Long-term stability of quercetin nanocrystals prepared by different methods

Objectives This study aimed to examine the long-term physical stability of quercetin nanocrystals produced by three methods. Methods Quercetin nanocrystals were prepared by high pressure homogenization, bead milling and cavi-precipitation. The nanocrystals produced by these methods were compared for particle size, saturation solubility and dissolution of the drug particles, and were subjected to stability testing. Key findings The X-ray diffraction study and microscopic pictures taken under polarized light indicated the crystalline nature of the nanocrystals produced by the three methods. As the crystalline state is relatively more stable than the amorphous state, a good physical stability was expected from the quercetin nanocrystals prepared. The high-pressure homogenized and bead-milled quercetin nanocrystals showed excellent physical stability when stored under refrigeration (4 +/- 2 degrees C) and at room temperature (25 +/- 2 degrees C) for 180 days. The dissolution properties were not significantly affected on storage at room temperature. However, increase in the storage temperature to 40 +/- 2 degrees C led to physical instability. On the other hand, the cavi-precipitated quercetin nanocrystals exhibited a lower stability than the bead-milled and homogenized formulations and did not show the optimum zeta potential values as well. In the case of cavi-precipitated nanocrystals, recrystallization and agglomeration were responsible for the increasing particle size besides the Ostwald ripening phenomenon. The solvents used during cavi-precipitation might have competed with the surfactant for hydration leading to a partial dehydration of the surfactant, which subsequently affected the stability of the quercetin nanocrystals. Conclusions High-pressure homogenized and bead-milled quercetin nanocrystals showed better physical stability than the cavi-precipitated ones. Freeze drying immediately after nanocrystal production can help to prevent their agglomeration and thus improve physical stability.