Solubilization and interaction of sulindac with beta-cyclodextrin in the solid state and in aqueous solution

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Sulindac is a non-steroidal anti-inflammatory drug (NSAID).
• Beta-cyclodextrin (beta-CD) is a cyclic oligosaccharide used to improve drug properties.
• Drug complexation with cyclodextrins can enhance solubility and stability.

Purpose of the Study:

• To prepare and characterize a sulindac-beta-cyclodextrin complex.
• To evaluate the solid-state interactions and stability of the complex.
• To assess the impact of complexation on sulindac's dissolution rate and solubility.

Main Methods:

• Coprecipitation method for complex formation.
• X-ray powder diffraction (XRPD) for crystallinity analysis.
• Differential scanning calorimetry (DSC) for thermal analysis.
• Dissolution rate studies.
• UV-Vis spectroscopy for solution interactions.
• Stability constant determination at various pH and temperatures.

Main Results:

• The coprecipitated sulindac-beta-cyclodextrin complex was noncrystalline, unlike pure sulindac and other systems.
• DSC confirmed solid-state interaction between sulindac and beta-CD.
• The complex remained stable after one year of storage.
• Enhanced dissolution rate and increased apparent solubility of sulindac were observed.
• Stability constants indicated temperature-dependent complex stability and preferential binding to non-ionized sulindac.

Conclusions:

• Coprecipitation effectively formed a stable, noncrystalline sulindac-beta-cyclodextrin complex.
• Complexation significantly improved sulindac's dissolution and solubility.
• The study highlights the potential of beta-cyclodextrin for enhancing sulindac's pharmaceutical properties.