Inclusion complexes of cannabidiol with β-cyclodextrin and its derivative: Physicochemical properties, water solubility, and antioxidant activity

Abstract Cannabidiol (CBD), which has a wide variety of biological activities, is one of the phytocannabinoids from Cannabis sativa L. However, due to the poor aqueous solubility, its applications in food, cosmetic, and pharmaceutical fields are limited. Moreover, the previous researches on the improvement in the solubility of CBD are rare. Cyclodextrins (CDs) are useful materials to improve the solubility of poorly water-soluble molecules. Therefore, this work was aimed to study the physicochemical properties, water solubility, and dissolution rate of the inclusion complexes of CBD with β-cyclodextrin (β-CD) and 2, 6-di-O-methyl-β-cyclodextrin (DM-β-CD), and to determine the influence of complexation on the antioxidant activity of CBD. Job’s plot and phase solubility study revealed that CBD formed inclusion complexes with β-CD and DM-β-CD at a 1:1 stoichiometric ratio. The thermodynamics analysis demonstrated that the inclusion process was spontaneous and endothermic. Then, the inclusion complexes of CBD with β-CD or DM-β-CD were prepared and characterized by PXRD, FT-IR, DSC, SEM, and 1H NMR. The loading efficiency (LE) of the two inclusion complexes was 20.4% and 17.7% respectively, while the complexation efficiency (CE) was 92.4% and 90.8% respectively. Moreover, the results of molecular docking further showed that CBD was encapsulated successfully. The results also displayed that the water solubility of CBD in CBD/β-CD inclusion complex (IC) and CBD/DM-β-CD IC was significantly increased to 0.395 and 14.118 μg/mL, which was enhanced by 17-fold and 614-fold respectively at such a high LE, and the in vitro dissolution rate of CBD was also promoted after complexation. Besides, the antioxidant activity of CBD was improved after encapsulation with β-CD and DM-β-CD. Significantly, the ABTS free radical scavenging ability of the two inclusion complexes was better than that of Vitamin C (Vc).