title: Silica encapsulated lipid-based drug delivery systems for reducing the fed/fasted variations of ziprasidone in vitro.
abstract: Ziprasidone is a poorly water-soluble antipsychotic drug that demonstrates low fasted state oral bioavailability and a clinically significant two-fold increase in absorption when dosed postprandially. Owing to significant compliance challenges faced by schizophrenic patients, a novel oral formulation of ziprasidone that demonstrates improved fasted state absorption and a reduced food effect is of major interest, and is therefore the aim of this research. Three lipid-based drug delivery systems (LBDDS) were developed and investigated: (a) a self-nanoemulsifying drug delivery system (SNEDDS), (b) a solid SNEDDS formulation, and (c) silica-lipid hybrid (SLH) microparticles. SNEDDS was developed using Capmul MCM® and Tween 80®, and solid SNEDDS was fabricated by spray-drying SNEDDS with Aerosil 380® silica nanoparticles as the solid carrier. SLH microparticles were prepared in a similar manner to solid SNEDDS using a precursor lipid emulsion composed of Capmul MCM® and soybean lecithin. The performance of the developed formulations was evaluated under simulated digesting conditions using an in vitro lipolysis model, and pure (unformulated) ziprasidone was used as a control. While pure ziprasidone exhibited the lowest rate and extent of drug solubilization under fasting conditions and a significant 2.4-fold increase in drug solubilization under fed conditions, all three LBDDS significantly enhanced the extent of drug solubilization under fasting conditions between 18- and 43-folds in comparison to pure drug. No significant difference in drug solubilization for the fed and fasted states was observed for the three LBDDS systems. To highlight the potential of LBDDS, mechanism(s) of action and various performance characteristics are discussed. Importantly, LBDDS are identified as an appropriate formulation strategy to explore further for the improved oral delivery of ziprasidone.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Tahnee J
authors.initials: TJ
authors.lastname: Dening
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Shasha
authors.initials: S
authors.lastname: Rao
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Nicky
authors.initials: N
authors.lastname: Thomas
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. Electronic address: Clive.Prestidge@unisa.edu.au.
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005215:Fasting; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011136:Polysorbates / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D010879:Piperazines; D011136:Polysorbates; D013844:Thiazoles; D014867:Water; C092292:ziprasidone; D012822:Silicon Dioxide
keywords: Antipsychotic; Food effect; Lipid-based drug delivery systems; Poorly water-soluble drugs; Self-nanoemulsifying drug delivery systems; Silica nanoparticles; Silica–lipid hybrid microparticles; Solid-dosage forms; Solubilization; Ziprasidone