Amorphous nanoparticles by self-assembly: processing for controlled release of hydrophobic molecules

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Over 40% of new drugs are hydrophobic, leading to poor bioavailability.
• Amorphous nanoparticles enhance drug solubility, but recrystallization during drying reduces effectiveness.
• Hydrophobic drugs like lumefantrine (anti-malarial) require improved delivery for better patient outcomes.

Purpose of the Study:

• To develop a continuous platform combining Flash NanoPrecipitation (FNP) and spray-drying for stable amorphous drug nanoparticles.
• To assess the impact of spray-drying temperature on the amorphous state and dissolution kinetics of lumefantrine nanoparticles.
• To evaluate the potential of this platform for creating cost-effective malaria therapies.

Main Methods:

• Synthesized lumefantrine nanoparticles (200-400 nm) using FNP with stabilizers (HPMCAS, lecithin, zein).
• Spray-dried zein nanoparticles at 100 °C and 120 °C to evaluate drying temperature effects.
• Characterized nanoparticle amorphous state and dissolution using Powder X-ray Diffraction, Differential Scanning Calorimetry, and Solid State Nuclear Magnetic Resonance.

Main Results:

• Spray-drying at 100 °C maintained the amorphous state of lumefantrine nanoparticles, achieving 85% release in 2 hours (fasted state).
• Drying at 120 °C led to partial recrystallization, reducing release to 60% under fasted conditions.
• Both spray-drying temperatures resulted in 90-95% release within 2 hours under fed state conditions.
• Formulations dried at 100 °C showed dissolution profiles identical to lyophilized controls.

Conclusions:

• Spray-drying lumefantrine nanoparticles 30 °C below their melting point (100 °C) effectively preserves the amorphous state.
• The combined FNP and spray-drying platform offers a versatile method for producing stable amorphous nanoparticles in a solid dosage form.
• This approach holds promise for developing improved, cost-effective malaria treatments and other therapies for hydrophobic drugs.