Dissolution Behavior of Flufenamic Acid in Heated Mixtures with Nanocellulose

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Nanotechnology

Background:

• Flufenamic acid (FFA) exhibits poor solubility and polymorphism, limiting its oral solid dosage form utility due to variable bioavailability.
• Investigating FFA's solid-state behavior and dissolution is crucial for developing effective drug delivery systems.

Purpose of the Study:

• To explore the polymorphism and amorphization of flufenamic acid (FFA) when mixed with high surface area nanocellulose (Cladophora cellulose, CLAD) and microcrystalline cellulose (MCC).
• To evaluate the dissolution behavior of FFA-cellulose mixtures in biorelevant media after storage.

Main Methods:

• Characterization of solid-state properties using X-ray diffraction, Fourier-transform infrared spectroscopy, and differential scanning calorimetry.
• Dissolution studies in simulated gastric and intestinal fluids (fasted and fed states).
• Assessment of stability after 4 months of storage at 75% relative humidity and room temperature.

Main Results:

• Heated mixtures of FFA with CLAD achieved complete amorphization, while FFA with MCC yielded multiple polymorphs.
• Amorphous FFA-CLAD mixtures demonstrated rapid and consistent dissolution in simulated intestinal fluids, irrespective of fed or fasted state.
• FFA-CLAD mixtures remained stable during storage, showing no recrystallization or dissolution profile changes, unlike FFA-MCC mixtures.

Conclusions:

• Dry powder formulation of FFA with CLAD nanocellulose effectively amorphizes the drug, significantly enhancing dissolution.
• This approach offers a promising strategy for reformulating problematic drugs, improving their solubility and reducing bioavailability fluctuations.
• The stability and consistent dissolution profile of amorphous FFA-CLAD mixtures highlight their potential for oral solid dosage forms.