Formulation of Nanoparticle Containing Everolimus Using Microfluidization and Freeze-Drying

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Poorly water-soluble drugs like everolimus (EVR) present challenges in achieving adequate bioavailability.
• Traditional methods for improving solubility often involve organic solvents, posing environmental and safety concerns.

Purpose of the Study:

• To enhance the in vitro dissolution of everolimus (EVR) without using organic solvents.
• To characterize the effects of microfluidization and freeze-drying on the physicochemical properties of EVR nanosuspensions and nanoparticles.
• To evaluate the impact of stabilizers and cryoprotectants on EVR nanoparticle characteristics and performance.

Main Methods:

• Everolimus (EVR) nanosuspension preparation via microfluidization with various stabilizers (e.g., poloxamer 407).
• Solidification into nanoparticles using freeze-drying with varying concentrations of xylitol as a cryoprotectant.
• Characterization of particle size, zeta potential, physical stability, and chemical stability.
• In vitro drug release studies comparing nanoparticles with a physical mixture.

Main Results:

• Poloxamer 407 at 0.5% (w/w) was identified as an optimal stabilizer for EVR nanosuspension based on particle size, zeta potential, and yield.
• Freeze-drying with 1% (w/w) xylitol significantly improved both physical and chemical stability of the EVR nanoparticles.
• In vitro release testing demonstrated a markedly improved dissolution profile for the EVR nanoparticles compared to a physical mixture.

Conclusions:

• Microfluidization and freeze-drying offer a viable solvent-free approach for developing stable everolimus (EVR) nanoparticles.
• The optimized formulation exhibits enhanced dissolution properties, indicating potential for improved in vivo bioavailability.
• This method provides a promising strategy for formulating other poorly water-soluble drugs.