Structural properties of so-called NSAID-phospholipid-complexes.
Jan Hüsch1, Bercem Dutagaci, Clemens Glaubitz
1Central Laboratory of German Pharmacists, Carl-Mannich-Strasse 20, Eschborn, Germany.
Summary
Drug-phospholipid complexes, intended to reduce gastrointestinal toxicity, primarily form liposomal and micellar structures in aqueous media, not isolated complexes. This challenges the term "NSAID-phospholipid-complex" in physiological contexts.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Physical Chemistry
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause gastrointestinal toxicity.
- NSAID-phospholipid complexes have been proposed to mitigate this toxicity.
- Structural characterization of these complexes is crucial for understanding their behavior.
Purpose of the Study:
- To structurally characterize drug-phospholipid complexes of diclofenac sodium, ibuprofen, and piroxicam with dipalmitoylphosphatidylcholine (DPPC).
- To investigate complex formation in organic solvents and aqueous media after hydration.
- To evaluate the validity of the term "NSAID-phospholipid-complex" in physiological conditions.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy: 1H/2D ROESY NMR in organic solvents, 31P NMR, and MAS 1H/2D NOESY NMR in aqueous media.
- Fourier Transform Infrared (FT-IR) spectroscopy.
- X-ray diffraction.
- Photon Correlation Spectroscopy (PCS).
Main Results:
- In organic solvents, 1:1 drug-phospholipid complexes formed, with diclofenac and ibuprofen interacting with the polar head group via cation-π interactions.
- Upon hydration, liposomal and micellar structures were predominantly observed, rather than isolated complexes.
- Piroxicam showed no significant interaction with DPPC.
Conclusions:
- The term "NSAID-phospholipid-complex" may be misleading for structures formed in physiologically relevant aqueous media.
- Hydration leads to the formation of supramolecular assemblies like liposomes and micelles.
- Diclofenac and ibuprofen interact with DPPC's polar head group in non-aqueous environments.
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