title: Enhanced oral bioavailability of lurasidone by self-nanoemulsifying drug delivery system in fasted state.
abstract: OBJECTIVE
  The purpose of this work was to develop a new formulation to enhance the bioavailability and reduce the food effect of lurasidone using self-nanoemulsifying drug delivery systems (SNEDDSs).
  
  
  METHODS
  The formulation of lurasidone-SNEDDS was selected by the solubility and pseudo-ternary phase diagram studies. The prepared lurasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis, zeta potential and in vitro drug release. Lurasidone-SNEDDSs were administered to beagle dogs in fed and fasted state and their pharmacokinetics were compared to commercial available tablet as a control.
  
  
  RESULTS
  The result showed lurasidone-SNEDDS was successfully prepared using Capmul MCM, Tween 80 and glycerol as oil phase, surfactant and co-surfactant, respectively. In vitro drug release studies indicated that the lurasidone-SNEDDS showed improved drug release profiles and the release behavior was not affected by the medium pH with total drug release of over 90% within 5 min. Pharmacokinetic study showed that the AUC(0-∞) and Cmax for lurasidone-SNEDDS are similar in the fasted and fed state, indicating essentially there is no food effect on the drug absorption.
  
  
  CONCLUSIONS
  It was concluded that enhanced bioavailability and no food effect of lurasidone had been achieved by using SNEDDS.
authors.affiliation: a School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University , Nanjing , China ;
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Miao
authors.affiliation: b College of Marxism, Nanjing Tech University , Nanjing , China ;
authors.forename: Jiqin
authors.initials: J
authors.lastname: Sun
authors.affiliation: c School of Pharmaceutical Sciences, Nanjing Tech University , Nanjing , China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Chen
authors.affiliation: c School of Pharmaceutical Sciences, Nanjing Tech University , Nanjing , China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lili
authors.affiliation: a School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University , Nanjing , China ;
authors.forename: Pingkai
authors.initials: P
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics*; D005990:Glycerol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D000069056:Lurasidone Hydrochloride / Q000737:chemistry* / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004655:Emulsions; D011136:Polysorbates; D013501:Surface-Active Agents; D013607:Tablets; D000069056:Lurasidone Hydrochloride; D005990:Glycerol
keywords: Bioavailability enhancement; food effect; lurasidone; self-nanoemulsifying; solubility