title: Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug.
abstract: BACKGROUND
  Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate.
  
  
  METHODS
  LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat.
  
  
  RESULTS
  The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC0- t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug.
  
  
  CONCLUSIONS
  Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA.
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Kazi
authors.initials: K
authors.lastname: Mohsin
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Rayan
authors.initials: R
authors.lastname: Alamri
authors.affiliation: Department of Clinical Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ajaz
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Fars K
authors.initials: FK
authors.lastname: Alanazi
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Health Science University, Clovis, CA, USA.
authors.forename: Muhammad Delwar
authors.initials: MD
authors.lastname: Hussain
mesh_terms: D065966:Absorption, Physicochemical; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics; D011345:Fenofibrate / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066292:Lipid Droplets / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000494:pharmacology; D014867:Water / Q000737:chemistry*
chemical_list: D004655:Emulsions; D013501:Surface-Active Agents; D014867:Water; D011345:Fenofibrate
keywords: fenofibrate; lipid-based formulation; oral bioavailability; self-nanoemulsifying drug delivery systems; solubility improvement