Investigation and physicochemical characterization of vinpocetine- sulfobutyl ether β-cyclodextrin binary and ternary complexes

Abstract

The purpose of this study was to investigate the interactions between vinpocetine (VP), sulfobutyl ether beta-cyclodextrin (SBEβCD) and the water-soluble polymers polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC). The water-soluble polymers were shown to improve the complexation efficiency of SBEβCD, and thus less SBEβCD was needed to prepare solid VP-SBEβCD complexes in the presence of the polymers. The interactions between VP and SBEβCD, 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 SBEβCD concentration, demonstrating AL-type plots. We estimated the apparent stability constant (Kc) at room temperature of VP-SBEβCD binary complex to be 340M-1 and this value increased to 490M-1 or 390 M-1, respectively, with the addition of PVP and HPMC, assuming a 1:1 VP-SBEβCD 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 efficiency. Solid VP-SBEβCD 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-SBEβCD binary and ternary complexes. © 2003 Pharmaceutical Society of Japan.