Gelation Elimination and Crystallization Inhibition by Co-Amorphous Strategy for Amorphous Curcumin

In the previous study, the development of amorphous curcumin (CUR) aimed to enhance the solubility/dissolution of CUR by disrupting its crystal lattice, but it unexpectedly showed a decreased dissolution than its crystalline counterpart on account of gel formation in its dissolution process. Whether such gelation could be eliminated by co-amorphous strategy was answered in this study. Herein, CUR by co-amorphization with chlorogenic acid (CHA) was successfully prepared using quench cooling. The formed co-amorphous material (namely CUR-CHA CM) eliminated the gelation and hence performed superior dissolution performance than crystalline/amorphous CUR. Meanwhile, it exhibited higher physical stability than amorphous CUR during dissolution as well as under long-term/accelerated conditions. To further study the such enhancement mechanism, the internal molecular interactions were investigated for CUR-CHA CM in the solid state as well as in aqueous solution. FTIR and solid-state ¹³C NMR spectra confirmed that intermolecular hydrogen bonds formed between CUR and CHA after co-amorphization. Furthermore, the nucleation of CUR was significantly inhibited by CHA in an aqueous solution, thus maintaining the supersaturated dissolution for a long time. The present study offers a feasible strategy to eliminate gelation and enhance stability of amorphous solids by co-amorphization and crystallization inhibition.