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.