Characterization and Evaluation of Ternary Complexes of Ascorbic Acid with γ-Cyclodextrin and Poly(vinyl Alcohol)

Ascorbic acid (AA) is a general antioxidant used in aqueous pharmaceutical formulations. However, in aqueous solutions, AA is unstable and easily oxidized when exposed to air, light and/or heat. Cyclodextrins are well known for their ability to form inclusion complexes with various compounds to improve their solubility and stability. Previous studies demonstrate that cyclodextrins preserve the antioxidant capacity of AA but data for gamma-cyclodextrin (gamma CD) have not been reported. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer widely used as a drug matrix in various pharmaceutical fields, but its application for drug stabilization is limited. This study aimed to investigate the protective ability of gamma CD on AA through the formation of ternary complexes with PVA. Binary (i.e., AA/gamma CD, AA/PVA and gamma CD/PVA) and ternary (i.e., AA/gamma CD/PVA) complexes were first confirmed. It was reported that those complexes were formed through interactions between the heterocyclic ring of AA, hydroxyl group of PVA and hydrophobic cavity of gamma CD. The hydrodynamic diameter of complexes was then studied. It was found that the diameter of gamma CD/PVA complexes increased with respect to the concentration of gamma CD. Higher gamma CD concentrations also resulted in increasing hydrodynamic diameters of the ternary complex. The presence of AA in ternary complexes interfered with the aggregation tendency of gamma CD/PVA binary complexes. Furthermore, the antioxidant capacity of AA in binary and ternary complexes was investigated. It was found that the presence of gamma CD preserved the antioxidant activity of AA, whereas PVA showed a contrasting effect. The influence of gamma CD and PVA concentration on antioxidant capacity was then studied through central composite design (CCD). Even though the concentration of gamma CD significantly affected the inhibition efficiency of the ternary complex, the insignificant influence of PVA could not be ignored. A promising protective ternary complex should consist of an optimized concentration of PVA and a high concentration of gamma CD.