Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies

This work deals with multicomponent complex formation of vinpocetine (VP) with β-cyclodextrin (βCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and tartaric acid (TA), in the presence or absence of water-soluble polymers, in aqueous solution. Complexation was monitored by phase-solubility and proton n...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2005, Vol.24 (1), p.1-13
Main Authors: Ribeiro, Laura, Carvalho, Rui A., Ferreira, Domingos C., Veiga, Francisco J.B.
Format: Article
Language:English
Subjects:
1H NMR
Biological and medical sciences
Chemistry, Pharmaceutical
Cyclodextrins
Cyclodextrins - analysis
Cyclodextrins - chemistry
General pharmacology
Medical sciences
Multicomponent complexes
Nuclear Magnetic Resonance, Biomolecular - methods
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phase-solubility studies
Polymers - analysis
Polymers - chemistry
Solubility - drug effects
Tartrates - analysis
Tartrates - chemistry
Vinca Alkaloids - analysis
Vinca Alkaloids - chemistry
Vinpocetine
Water - analysis
Water - chemistry
Water-soluble polymers
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Summary:This work deals with multicomponent complex formation of vinpocetine (VP) with β-cyclodextrin (βCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and tartaric acid (TA), in the presence or absence of water-soluble polymers, in aqueous solution. Complexation was monitored by phase-solubility and proton nuclear magnetic resonance ( 1H NMR) studies. TA demonstrated a synergistic effect on VP solubility, and in the complexation efficiency of βCD and SBEβCD. Additionally, water-soluble polymers increased even more the complexation efficiency of the CDs that was reflected by a 2.1–2.5 increase on K C values for VP–CD–TA–polymer multicomponent complexes. SBEβCD was more effective in VP solubilization, as K C values of VP–SBEβCD–TA multicomponent complexes were notably higher than in corresponding βCD complexes. The large chemical shift displacements from protons located in the interior of the hydrophobic CD cavities (i.e., H-3 and H-5) coupled with significant chemical shift displacements of VP aromatic protons suggested that this moiety was included in the cavity of both βCD and SBEβCD. Two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments were carried out in order to obtain information about the multicomponent complex geometry in solution. Inspection of ROESY spectra allowed the establishment of spatial proximities between all aromatic protons of VP and the internal protons of the CDs, confirming that the aromatic moiety of VP is included in CD cavities being deeply inserted in SBEβCD multicomponent complexes, since additional interactions with the sulfobutyl side chains were evidenced.
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2004.09.003