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.
