Interactions between fenoprofen sodium and poly (ethylene oxide)

  • Rades T
  • Mueller-Goymann C
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Abstract

Interactions of the amphiphilic drug fenoprofen sodium (FNa) in solution below and above its critical micelle concentration with poly (ethylene oxide) (PEO) of different chain length (PEO 400 to PEO 20 000) and between a liquid crystalline formulation of fenoprofen (FLC; containing FNa, fenoprofen acid and water) and PEO were investigated, using surface tension measurements, viscometry, cloud point temperature measurements, [1H]NMR, polarised light microscopy, transmission electron microscopy, and differential scanning calorimetry. Interaction between FNa solutions and PEO: the investigations suggest that an interaction starts below the critical micelle concentration (CMC) of FNa. This can be concluded from [1H]NMR experiments (an upfield shift of the PEO proton signal was found at FNa concentrations below the CMC of FNa), surface tension measurements (absence of a critical association concentration) and cloud point temperature determinations. The surfactant does not seem to bind quantitatively on the PEO molecules (a higher FNa concentration was needed to cause the same upfield shift of the PEO proton signal than for more lipophilic surfactants, and no plateau phase in the surface tension reduction isotherm could be determined).Interactions were found to be independent from the chain length of the PEO. Interactions between FLC and PEO/pluronics: partial or complete dissolution of the fenoprofen mesophase (detected by [1H]NMR, polarised light microscopy and transmission electron microscopy) occurred after addition of PEO at concentrations between 2 and 10% (w/w), independent from the molecular weight of the PEO. A comparable amount of water added to the liquid crystalline samples does not change the mesophase into a liquid crystalline dispersion or a micellar solution. The liquid crystalline particles in the dispersion formed by the addition of PEO, had a higher transition temperature into an isotropic phase (between 54°C and 57°C), than in liquid crystalline dispersions without polymer (40°C). The interactions between FNa and PEO can be interpreted in terms of a hydrophobic interaction with an association of the drug molecules on the polymer, i.e. the interaction between FNa and PEO occurs at a molecular rather than a micellar level. The interaction leads to a dissolution of the fenoprofen liquid crystal and the formation of an isotropic phase. No phase separation of the oily, amorphous, practically water insoluble fenoprofen acid could be found. Addition of PEO also seems to affect the composition of the remaining mesophase. Copyright (C) 1998 Elsevier Science B.V.

Author-supplied keywords

  • Differential scanning calorimetry
  • Fenoprofen sodium
  • Polarised light microscopy
  • Poly (ethylene oxide)
  • Surfactant-polymer interactions
  • Transmission electron microscopy

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