Microencapsulation and molecular simulation of menthol with various β-cyclodextrins: effects of embedding structures on stability

Menthol was microencapsulated with various β-cyclodextrins (β-CDs), including β-cyclodextrin (β-CD), methyl-β-cyclodextrin (ME-β-CD), and β-cyclodextrin polymer (β-CDEP), via spray-drying to enhance its water solubility and stability. This study aimed to elucidate the embedding mechanisms of menthol with the three β-CDs and identify the optimal derivative for menthol encapsulation. Thermodynamic parameters indicated that the formation of inclusion microcapsules was an exothermic and spontaneous process. Combining experiments and molecular docking revealed that menthol was embedded in the cavities of the three β-CDs by distinct mechanisms. Specifically, no hydrogen bonding was observed between menthol and β-CD, with a binding energy of −2.759 kcal/mol. In contrast, menthol formed hydrogen bonds with ME-β-CD and β-CDEP, with binding energies of −3.249 kcal/mol and −5.019 kcal/mol, respectively. Thermogravimetric (TG), differential scanning calorimetry (DSC), and the release and retention rates at different temperatures demonstrated that all three β-CDs significantly enhanced the thermal stability of menthol. Among them, menthol/β-CDEP microcapsules exhibited the highest thermal stability and sustained-release performance during storage and heating. Additionally, the influence of different embedding structures on the stability of menthol-loaded inclusion microcapsules was investigated. • Menthol/β-CDEP exhibited highest stability (−5.019 kcal/mol) and sustained release. • Hydrogen bonds between menthol and ME-β-CD/β-CDEP enhance stability vs. β-CD (−2.759 kcal/mol). • β-CDEP's flexible cavity achieved highest embedding rate (90.7 %) for menthol.