Mechanochemically induced disordered structures of vincamine: the different mediation of two cross-linked polymers.
The aims of this research were to prepare highly bioavailable binary cogrounds (vincamine-AcDiSol(®) or PVP-Cl) by means of a mechanochemical process and to study the mediation of each polymer in the induction of physical transformations of the drug. From a set of fifteen cogrounds for each crosslinked polymer, two samples were selected in each group on the basis of the AUC of in vitro dissolution profiles with the help of a statistical comparison. The chosen samples were analysed by means of TEM, XRPD, Raman-spectroscopy/imaging, SSNMR, also including the study of (1)H spin-lattice relaxation times. The research encompassed in vivo oral absorption studies in rats, pharmacokinetic analysis and physical stability studies during 1 year. An intimate drug-polymer mixing was found in the coground samples with domain average dimensions smaller than 100 Å; this reflected in a remarkable enhancement of the in vitro and in vivo bioavailability. Different disordered states were detected in the coground samples as a function of cogrinding time and the type and amount of polymer used. Though both crosslinked polymers produced a remarkable enhancement of the oral bioavailability, coground systems based on AcDiSol(®) are preferable in terms of pharmacokinetic performance and physical stability.
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, I-34127 Trieste, Italy.
Dritan
D
Hasa
Beatrice
B
Perissutti
Michele Remo
MR
Chierotti
Roberto
R
Gobetto
Iztok
I
Grabnar
Alois
A
Bonifacio
Stefano
S
Dall'Acqua
Sergio
S
Invernizzi
Dario
D
Voinovich
D000818:Animals; D001682:Biological Availability; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011205:Povidone / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014749:Vincamine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
D004337:Drug Carriers; D011108:Polymers; D014665:Vasodilator Agents; D014749:Vincamine; D011205:Povidone; D002266:Carboxymethylcellulose Sodium