Mechanochemically induced disordered structures of vincamine: The different mediation of two cross-linked polymers

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• 作者：Dritan Hasa ; Beatrice Perissutti ; Michele Remo Chierotti ; Roberto Gobetto ; Iztok Grabnar ; Alois Bonifacio ; Stefano Dall¡¯Acqua ; Sergio Invernizzi ; Dario Voinovich
• 关键词：Vincamine ; Mechanochemical activation ; Cross-linked polymers ; Physico-chemical characterisation ; Bioavailability ; Physical stability
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 出版时间：15 October, 2012
• 年：2012
• 卷：436
• 期：1-2
• 页码：41-57
• 全文大小：2841 K

文摘

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 ¹H 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 ?; 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.