Multidisciplinary approach on characterizing a mechanochemically activated composite of vinpocetine and crospovidone.
Significant improvement of solubilization kinetics of poorly soluble vinpocetine was obtained through a mechanochemical activation process in presence of micronized crospovidone. Drug-to-polymer weight ratio and milling time variables resulted to have statistically significant impacts on the activation of the product. The complete amorphization was obtained in the coground with the highest crospovidone contents (>80% wt), milled for the longest time (180 min). An ad hoc software was then used to calculate the dimensions of the drug crystallites in the samples on the basis of the calorimetric data. The thermal analyses were then accompanied and confirmed by an extensive solid-state characterization, performing X-ray diffraction, Raman imaging/spectroscopy, DRIFT, and SS-NMR spectroscopy, followed by laser diffraction and solubilization kinetics tests. All the analyses agreed on attesting the progressive loosing of crystalline structure of the drug when increasing milling time and amount of polymer in the formulations. This activated status of the drug, which resulted to be homogeneously distributed on the coground sample and stable for at least 1 year, was reflected on favorable solubilization kinetics. The in vivo studies on rats revealed that coground systems promoted a fivefold higher oral bioavailability enhancement in comparison to a commercial formulation (Vimpocetin 5mg Capsules, Pharma).
Hasa
Dritan
D
Department of Pharmaceutical Sciences, University of Trieste, P. le Europa 1, I-34127 Trieste, Italy.
Voinovich
Dario
D
Perissutti
Beatrice
B
Bonifacio
Alois
A
Grassi
Mario
M
Franceschinis
Erica
E
Dall'Acqua
Stefano
S
Speh
Manuela
M
Plavec
Janez
J
Invernizzi
Sergio
S
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D008297:Male; D055595:Mechanical Phenomena; D053758:Nanoparticles; D010316:Particle Size; D010592:Pharmaceutic Aids; D011205:Povidone / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D044366:Transition Temperature; D014748:Vinca Alkaloids / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D010592:Pharmaceutic Aids; D014748:Vinca Alkaloids; C013983:vinpocetine; D011205:Povidone