title: Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect.
abstract: OBJECTIVE
  The purpose of this work was to develop ziprasidone-phospholipid complex (ZIP-PLC) in sustained-release pellets to enhance the oral bioavailability and overcome the food effect of ziprasidone.
  
  
  METHODS
  Ziprasidone-phospholipid complex was formulated by solvent-evaporation method. The complexes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and solubility testing. The optimized ZIP-PLC was used to prepare ZIP-PLC sustained-release pellets via extrusion-spheronization method. The pellets were characterized by in vitro drug-release studies and administered to fasted and fed beagle dogs, and their pharmacokinetics were compared with commercial formulation Zeldox capsule as a control.
  
  
  RESULTS
  The results of FTIR, SEM, DSC and PXRD studies confirmed the formation of phospholipid complex. Solubility studies showed there was a higher solubility in water for ZIP-PLC than monohydrate ziprasidoe. The in vitro release rate of ziprasidone from the ZIP-PLC sustained-release pellet exhibited controlled-release characteristics with over 95% total release in 12 h. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions, and no food effect was achieved simultaneously in ZIP-PLC sustained-release pellet compared with Zeldox capsule.
  
  
  CONCLUSIONS
  The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.
authors.affiliation: School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Miao
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China.
authors.forename: Pingkai
authors.initials: P
authors.lastname: Ouyang
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004285:Dogs; D018565:Food-Drug Interactions; D008855:Microscopy, Electron, Scanning; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000277:Adjuvants, Pharmaceutic; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D010743:Phospholipids; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone
keywords: bioavailability enhancement; food effect; phospholipid complex; sustained release; ziprasidone