title: Controlled release of ziprasidone solid dispersion systems from osmotic pump tablets with enhanced bioavailability in the fasted state.
abstract: OBJECTIVE
  The purpose of this work was to develop a controlled release of ziprasidone with no food effect by the osmotic release strategy.
  
  
  METHODS
  The solution of ziprasidone and poloxamer188 (P188) with different weight ratios was spray-dried to form solid dispersion of ziprasidone (SD-ZIP). The SD-ZIP was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (X-RD) and solubility testing. The SD-ZIP osmotic pump tablets were prepared by wet granulation method. The effect of formulation variables on the release characteristic was investigated. The SD-ZIP osmotic pump tablets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation Zeldox® as a control.
  
  
  RESULTS
  The results of DSC and X-RD indicated that ziprasidone resides in P188 with no crystalline changes. Solubility studies demonstrated that the solubility of SD-ZIP was substantially improved compared to ziprasidone and physical mixtures of ziprasidone and P188. The optimized formulation and drug release profiles of SD-ZIP osmotic pump tablets in different medium were obtained which showed typical osmotically controlled release and could fitted to zero-order kinetics with good linear correlation. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions and no food effect was achieved simultaneously in SD-ZIP osmotic pump tablet compared with Zeldox®.
  
  
  CONCLUSIONS
  The SD-ZIP osmotic pump tablet could be able to enhance the bioavailability in the fasted state and showed sustained release with prolonged actions.
authors.affiliation: School of Biotechnology and Pharmaceutical Engineering and.
authors.forename: Miao
authors.initials: M
authors.lastname: Yanfei
authors.forename: Chen
authors.initials: C
authors.lastname: Guoguang
authors.forename: Ren
authors.initials: R
authors.lastname: Lili
authors.forename: Ouyang
authors.initials: O
authors.lastname: Pingkai
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D005215:Fasting / Q000378:metabolism*; D009997:Osmotic Pressure; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013607:Tablets; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D010879:Piperazines; D013607:Tablets; D013844:Thiazoles; C092292:ziprasidone
keywords: Bioavailability enhancement; controlled release; osmotic pump tablet; solid dispersion; ziprasidone