Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect.

Objectives 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. Key findings 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. [ABSTRACT FROM AUTHOR]