title: Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.
abstract: The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.
authors.affiliation: a School of Biotechnology and Pharmaceutical Engineering , Nanjing Tech University , Nanjing , China and.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Miao
authors.affiliation: b School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Chen
authors.affiliation: b School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: a School of Biotechnology and Pharmaceutical Engineering , Nanjing Tech University , Nanjing , China and.
authors.forename: Ouyang
authors.initials: O
authors.lastname: Pingkai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D004655:Emulsions / Q000737:chemistry* / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D005989:Glycerides; D010879:Piperazines; D013501:Surface-Active Agents; D013844:Thiazoles; C440220:Labrasol; D011092:Polyethylene Glycols; C092292:ziprasidone
keywords: Bioavailability enhancement; food effect; self-nanoemulsifying; sustained release; ziprasidone