Spectroscopic investigation on the inclusion complex formation between amisulpride and γ-cyclodextrin

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Supramolecular Chemistry

Background:

• Amisulpride (AMI) is a poorly soluble antipsychotic drug.
• Enhancing drug solubility is crucial for improving bioavailability and therapeutic efficacy.
• Cyclodextrins, like gamma-cyclodextrin (γ-CD), are widely used to improve the solubility of hydrophobic drugs.

Purpose of the Study:

• To investigate the formation of an inclusion complex between amisulpride (AMI) and gamma-cyclodextrin (γ-CD).
• To characterize the inclusion complex and determine its stoichiometry and binding affinity.
• To evaluate the effect of complexation on the solubility of amisulpride.

Main Methods:

• Solubility studies were performed to assess the impact of γ-CD complexation on AMI solubility.
• Continuous variation Job's plot and Benesi-Hildebrand methods were employed to determine the complex stoichiometry and binding constant.
• Molecular docking simulations were utilized to predict the binding mode and interactions within the inclusion complex.
• Spectroscopic and thermal analyses, including (1)H NMR, FT-IR, DSC, and XRD, were used to confirm complex formation.

Main Results:

• The stoichiometry of the amisulpride-γ-cyclodextrin inclusion complex was determined to be 1:1.
• The binding constant for the inclusion complex was calculated to be 1166.65 M(-1).
• Molecular docking provided insights into the molecular interactions driving complex formation.
• Spectroscopic and thermal analyses confirmed the formation of the inclusion complex.
• The solubility of amisulpride was enhanced by a factor of 3.74 upon complexation with γ-CD.

Conclusions:

• Gamma-cyclodextrin effectively forms a 1:1 inclusion complex with amisulpride.
• Complexation with γ-CD significantly enhances the aqueous solubility of amisulpride.
• The developed inclusion complex holds potential for improving the formulation and delivery of amisulpride.