Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Area of Science:

• Pharmaceutics
• Materials Science

Background:

• Amorphous solid dispersions (ASDs) are crucial for improving the solubility and bioavailability of poorly soluble drugs.
• Particle size is a critical factor influencing the dissolution rate and stability of ASDs.
• Griseofulvin (GF) is a model drug used to study dissolution behavior in ASD formulations.

Purpose of the Study:

• To investigate the impact of particle size on the dissolution behavior of griseofulvin amorphous solid dispersions (ASDs).
• To evaluate the role of Kollidon® VA 64 as a crystallization inhibitor in GF ASDs of varying particle sizes.
• To determine the optimal combination of particle size reduction and polymer loading for enhanced drug dissolution.

Main Methods:

• Preparation of GF ASDs with varying particle sizes (45-75 μm to 250-355 μm) and Kollidon® VA 64 loadings (0%-50%).
• Dissolution testing to measure final dissolved GF concentration and dissolution rates.
• Surface concentration (Cs) and Avrami kinetics analysis to assess dissolution and recrystallization rates.
• Raman spectroscopy to confirm solid-state recrystallization.

Main Results:

• Both final dissolved GF concentration and dissolution rate were inversely proportional to particle size.
• The smallest GF ASD particles (45-75 μm) exhibited significantly higher solution concentrations compared to the largest particles (250-355 μm).
• GF ASDs with 50% polymer loading in the finest size group showed a 2.7 times higher dissolution rate than the largest group under supersaturating conditions.
• A 30% loading of Kollidon® VA 64 was sufficient to inhibit GF recrystallization.
• Particle size reduction enhanced ASD drug loading by reducing the need for crystallization inhibitors.

Conclusions:

• Particle size reduction is a key strategy for improving the dissolution behavior of griseofulvin amorphous solid dispersions.
• The combination of particle size reduction and effective recrystallization inhibition (e.g., with 30% Kollidon® VA 64) significantly enhances drug dissolution.
• Smaller ASD particles demonstrate faster initial dissolution, which can overcome their potentially higher recrystallization rates, leading to improved overall performance.