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Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
Published on: August 15, 2016
Density functional calculations on meloxicam-beta-cyclodextrin inclusion complexes.
Walter Snor1, Elisabeth Liedl, Petra Weiss-Greiler
1Institute of Theoretical Chemistry, University of Vienna, Währinger Strasse 17, A-1090 Wien, Austria.
International Journal of Pharmaceutics
|May 19, 2009
Summary
The study investigated cyclodextrin (CD) inclusion complexes with meloxicam tautomers. The anionic meloxicam form showed the highest affinity for beta-cyclodextrin, indicating preferred complexation for drug delivery applications.
Area of Science:
- Computational Chemistry
- Supramolecular Chemistry
- Pharmacology
Background:
- Cyclodextrins (CDs) are widely used to improve drug solubility and stability.
- Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), exhibits complexation behavior with cyclodextrins.
- Understanding the interaction between meloxicam tautomers and cyclodextrins is crucial for optimizing drug formulations.
Purpose of the Study:
- To determine the preferred geometries and interaction energies of cyclodextrin inclusion complexes with various meloxicam tautomers.
- To investigate the influence of meloxicam's tautomeric form and orientation on complexation with beta-cyclodextrin.
- To establish an affinity ranking for different meloxicam tautomers within the cyclodextrin cavity.
Main Methods:
- Density Functional Theory (DFT) calculations using the B3LYP/6-31G (d,p) basis set were employed.
- Interaction energies were calculated, incorporating basis set superposition error (BSSE) correction.
- Two distinct orientations of meloxicam within the cyclodextrin cavity were analyzed.
Main Results:
- All analyzed meloxicam tautomers were found to reside within the cyclodextrin cavity.
- The preferred complexation orientation involves the meloxicam benzene ring interacting with the wider rim of beta-cyclodextrin, near secondary hydroxyl groups.
- The stabilization energy ranking indicated the following affinity order: anionic > zwitterionic ≈ enolic > cationic.
- The zwitterionic form showed enhanced stabilization over the enolic form due to additional hydrogen bonds.
Conclusions:
- The anionic form of meloxicam exhibits the strongest interaction with beta-cyclodextrin.
- Complexation is favored when the meloxicam molecule is oriented towards the wider rim of the cyclodextrin.
- These findings provide valuable insights into the molecular interactions governing meloxicam-cyclodextrin complexation, aiding in the design of improved drug delivery systems.
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