Inclusion Complexes of Stearyl Glycyrrhetinate with γ‑Cyclodextrin and Cyclodextrin-Based Metal-Organic Frameworks:...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Stearyl glycyrrhetinate (SG) is a poorly water-soluble derivative of glycyrrhetinic acid, limiting its oral bioavailability.
• Enhancing the solubility and dissolution of poorly soluble drugs is crucial for developing effective oral formulations.

Purpose of the Study:

• To formulate stearyl glycyrrhetinate (SG) into inclusion complexes with gamma-cyclodextrin (γCD) and cyclodextrin-based metal-organic frameworks (CD-MOF-1).
• To evaluate the impact of these inclusion complexes on the solubility, dissolution, and solid-state properties of SG.

Main Methods:

• Solid-state complexation using the evaporation method (EVP).
• Characterization of inclusion complexes using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), solid-state ¹³C CP/MAS NMR, and Near-Infrared (NIR) spectroscopy.
• Solubility and dissolution testing in fasted-state simulated intestinal fluid.

Main Results:

• PXRD and DSC confirmed complexation and amorphization of SG within both γCD and CD-MOF-1.
• Spectroscopic analyses (¹³C CP/MAS NMR and NIR) indicated molecular interactions and distinct inclusion modes.
• Solubility of SG increased approximately 194-fold with γCD and 193-fold with CD-MOF-1.
• Both complexes exhibited rapid drug release, with CD-MOF-1 showing unique dissolution behavior.

Conclusions:

• Formation of inclusion complexes with γCD and CD-MOF-1 significantly enhances the aqueous solubility and dissolution rate of stearyl glycyrrhetinate.
• These findings highlight the potential of γCD and CD-MOF-1 as effective carriers for improving oral formulations of poorly soluble drugs like SG.