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Pharmaceutical Research

, Volume 28, Issue 8, pp 1870–1883 | Cite as

Enhanced Oral Bioavailability of Vinpocetine Through Mechanochemical Salt Formation: Physico-Chemical Characterization and In Vivo Studies

  • Dritan Hasa
  • Dario Voinovich
  • Beatrice Perissutti
  • Mario Grassi
  • Alois Bonifacio
  • Valter Sergo
  • Cinzia Cepek
  • Michele R. Chierotti
  • Roberto Gobetto
  • Stefano Dall’Acqua
  • Sergio Invernizzi
Research Article

ABSTRACT

Purpose

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.

Conclusion

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.

KEY WORDS

mechanochemical reaction/activation oral absorption physico-chemical characterization solvent-free process vinpocetine citrate 

Notes

ACKNOWLEDGMENTS

The authors thank Linnea (Locarno, CH) and Covex (Madrid, ES) for kindly donating the active ingredients used in this study, D. Lenaz for his precious advices and S. Bhardwaj, from TASC-IOM-CNR AREA Science Park, Trieste, Italy, for assistance during XPS analyses.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Dritan Hasa
    • 1
  • Dario Voinovich
    • 1
  • Beatrice Perissutti
    • 1
  • Mario Grassi
    • 2
  • Alois Bonifacio
    • 2
  • Valter Sergo
    • 2
  • Cinzia Cepek
    • 3
  • Michele R. Chierotti
    • 4
  • Roberto Gobetto
    • 4
  • Stefano Dall’Acqua
    • 5
  • Sergio Invernizzi
    • 6
  1. 1.Department of Chemical and Pharmaceutical SciencesUniversity of TriesteTriesteItaly
  2. 2.Department of Industrial Engineering and Information TechnologyUniversity of TriesteTriesteItaly
  3. 3.CNR-IOM, TASC National LaboratoryTriesteItaly
  4. 4.Department of Chemistry I.F.M., Laboratory of NMR SpectroscopyUniversity of TorinoTurinItaly
  5. 5.Department of Pharmaceutical SciencesUniversity of PadovaPadovaItaly
  6. 6.Department of Life SciencesUniversity of TriesteTriesteItaly

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