Role of Microstructure in Drug Release from Chitosan Amorphous Solid Dispersions

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Amorphous solid dispersions are crucial for enhancing drug solubility and bioavailability.
• The dissolution behavior of amorphous diflunisal-chitosan systems differs unexpectedly from crystalline counterparts.
• Microstructure is often overlooked but vital for understanding drug release from polymeric systems.

Purpose of the Study:

• To investigate the diflunisal release behavior from amorphous solid dispersions using chitosan and carboxymethylchitosan.
• To elucidate the role of microstructure, specifically pore size and tortuosity, in controlling drug release kinetics.
• To compare drug release mechanisms between different polymeric matrices and preparation methods.

Main Methods:

• Preparation of amorphous diflunisal-chitosan and diflunisal-carboxymethylchitosan solid dispersions using the kneading method.
• Characterization of the porous microstructure (pore size, porosity, tortuosity) of the solid dispersions.
• In vitro dissolution testing of diflunisal release kinetics from the prepared systems.
• Analysis of drug release mechanisms (e.g., Fickian diffusion, erosion) using kinetic data.

Main Results:

• Drug release from diflunisal dispersions is primarily governed by the porous structure, which is dependent on the preparation method.
• Amorphous kneaded products with low mean pore size (1-2 μm), low porosity, and high tortuosity exhibited slow diflunisal release.
• Crystalline co-evaporated systems showed faster release due to larger pore size (8-10 μm) and lower tortuosity.
• Diflunisal-carboxymethylchitosan products displayed similar microstructures and overlapping dissolution profiles, with erosion contributing significantly to release.
• Fickian diffusion was the dominant release mechanism for diflunisal from chitosan systems.

Conclusions:

• The porous microstructure, determined by the preparation method, is the key factor controlling diflunisal release from amorphous solid dispersions.
• Differences in pore size, porosity, and tortuosity explain the varying release rates between amorphous kneaded and crystalline co-evaporated systems.
• The solubility of carboxymethylchitosan contributes to an erosion-based drug release mechanism, distinct from the Fickian diffusion observed in chitosan systems.