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 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.
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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
Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)
Peer Reviewed : Yes
- Leicester School of Pharmacy