title: Enhanced oral bioavailability of vinpocetine through mechanochemical salt formation: physico-chemical characterization and in vivo studies.
abstract: OBJECTIVE
  Enhancing oral bioavailability of vinpocetine by forming its amorphous citrate salt through a solvent-free mechanochemical process, in presence of micronised crospovidone and citric acid.
  
  
  METHODS
  The impact of formulation and process variables (amount of polymer and citric acid, and milling time) on vinpocetine solubilization kinetics from the coground was studied through an experimental design. The best performing samples were characterized by employing a multidisciplinary approach, involving Differential scanning calorimetry, X-ray diffraction, Raman imaging/spectroscopy, X-ray photoelectron spectroscopy, solid-state NMR spectroscopy, porosimetry and in vivo studies on rats to ascertain the salt formation, their solid-state characteristics and oral bioavailability in comparison to vinpocetine citrate salt (Oxopocetine(®)).
  
  
  RESULTS
  The analyses attested that the mechanochemical process is a viable way to produce in absence of solvents vinpocetine citrate salt in an amorphous state.
  
  
  CONCLUSIONS
  From the in vivo studies on rats the obtained salt was four times more bioavailable than its physical mixture and bioequivalent to the commercial salt produced by conventional synthetic process implying the use of solvent.
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127 Trieste, Italy.
authors.forename: Dritan
authors.initials: D
authors.lastname: Hasa
authors.forename: Dario
authors.initials: D
authors.lastname: Voinovich
authors.forename: Beatrice
authors.initials: B
authors.lastname: Perissutti
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Alois
authors.initials: A
authors.lastname: Bonifacio
authors.forename: Valter
authors.initials: V
authors.lastname: Sergo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cepek
authors.forename: Michele R
authors.initials: MR
authors.lastname: Chierotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gobetto
authors.forename: Stefano
authors.initials: S
authors.lastname: Dall'Acqua
authors.forename: Sergio
authors.initials: S
authors.lastname: Invernizzi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010316:Particle Size; D056951:Photoelectron Spectroscopy / Q000379:methods; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D014748:Vinca Alkaloids; D019343:Citric Acid; C013983:vinpocetine; D011205:Povidone