title: Long-term stability of quercetin nanocrystals prepared by different methods.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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°C) and at room temperature (25±2°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°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.
authors.affiliation: School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.
authors.forename: Mitali
authors.initials: M
authors.lastname: Kakran
authors.forename: Ranjita
authors.initials: R
authors.lastname: Shegokar
authors.forename: Nanda Gopal
authors.initials: NG
authors.lastname: Sahoo
authors.forename: Sven
authors.initials: S
authors.lastname: Gohla
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D011232:Chemical Precipitation; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D053758:Nanoparticles; D010316:Particle Size; D011794:Quercetin / Q000737:chemistry*; D012034:Refrigeration; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D000975:Antioxidants; D012997:Solvents; D011794:Quercetin