Amino Acid Salt-Based Co-Amorphous Systems of Curcumin Mechanistic Insights and Strategies for Enhanced Solubility and Bioavailability

Abstract

Curcumin, a hydrophobic polyphenol derived from Curcuma longa, exhibits diverse pharmacological activities including antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Despite its therapeutic potential and safety, curcumin’s clinical translation remains limited due to its poor aqueous solubility, low intestinal absorption, rapid metabolism, and extremely low oral bioavailability. Conventional strategies such as polymer-based solid dispersions, nanoparticles, and cyclodextrin complexes have improved solubility but face limitations related to high excipient load, stability, and scalability. Co-amorphous systems (CAMS), composed of curcumin and low-molecular-weight co-formers such as amino acid salts, have emerged as a promising alternative. Amino acids including L-arginine, lysine, and tryptophan serve as effective co-formers owing to their ability to form hydrogen bonds, ionic interactions, and hydrophobic or aromatic contacts with curcumin. These interactions disrupt crystalline packing, enhance the glass transition temperature, and suppress recrystallization, thereby stabilizing the amorphous phase. As a result, curcumin–amino acid CAMS exhibit markedly improved solubility, dissolution rate, and bioavailability compared to crystalline curcumin. Preparation techniques such as liquid-assisted grinding, solvent evaporation, spray drying, hot-melt extrusion, and supercritical fluid processing have demonstrated feasibility at both laboratory and industrial scales. Furthermore, in vitro and in vivo studies confirm that amino acid-based CAMS improve pharmacological performance without compromising safety. In conclusion, amino acid salt-based co-amorphous systems represent a scalable and biocompatible strategy to enhance curcumin delivery, offering significant potential for future clinical translation.