Composite formation of alpha-lipoic acid and quercetin by reverse drowning-out crystallization

Patients often face difficulty taking more than one drug at once to treat a disease. A drug composite of alpha-lipoic acid (ALA) for blood sugar control and quercetin (QU) with antioxidant properties can improve patient convenience. Drug composites also offer advantages in stability, efficiency, and controlled release. In this study, ALA–QU composites were prepared by reverse drowning-out crystallization. The drug solution was injected into an antisolvent to induce rapid supersaturation and crystallization. Crystal formation was confirmed by polarized optical microscopy (OM). OM images showed that the ALA–QU composite had a different crystal morphology from the single ALA and QU crystals, indicating that the two drugs crystallized together rather than forming only individual crystals. X-ray diffraction (XRD) analysis showed changes in the characteristic diffraction peaks of ALA and QU, confirming that the crystallinity of the obtained solid was changed after composite formation. Nuclear magnetic resonance (NMR) spectroscopy further confirmed that both ALA and QU were included in the final solid composite. These results suggest that the ALA–QU composite has the potential to improve drug performance as a multi-drug formulation.