caa a22 4500 445313587 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0415-8 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0415-8 Enhanced Oral Bioavailability of Vinpocetine Through Mechanochemical Salt Formation: Physico-Chemical Characterization and In Vivo Studies [Elektronische Daten] [Dritan Hasa, Dario Voinovich, Beatrice Perissutti, Mario Grassi, Alois Bonifacio, Valter Sergo, Cinzia Cepek, Michele Chierotti, Roberto Gobetto, Stefano Dall'Acqua, Sergio Invernizzi] 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. Springer Science+Business Media, LLC, 2011 mechanochemical reaction/activation nationallicence oral absorption nationallicence physico-chemical characterization nationallicence solvent-free process nationallicence vinpocetine citrate nationallicence Hasa Dritan Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut Voinovich Dario Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut Perissutti Beatrice Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut Grassi Mario Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut Bonifacio Alois Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut Sergo Valter Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut Cepek Cinzia CNR-IOM, TASC National Laboratory, Area Science Park, S.S. 14, km 163.5 Basovizza, 34149, Trieste, Italy aut Chierotti Michele Department of Chemistry I.F.M., Laboratory of NMR Spectroscopy, University of Torino, Via P. Giuria 7, 10125, Turin, Italy aut Gobetto Roberto Department of Chemistry I.F.M., Laboratory of NMR Spectroscopy, University of Torino, Via P. Giuria 7, 10125, Turin, Italy aut Dall'Acqua Stefano Department of Pharmaceutical Sciences, University of Padova, via F. Marzolo 5, 35131, Padova, Italy aut Invernizzi Sergio Department of Life Sciences, University of Trieste, Via Giorgieri 10, 34127, Trieste, Italy aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1870-1883 0724-8741 28:8<1870 2011 28 11095 https://doi.org/10.1007/s11095-011-0415-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0415-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hasa Dritan Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Voinovich Dario Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Perissutti Beatrice Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Grassi Mario Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Bonifacio Alois Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Sergo Valter Department of Industrial Engineering and Information Technology, University of Trieste, via Valerio 10, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Cepek Cinzia CNR-IOM, TASC National Laboratory, Area Science Park, S.S. 14, km 163.5 Basovizza, 34149, Trieste, Italy aut NATIONALLICENCE 700 1- Chierotti Michele Department of Chemistry I.F.M., Laboratory of NMR Spectroscopy, University of Torino, Via P. Giuria 7, 10125, Turin, Italy aut NATIONALLICENCE 700 1- Gobetto Roberto Department of Chemistry I.F.M., Laboratory of NMR Spectroscopy, University of Torino, Via P. Giuria 7, 10125, Turin, Italy aut NATIONALLICENCE 700 1- Dall'Acqua Stefano Department of Pharmaceutical Sciences, University of Padova, via F. Marzolo 5, 35131, Padova, Italy aut NATIONALLICENCE 700 1- Invernizzi Sergio Department of Life Sciences, University of Trieste, Via Giorgieri 10, 34127, Trieste, Italy aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1870-1883 0724-8741 28:8<1870 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer