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

Abstract

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 100A˚ ; 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.

Description

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.

Keywords

Citation

Hasa, D. et al. (2012) Mechanochemically induced disordered structures of vincamine: The different mediation of two cross-linked polymers. International Journal of Pharmaceutics, 436 (1-2), pp. 41-57

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)