Investigating miscibility and molecular mobility of nifedipine-PVP amorphous solid dispersions using solid-state NMR...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Amorphous solid dispersions enhance drug solubility and bioavailability.
• Understanding miscibility is crucial for drug formulation stability.
• Solid-state Nuclear Magnetic Resonance (SSNMR) is a powerful tool for characterizing amorphous systems.

Purpose of the Study:

• To evaluate the miscibility of nifedipine (NIF) and polyvinylpyrrolidone (PVP) amorphous solid dispersions.
• To compare the impact of different preparation methods (melt quenching, spray drying) on miscibility.
• To determine the domain size and molecular mobility of the dispersions.

Main Methods:

• Solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy was employed.
• (1)H T1 and T1ρ relaxation times were measured to assess miscibility.
• Variable-temperature SSNMR experiments were conducted to probe molecular mobility.

Main Results:

• Miscibility of NIF:PVP amorphous solid dispersions depended on composition and preparation method.
• Lab-prepared melt-quenched dispersions showed miscibility at NIF:PVP ratios of 75:25, 60:40, and 50:50.
• Spray-dried and NMR rotor melt-quenched dispersions (90:10 NIF:PVP) were also found to be miscible.
• Miscible systems had domain sizes < 4.5 nm.
• Increased molecular mobility was observed approximately 20 °C below the glass transition temperature (Tg).

Conclusions:

• SSNMR (1)H T1ρ relaxation is effective for determining the miscibility of NIF:PVP amorphous solid dispersions.
• Preparation method significantly influences the miscibility of amorphous solid dispersions.
• Understanding molecular mobility relative to Tg is important for predicting formulation performance.