Pterostilbene (3,5-dimethoxy-4¢-hydroxystilbene, PTB) is a natural dietary polyphenol, occurring primarily in blueberries and Pterocarpus marsupium heartwood. In recent years, this compound has attracted increasing interest owing to its antioxidant, anti-inflammatory and anticarcinogenic properties and its capacity to reduce and regulate cholesterol and sugar blood levels.
It is a methoxylated derivative of resveratrol, a class II compound in the Biopharmaceutics Classification System. The low aqueous solubility of pterostilbene is one factor that limits its utility, and among the different methods available for its improvement is its complexation with cyclodextrins (CDs), the subject of this study.
CDs are natural macrocyclic oligomers composed of a-D-glucose units linked by a-1,4 glycosidic bonds to form torus-shaped molecules. This conformation is responsible for inclusion complex formation with organic molecules, the latter generally being included within the hydrophobic CD cavity. In addition to enhancing the solubility of guest molecules, CD complexation can be used to improve other physicochemical properties such as stability, to prevent gastrointestinal irritation, to reduce or eliminate unpleasant odours and flavours, and to prevent drug-drug or drug-excipient interactions.
In this study, various methods used to prepare inclusion complexes between PTB and three natural cyclodextrins (a-CD, b-CD and g-CD) are described. In addition, the isolation of single crystals of complexes of PTB with b-CD and g-CD was pursued to determine the nature of their host-guest interactions using X-ray diffraction. The structure of a hydrated b-CD·PTB complex crystallizing in the monoclinic space group C2 was successfully resolved, revealing two disordered, diad-related PTB molecules encapsulated within a b-CD dimer. A microcrystalline product obtained by kneading g-CD and PTB was investigated by powder X-ray diffraction, which showed unequivocally that it is an inclusion complex crystallizing in the tetragonal space group P4212. Further characterization of these complexes was performed using thermogravimetry, differential scanning calorimetry and 1H NMR spectroscopy.
