Exploring the formation mechanism of ferulic acid/hydroxypropyl‐β‐cyclodextrin inclusion complex: spectral analyses and computer simulation

Abstract BACKGROUND The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl‐ β ‐cyclodextrin (HP‐ β ‐CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP‐ β ‐CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP‐ β ‐CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. RESULTS The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP‐ β ‐CD. Thermogravimetry‐derivative thermogravimetry (TG‐DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP‐ β ‐CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP‐ β ‐CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP‐ β ‐CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP‐ β ‐CD. CONCLUSIONS The findings of this study have contributed to a deeper understanding of the interactions between FA and HP‐ β ‐CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.