title: Investigation and physicochemical characterization of vinpocetine-sulfobutyl ether beta-cyclodextrin binary and ternary complexes.
abstract: 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.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-004 Coimbra, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Ribeiro
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
mesh_terms: D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D014748:Vinca Alkaloids / Q000032:analysis / Q000737:chemistry*; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D014748:Vinca Alkaloids; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; C013983:vinpocetine