Effect of antioxidant activity of caffeic acid with cyclodextrins using ground mixture method

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Caffeic acid (CA) is a natural phenolic compound with significant antioxidant properties.
• Cyclodextrins (CDs), specifically α-cyclodextrin (αCD) and β-cyclodextrin (βCD), are widely used to improve the solubility and stability of guest molecules.
• Understanding the complexation behavior of CA with different CDs is crucial for developing advanced delivery systems.

Purpose of the Study:

• To prepare and characterize ground mixtures (GMs) of caffeic acid (CA) with α-cyclodextrin (αCD) and β-cyclodextrin (βCD).
• To comparatively evaluate the physicochemical properties and antioxidant capacities of these CA/CD inclusion complexes.
• To elucidate the structural differences in inclusion complex formation between CA/αCD and CA/βCD.

Main Methods:

• Preparation of ground mixtures (GMs) of CA with αCD and βCD at a 1:1 molar ratio.
• Phase solubility studies to determine complex formation and stoichiometry.
• Stability constant determination.
• Powder X-ray diffraction (PXRD) for structural analysis.
• Dissolution testing to assess release rates.
• ¹H-¹H NOESY NMR spectroscopy to investigate inclusion complex structures.
• DPPH radical-scavenging assay to evaluate antioxidant capacity.

Main Results:

• Phase solubility diagrams confirmed 1:1 complex formation for both CA/αCD and CA/βCD.
• Stability constants indicated higher stability of CA within the αCD cavity compared to βCD.
• PXRD analysis showed the disappearance of characteristic peaks of CA and CDs in the GMs, suggesting complex formation.
• Dissolution rates were significantly enhanced for both CA/αCD and CA/βCD GMs compared to CA alone.
• NMR studies revealed distinct inclusion modes: CA's vinylene group in αCD and aromatic ring in βCD.
• The CA/αCD GM exhibited higher antioxidant capacity than the CA/βCD GM.

Conclusions:

• Caffeic acid forms inclusion complexes with both αCD and βCD, leading to improved dissolution characteristics.
• The stability and antioxidant efficacy of the inclusion complexes are dependent on the type of cyclodextrin used.
• The observed differences in antioxidant capacity are attributed to variations in complex stability and the specific structures of the inclusion complexes formed.