Compared to beta-cyclodextrins (beta-CD), hydroxypropyl-beta-cyclodextrins (HP-beta-CD) are a more popular material used to prepare inclusion complexes due to their superior solubility and intestinal absorption. In this study, oleuropein (OL) inclusion complexes with beta-CD (beta-CD:OL) and HP-beta-CD (HP-beta-CD:OL) were prepared and the formation of inclusion complexes was validated by IR, PXRD, and DSC. A phase solubility test showed that the lgK (25 °C) and binding energy of beta-CD:OL and HP-beta-CD:OL was 2.32 versus 1.98, and −6.1 versus −24.66 KJ/mol, respectively. Beta-CD:OL exhibited a more powerful effect than HP-beta-CD:OL in protecting OL from degradation upon exposure to light, high temperature and high humidity. Molecular docking, peak intensity of carbonyls in IR, and ferric reducing power revealed that beta-CD:OL formed more hydrogen bonds with the unstable groups of OL. Both inclusion complexes significantly enhanced the solubility, intestinal permeation and antioxidant activity of OL (p < 0.05). Though HP-beta-CD:OL had higher solubility and intestinal absorption over beta-CD:OL, the difference was not significant (p > 0.05). The study implies that lower binding energy is not always associated with the higher stability of a complex. Beta-CD can protect a multiple-hydroxyl compound more efficiently than HP-beta-CD with the intestinal permeation comparable to HP-beta-CD complex.

Background: Cyclodextrins (CDs) are commonly used host molecules of inclusion complex. However, due to the lack of sensitive method to determine CDs, the absorption process of CDs remains unclear. Objective: In this study, oleuropein (OL) inclusion complex employing hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) as host molecules was prepared and the formation of inclusion complex was ascertained by FT-IR and DSC. A spectrophotometry was established for the determination of HP-beta-CD, based on the fact that the absorbance of phenolphthalein (PP) decreased in the presence of HP-beta-CD. Methods: The assay conditions were optimized to augment the method sensitivity. Molecular docking was employed to verify the strong interaction between PP and HP-beta-CD. The permeation process of free HP-beta-CD, HP-beta-CD of OL inclusion complex, free OL, and OL in the inclusion complex, was examined, respectively, using an in vitro mouse small intestine model. Results: Though HP-beta-CD possessed hydrophilic outside shell, it could permeate through mouse small intestine quickly with cumulative permeating amount over 90% in 2 h. Free HP-beta-CD, the host molecule HP-beta-CD, and guest molecule OL of the inclusion complex exhibited the consistent permeating profiles across mouse small intestine. Conclusion: The approach for the determination of HP-beta-CD was accurate and precise (%RSD=2.98).