Ribeiro Laura, Loftsson Thorsteinn, Ferreira Domingos, Veiga Francisco
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-004 Coimbra, Portugal.
Chem Pharm Bull (Tokyo). 2003 Aug;51(8):914-22. doi: 10.1248/cpb.51.914.
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.
本研究的目的是探究长春西汀（VP）、磺丁基醚β-环糊精（SBEβCD）与水溶性聚合物聚乙烯吡咯烷酮（PVP）和羟丙基甲基纤维素（HPMC）之间的相互作用。结果表明，水溶性聚合物可提高SBEβCD的包合效率，因此在聚合物存在的情况下，制备固体VP-SBEβCD复合物所需的SBEβCD较少。采用相溶解度法以及在固态下，对VP与SBEβCD之间在有无PVP或HPMC情况下的相互作用进行了深入研究。溶解在水或聚合物水溶液中的VP量随SBEβCD浓度的增加呈线性增加，呈现A(L)型曲线。我们估计VP-SBEβCD二元复合物在室温下的表观稳定常数（K(c)）为340 M(-1)，假设VP与SBEβCD的摩尔比为1:1，加入PVP和HPMC后，该值分别增加到490 M(-1)或390 M(-1)。三元复合物K(c)值的提高清楚地证实了添加水溶性聚合物以促进更高包合效率的益处。通过物理混合、捏合、共蒸发和冻干法制备了固体VP-SBEβCD二元和三元体系，并通过扫描电子显微镜、差示扫描量热法和X射线衍射法进行了全面表征。所得结果表明，共蒸发和冻干法产生的无定形实体程度更高，并表明形成了VP-SBEβCD二元和三元复合物。
