Mechanistic insight into gel-induced aggregation of amorphous curcumin during dissolution process

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Amorphous curcumin (CUR) shows poor dissolution compared to crystalline forms due to gelation.
• Understanding the gelation mechanism is crucial for developing effective amorphous drug formulations.

Purpose of the Study:

• To investigate the mechanism behind amorphous curcumin gelation during dissolution.
• To evaluate the impact of environmental factors and excipients on this phenomenon.

Main Methods:

• Characterization of amorphous CUR gels using TPA, SEM, DSC, XRPD, FTIR, and PLM.
• Assessment of excipient effects (hydrophilic vs. hydrophobic) on gelation and dissolution.
• Contact angle measurements and fluorescence microscopy to study water infiltration.

Main Results:

• Gelation of amorphous CUR involves water infiltration, forming a porous structure in a high-viscosity supercooled liquid state.
• Temperature and pH influence CUR dissolution and gel properties.
• Hydrophilic excipients accelerate gelation, while hydrophobic excipients inhibit it, improving dissolution.
• Hydrophobic excipients hinder water infiltration, preventing gelation.

Conclusions:

• The gelation potential of amorphous materials must be considered in developing high-quality amorphous drug products.
• Excipient selection is critical for controlling amorphous CUR gelation and optimizing dissolution performance.