2003 年 51 巻 8 号 p. 914-922
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 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–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.
