Inclusion Complexes of Stearyl Glycyrrhetinate with γ-Cyclodextrin and Cyclodextrin-Based Metal–Organic Frameworks: Solid-State Characterization and Improved Solubility in Fasted-State Simulated Intestinal Fluid

In this study, stearyl glycyrrhetinate (SG), a poorly water-soluble derivative of glycyrrhetinic acid, was formulated into inclusion complexes with γ-cyclodextrin (γCD) and cyclodextrin-based metal-organic frameworks (CD-MOF-1) using the evaporation method (EVP) in the solid state. Powder X-ray diffraction and differential scanning calorimetry analyses confirmed the disappearance of SG's crystalline and melting peaks, suggesting complexation and amorphization. Meanwhile, solid-state ¹³C CP/MAS NMR and near-infrared spectroscopy revealed chemical shift alternation and peak broadening in C-H and carbon signals. This demonstrates clear molecular interactions and differences in inclusion modes between the SG and the host materials. In solubility tests using fasted-state simulated intestinal fluid, EVP (SG/γCD = 1/2) and EVP (SG/CD-MOF-1 = 1/2) significantly increased in SG solubility by approximately 194-fold and 193-fold, respectively, compared with intact SG. Both complexes achieved rapid release from the early stages of testing. CD-MOF-1 showed unique dissolution behavior attributed to its rigid three-dimensional framework. These findings suggest that forming inclusion complexes with γCD or CD-MOF-1 can enhance the aqueous solubility and dissolution performance of SG, offering promising potential for the development of oral SG formulations.