Sulfobutyl‐β‐Cyclodextrin‐Based Inclusion Complexes of Menthol, Menthone, and Menthylamide: Preparation, Characterization, and Sustained‐Release Properties

ABSTRACT Three inclusion complexes of menthol, menthone, and menthyl amide with sulfobutyl‐β‐cyclodextrin (SBE‐β‐CD) were prepared using the co‐precipitation method followed by freeze‐drying, with SBE‐β‐CD serving as the wall material and the cooling agents as the core materials. Their structure, morphology, and composition are characterized by powder x‐ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy, while nuclear magnetic resonance and thermogravimetric analysis provide further insights. The inclusion complexes show high entrapment efficiency, with menthol/SBE‐β‐CD reaching 87.82%, much higher than menthone/SBE‐β‐CD (26.27%) and menthyl amide/SBE‐β‐CD (23.62%). All complexes exhibit pyrolysis temperatures above 270°C, confirming enhanced thermal stability compared to the free cooling agents. At 25°C–120°C, the cumulative release of menthone/SBE‐β‐CD remains between 4.49% and 39.94%, demonstrating good sustained‐release performance. The release behavior follows the Weibull model, indicating a relatively complex mechanism.