Structural properties of so-called NSAID–phospholipid-complexes

Abstract

So-called NSAID–phospholipid-complexes have been recently reported in literature to reduce local gastrointestinal toxicity. The present work was dedicated to the structural characterization of so-called drug–phospholipid-complexes on the example of diclofenac sodium, ibuprofen and piroxicam complexes with dipalmitoylphosphatidylcholine (DPPC) at different stages of preparation. The applied techniques include 1H/2D ROESY NMR for the structural characterization in organic solvents, FT-IR and X-ray diffraction for the structural characterization in the solid state and PCS, 31P NMR, as well as MAS 1H/2D NOESY NMR for the structural characterization in aqueous media following hydration. Whereas the formation of isolated 1:1 drug–phospholipid-complexes with a preferential location of diclofenac and ibuprofen at the polar head group, stabilized by cation-π interaction, seems reasonable in organic solvents, it was found that mainly liposomal and micellar structures are formed upon hydration of the drug–phospholipid-complexes. Hence the term “NSAID–phospholipid-complex” may be misleading in the context with physiologically relevant aqueous media. Piroxicam did not show significant interaction with DPPC.