Design, Development, and Characterization of High Drug-Loaded Drug-Drug-Polymer Ternary Amorphous Solid Dispersions.

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Conventional amorphous solid dispersions (ASD) face limitations.
• Ternary amorphous solid dispersions (TASD) offer improved properties.
• Combining multiple poorly water-soluble drugs presents formulation challenges.

Purpose of the Study:

• To design, characterize, and evaluate a stable, high drug-loaded TASD.
• To combine two poorly water-soluble drugs, curcumin (CUR) and resveratrol (RES), using a hydrophilic polymer.
• To assess the impact of TASD formulation on drug solubility and stability.

Main Methods:

• Extensive polymer screening including miscibility, crystallization tendency, and interaction parameters.
• Preparation of TASD via rotary evaporation.
• Characterization using XRD, DSC, TGA, FTIR, and Raman spectroscopy.
• In-vitro dissolution studies under non-sink conditions and long-term physical stability assessment.

Main Results:

• Eudragit EPO identified as the optimal polymer.
• High drug-loaded (50% w/w) TASD was successfully prepared, exhibiting amorphous nature and strong drug-polymer interactions.
• Significant enhancement in dissolved CUR (~197-fold) and RES (~4-fold) compared to physical mixtures.
• TASD formulation remained physically amorphous for 12 months at room temperature.

Conclusions:

• TASD formulation with Eudragit EPO provides a stable and highly soluble system for poorly water-soluble drugs CUR and RES.
• The developed TASD demonstrates superior dissolution performance compared to binary ASDs and physical mixtures.
• This approach holds promise for improving the bioavailability of challenging drug combinations.