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

被引:13
作者
Hasa, Dritan [1 ]
Perissutti, Beatrice [1 ]
Chierotti, Michele Remo [2 ]
Gobetto, Roberto [2 ]
Grabnar, Iztok [3 ]
Bonifacio, Alois [4 ]
Dall'Acqua, Stefano [5 ]
Invernizzi, Sergio [6 ]
Voinovich, Dario [1 ]
机构
[1] Univ Trieste, Dept Chem & Pharmaceut Sci, I-34127 Trieste, Italy
[2] Univ Turin, Dept Chem IFM, Lab NMR Spect, I-10125 Turin, Italy
[3] Univ Ljubljana, Chair Biopharmaceut & Pharmacokinet, Ljubljana, Slovenia
[4] Univ Trieste, Dept Ind & Informat Engn, I-34127 Trieste, Italy
[5] Univ Padua, Dept Pharmaceut Sci, I-35131 Padua, Italy
[6] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy
关键词
Vincamine; Mechanochemical activation; Cross-linked polymers; Physico-chemical characterisation; Bioavailability; Physical stability; ORAL BIOAVAILABILITY; DISSOLUTION; VINPOCETINE; ENHANCEMENT;
D O I
10.1016/j.ijpharm.2012.06.024
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aims of this research were to prepare highly bioavailable binary cogrounds (vincamine-AcDiSol (R) 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 H-1 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 A; 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 (R) are preferable in terms of pharmacokinetic performance and physical stability. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:41 / 57
页数:17
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