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The purpose of this study was to investigate the interactions between vinpocetine (VP), sulfobutyl ether beta-cyclodextrin (SBEbetaCD) and the water-soluble polymers polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC). The water-soluble polymers were shown to improve the complexation efficiency of SBEbetaCD, and thus less SBEbetaCD was needed to prepare solid VP-SBEbetaCD complexes in the presence of the polymers. The interactions between VP and SBEbetaCD, with or without PVP or HPMC, were thoroughly investigated in aqueous solutions using the phase-solubility method as well as in the solid state. The amount of VP solubilized in water or aqueous polymer solution increased linearly with increasing SBEbetaCD concentration, demonstrating A(L)-type plots. We estimated the apparent stability constant (K(c)) at room temperature of VP-SBEbetaCD binary complex to be 340 M(-1) and this value increased to 490 M(-1) or 390 M(-1), respectively, with the addition of PVP and HPMC, assuming a 1 : 1 VP-SBEbetaCD molar ratio. Improvement in the K(c) values for ternary complexes clearly confirmed the benefit of the addition of water-soluble polymers to promote higher complexation efficiency. Solid VP-SBEbetaCD binary and ternary systems were prepared by physical mixing, kneading, coevaporation, and lyophilization methods and fully characterized by scanning electron microscopy, differential scanning calorimetry, and X-ray diffractometry. The results obtained suggest that coevaporation and lyophilization methods yield a higher degree of amorphous entities and indicated formation of VP-SBEbetaCD binary and ternary complexes.

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This work deals with multicomponent complex formation of vinpocetine (VP) with beta-cyclodextrin (betaCD), sulfobutyl ether beta-cyclodextrin (SBEbetaCD) 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 ((1)H NMR) studies. TA demonstrated a synergistic effect on VP solubility, and in the complexation efficiency of betaCD and SBEbetaCD. 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. SBEbetaCD was more effective in VP solubilization, as K(C) values of VP-SBEbetaCD-TA multicomponent complexes were notably higher than in corresponding betaCD 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 betaCD and SBEbetaCD. 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 SBEbetaCD multicomponent complexes, since additional interactions with the sulfobutyl side chains were evidenced.

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