Evidence for solid- and liquid-state interactions in a furosemide-polyvinylpyrrolidone solid dispersion.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Solid dispersions enhance drug solubility and bioavailability.
• Understanding drug-excipient interactions is crucial for stable formulations.
• Furosemide (FUR) is a diuretic with poor aqueous solubility.

Purpose of the Study:

• To investigate solid-state interactions between furosemide (FUR) and polyvinylpyrrolidone (PVP).
• To elucidate the role of hydrogen bonding in the stabilization of amorphous FUR-PVP solid dispersions.
• To correlate solution and solid-state interaction data.

Main Methods:

• Fourier Transform Infrared (FTIR) spectroscopy with spectral subtraction.
• Proton Nuclear Magnetic Resonance (NMR) spectroscopy.
• Molecular graphics and computational analysis of crystal structure.

Main Results:

• FTIR revealed shifts in FUR-NH stretching vibrations in amorphous FUR-PVP, indicating interactions.
• NMR studies showed concentration and temperature-dependent shifts in FUR sulfonamide proton resonance, consistent with hydrogen bonding.
• Analysis suggested preferential binding of the FUR sulfonamide group to PVP via hydrogen bonds.

Conclusions:

• Hydrogen bonding between the furosemide sulfonamide group and polyvinylpyrrolidone is confirmed.
• These interactions are key to the formation and stabilization of amorphous solid dispersions.
• The findings provide insights into optimizing drug formulation for enhanced delivery.