Lyophilization of Curcumin-Loaded Lipodisks; pre- and post-processing evaluation of formulation characteristics

• Lipodisks tend to fuse and increase in size upon freeze-drying in the absence of cryoprotectant. • Trehalose is more effective than lactose and sucrose in preventing lyophilization-induced size changes. • Freeze-drying in the presence of 5% trehalose allows preservation of structural integrity and functional properties of curcumin-loaded lipodisks. Lipid-based drug delivery systems offer a promising strategy to overcome limitations of conventional anti-cancer therapies. Among these, polyethylene glycol (PEG)-stabilized lipodisks have shown high potential for encapsulating hydrophobic drugs like curcumin. Despite the structural stability of lipodisks, the curcumin formulations face challenges with drug degradation, primarily due to residual drug in the aqueous phase. Lyophilization is a widely used strategy to enhance formulation stability and shelf life, often employing disaccharides as cryoprotectants. However, limited research exists on the lyophilization of lipodisks. This study investigates the effects of lyophilization on the morphology, drug loading, and release kinetics of curcumin-loaded lipodisks prepared via dual centrifugation. Lipodisks were freeze-dried in the absence of cryoprotectant, as well as in the presence of lactose, sucrose, or trehalose. Post-lyophilization analysis revealed that curcumin loading was preserved, though particle size tended to increase. Trehalose was most effective in minimizing fusion and size enlargement of the disks. In vitro release studies confirmed that neither freeze-drying nor rehydration adversely affected the drug release profiles. These findings support trehalose-assisted lyophilization as a viable strategy to enhance the long-term stability of curcumin-loaded lipodisks, reinforcing their potential for clinical translation.