Investigation and Physicochemical Characterization of Vinpocetine-Sulfobutyl Ether b-Cyclodextrin Binary and Ternary Complexes

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Investigation and Physicochemical Characterization of Vinpocetine-Sulfobutyl Ether b-Cyclodextrin Binary and Ternary Complexes
2003
Laura RIBEIRO,a Thorsteinn LOFTSSON,b Domingos FERREIRA,c and Francisco VEIGA*,a
a Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra; 3000?004 Coimbra, Portugal:
b Department of Pharmacy, University of Iceland; P.O. Box 7210, IS-127, Reykjavik, Iceland: and c Laboratory of
Pharmaceutical Technology, Faculty of Pharmacy, University of Porto; 4050?047 Porto, Portugal.
Chem. Pharm. Bull. 51(8) 914?922 (2003) Vol. 51, No. 8
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The purpose of this study was to investigate the interactions between vinpocetine (VP), sulfobutyl ether
beta-cyclodextrin (SBE bCD) and the water-soluble polymers polyvinylpyrrolidone (PVP) and hydroxypropyl
methylcellulose (HPMC). The water-soluble polymers were shown to improve the complexation efficiency of
SBE bCD, and thus less SBE bCD was needed to prepare solid VP?SBE bCD complexes in the presence of the
polymers. The interactions between VP and SBE bCD, 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 SBE bCD concentration, demonstrating
AL-type plots. We estimated the apparent stability constant (Kc) at room temperature of VP?SBE bCD
binary complex to be 340M21 and this value increased to 490M21 or 390 M21, respectively, with the addition of
PVP and HPMC, assuming a 1 : 1 VP?SBE bCD molar ratio. Improvement in the Kc values for ternary complexes
clearly confirmed the benefit of the addition of water-soluble polymers to promote higher complexation ef-
ficiency. Solid VP?SBE bCD 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?SBE bCD binary and ternary
complexes.
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