulated preparation with the best enhanced oral bioavailability of hydrophobic fenofibrate. The best suitable hydrophilic carriers for various nanoparticulated systems were designated by scrutinizing the drug solubility in 1% (w/v) aqueous solutions of each excipient. The polyvinylpyrrolidone (PVP) nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanocorpuscles and gelatin nanocapsules were fabricated as fenofibrate/PVP/sodium lauryl sulphate (SLS), fenofibrate/HP-β-CD and fenofibrate/gelatin at the best selected weight ratios of 2.5:4.5:1, 1:4 and 1:8, respectively. The three solid-state preparations were obtained using the solvent-evaporation method through the spray-drying technique. The exploration of physicochemical properties of these nanoparticles was carried out using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Their physicochemical characteristics, aqueous solubility, dissolution rate and pharmacokinetic assessment in rats were explored in comparison with the drug powder. Among the trialled hydrophilic components, PVP, HP-β-CD, gelatin and SLS furnished better solubility and were chosen as the most apt carriers for different nanoparticulated formulations. All of the nanoparticle preparations remarkably enhanced the aqueous solubility, dissolution rate and oral bioavailability of fenofibrate compared to the drug powder. The drug existed in the amorphous state in HP-β-CD nanocorpuscles; on the other hand, in other nanoparticle preparations, it appeared in the crystalline form with a diminished intensity. The aqueous solubility and dissolution rates of the nanoparticles (after 30 min) were not significantly different from one another. Amongst the nanoparticulated formulations trialled in the present research, the initial dissolution rates (up to 10 min) were higher with the PVP nanospheres and HP-β-CD nanocorpuscles; nevertheless, neither of them exhibited the highest oral bioavailability. In spite of comparatively inferior dissolution rate, gelatin nanocapsules demonstrated the highest seeming aqueous solubility and showed the most ameliorated oral bioavailability of the drug (~5.5 fold), due to improved wetting and reduction in crystalline intensity. Fenofibrate-loaded gelatin nanocapsules achieved using the solvent-evaporation method through the spray-drying technique might be a promising system for oral delivery of poorly water-soluble fenofibrate with a bettered bioavailability.
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GRADUATE SCHOOL[S](대학원) > PHARMACY(약학과) > Theses (Ph.D.)
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