Host-guest complexation of oxicam NSAIDs with beta-cyclodextrin

Area of Science:

• Physical Chemistry
• Materials Science
• Pharmacology

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) of the oxicam class interact with beta-cyclodextrin (beta-cd) for enhanced drug delivery.
• Beta-cyclodextrin (beta-cd) can reduce NSAID gastrointestinal side effects and improve clinical efficacy.
• Understanding host-guest interactions is key to designing advanced drug delivery systems.

Purpose of the Study:

• To resolve the controversy regarding the prototropic form and binding stoichiometry of piroxicam within beta-cyclodextrin.
• To investigate the interactions of tenoxicam and meloxicam with beta-cyclodextrin (beta-cd).
• To elucidate the binding mechanism and stoichiometry of oxicam NSAIDs with beta-cyclodextrin.

Main Methods:

• Steady-state fluorescence spectroscopy
• Absorption spectroscopy
• Fluorescence anisotropy measurements
• Molecular modeling simulations

Main Results:

• Neutral forms of piroxicam, meloxicam, and tenoxicam are incorporated into the beta-cyclodextrin (beta-cd) cavity.
• A 1:1 host:guest stoichiometry was determined for all studied oxicam NSAIDs.
• Binding constants were quantified: piroxicam (134±21 M⁻¹), meloxicam (114±15 M⁻¹), and tenoxicam (115±13 M⁻¹).
• Molecular modeling indicated favorable interactions with drug's conjugated rings within the beta-cd cavity.

Conclusions:

• The neutral forms of oxicam NSAIDs bind to beta-cyclodextrin (beta-cd) in a 1:1 host:guest complex.
• This 1:1 complexation, with drug rings in the beta-cd cavity, supports the design of effective NSAID drug delivery systems.
• The findings clarify previous controversies and establish interaction parameters for piroxicam, meloxicam, and tenoxicam with beta-cyclodextrin.