| DOI: 10.29090/psa.2025.03.25.5007 | Pharm Sci Asia 2025; 52(3), 362-375 |
Preparation, characterization, and antioxidant capacity of rosmarinic acid inclusion complexes into γ-cyclodextrinAkiteru Ohtsu1, Mione Uchimura1, Nao Kodama1, Shun-ichi Mitomo1, Junki Tomita2, Mitsuaki Suzuki3, and Yutaka Inoue1*
1 Laboratory of Nutri-Pharmacotherapeutics Management, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 3500295, Japan
2
Instrument Analysis Center, Josai University, 1-1 Keyakidai, Sakado, Saitama 3500295, Japan
3
Department of Chemistry & Biological Science, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 3500295, Japan
The purpose of this study was to prepared inclusion complexes of rosmarinic acid (RA) with γ-cyclodextrin (γ-CD) and cyclodextrin-metal–organic framework (CD-MOF) were prepared as ground mixtures (GMs) using a three-dimensional grinding method. The physicochemical properties, intermolecular interactions, solubility, and antioxidant capacity of GM (RA/γ-CD) and GM (RA/CD-MOF-1) were evaluated. Powder X-ray diffraction analysis demonstrated the disappearance of diffraction peaks in GM (γ-CD/RA = 1/1, RA/CD-MOF-1 = 1/1), suggesting that RA transformed into an amorphous state upon complexation. Differential scanning calorimetry analysis revealed that the endothermic peak of RA (~170°C), corresponding to its melting point, was absent from these complexes, indicating inclusion complex formation. Near-infrared spectroscopy exhibited peak shifts in the -CH stretching vibrations of RA, -OH groups of γ-CD, and absorption bands associated with free water, suggesting intermolecular interactions within the complexes. Dissolution tests (5 min) showed that RA had ~70% solubility, whereas the solubility of GM (RA/γ-CD) and GM (RA/CD-MOF-1) increased to ~85% and ~95%, respectively. 1H-1H nuclear Overhauser effect nuclear magnetic resonance spectroscopy detected cross-peaks between RA protons (H-A to H-E, H-A? to H-C??) and γ-CD cavity protons (H-6 at 3.6 ppm, H-3 at 3.7 ppm) in GM (RA/γ-CD), confirming encapsulation. Similarly, GM (RA/CD-MOF-1) interacted with H-6 (3.65 ppm), suggesting inclusion of RA. Antioxidant assays showed marginal half-maximal inhibitory concentration improvement compared with that of RA alone (1.72 μg/mL). CD-MOF inclusion complexes show potential as platforms for improving the drug bioavailability and bioactivity in pharmaceutical formulations. These findings suggest that CD-MOF-1-based inclusion complexes could be valuable platforms for enhancing solubility and functional performance of phenolic compounds like RA in pharmaceutical applications.
Keyword:
Rosmarinic acid; Cyclodextrin; Physicochemical property; NOESY NMR spectroscopy; Antioxidant
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