title: Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate.
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea; Faculty of Pharmacy, University of Central Punjab, Johar, Lahore, Pakistan.
authors.forename: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Omer
authors.initials: O
authors.lastname: Mustapha
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Dong Shik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Kyeong Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Sung Giu
authors.initials: SG
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan, North Gyeongsang, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, South Korea.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan, North Gyeongsang, South Korea.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D011345:Fenofibrate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000960:Hypolipidemic Agents; D011208:Powders; D014867:Water; D011205:Povidone; D011345:Fenofibrate
keywords: electrospray technique; enhanced bioavailability; fenofibrate; nanospherule
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