title: Optimized zein nanospheres for improved oral bioavailability of atorvastatin.
abstract: BACKGROUND
  This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug.
  
  
  METHODS
  Twelve experimental runs of atorvastatin-zein nanosphere formula were formulated by a liquid-liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin-zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet.
  
  
  RESULTS
  The optimized atorvastatin-zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin-zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet.
  
  
  CONCLUSIONS
  The atorvastatin-zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Fahima M
authors.initials: FM
authors.lastname: Hashem
authors.affiliation: Holding Company for Biological Products and Vaccines, Giza, Egypt.
authors.forename: Majid M
authors.initials: MM
authors.lastname: Al-Sawahli
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nasr
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Osama A A
authors.initials: OA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D054118:Nanospheres / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D015028:Zein / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D015028:Zein; D000069059:Atorvastatin
keywords: experimental design; fractional factorial design; nanoparticles; optimization