Solid-state structure and physicochemical characterization of the hydrocortisone–β-cyclodextrin inclusion complex

Abstract

The inclusion complex formed between hydrocortisone and β-cyclodextrin was successfully obtained and structurally characterized in the solid state. Single-crystal X-ray diffraction provided direct evidence of hydrocortisone encapsulation within the β-cyclodextrin cavity, revealing a 2:1 host–guest stoichiometry and positional disorder of the guest molecules accommodated within head-to-head β-cyclodextrin dimers.

The crystal packing adopts a channel-type arrangement stabilized by intermolecular hydrogen bonding and hydration networks. Complementary solid-state techniques, including PXRD, DSC–TGA, FT-IR spectroscopy, cryo-SEM, and ¹³C CP/MAS NMR, confirmed the formation of a distinct solid phase with reduced crystallinity and altered physicochemical properties compared with the parent compounds and their physical mixture.

Periodic density functional theory calculations supported the experimental structure, demonstrating that the two crystallographically observed guest orientations represent energetically accessible configurations. Together, these results provide a comprehensive structural description of the hydrocortisone–β-cyclodextrin inclusion complex and clarify the molecular basis of its solid-state organization.

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Materials

Hydrocortisone (97 % pure), was obtained as a white to off-white crystalline powder from BIOSYNTH (Biosynth AG, Staad, Switzerland). Pharmaceutical-grade β-cyclodextrin (β-CD), in the form of a white powder, was purchased from Cyclolab Ltd. (Budapest, Hungary). Both compounds were used as received, without any further purification. Double-distilled water was utilized for the preparation of the examined solution.

Aleksandra Kowalska, Łukasz Szeleszczuk, Kostas Bethanis, Elias Christoforides, Marta K. Dudek, Monika Zielińska-Pisklak, Dariusz Maciej Pisklak, Solid-state structure and physicochemical characterization of the hydrocortisone–β-cyclodextrin inclusion complex, Journal of Molecular Structure, Volume 1360, 2026, 145607, ISSN 0022-2860, https://doi.org/10.1016/j.molstruc.2026.145607.

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