Triethanolamine stabilization of methotrexate-β-cyclodextrin interactions in ternary complexes.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Supramolecular Chemistry

Background:

• Methotrexate (MTX) is a crucial chemotherapeutic agent with limited solubility.
• Beta-cyclodextrin (β-CD) is a known host molecule for drug complexation.
• Triethanolamine (TEA) can potentially modify cyclodextrin complexation.

Purpose of the Study:

• To investigate the ternary complexation mechanism of MTX with β-CD in the presence of TEA.
• To elucidate the role of TEA in stabilizing the MTX:β-CD complex.
• To evaluate the impact of this ternary complex on MTX solubility, stability, and dissolution.

Main Methods:

• Solubility diagram studies.
• 2D ROESY NMR spectroscopy.
• Molecular modeling.
• FTIR, DSC, TG/DTG, CHN analysis, and XRD studies.
• In vitro drug dissolution studies.

Main Results:

• A synergistic thirty-fold increase in MTX solubility was observed.
• Molecular modeling and ROESY confirmed MTX aromatic ring inclusion into β-CD cavity.
• TEA was found to intensify MTX-β-CD interaction and stabilize the ternary complex via electrostatic interactions.
• Solid-state analyses confirmed the maintenance of MTX-β-CD interactions and enhanced drug stability in the ternary complex.
• In vitro dissolution studies demonstrated significantly improved MTX release from the ternary complex.

Conclusions:

• The MTX:β-CD:TEA ternary complexation significantly enhances MTX solubility and stability.
• TEA plays a critical role in stabilizing the complex through electrostatic interactions.
• This ternary system represents a promising new material for advanced drug delivery applications.