Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation

Although myricetin has various pharmacological applications, it shows low oral bioavailability (<10%) in rats due to its poor aqueous solubility. To overcome this issue, myricetin nanosuspensions were developed and the effects of stabilizers were investigated. Based on the particle size and zeta potential, stabilizers soya lecithin, TPGS, HP-beta-CD, and/or a combination thereof were used. The prepared nanosuspensions were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD). The resulting myricetin nanosuspensions contained particles in the size range of 300-500 nm and were physically stable. Myricetin was partially transformed from crystalline to amorphous forms in the presence of different excipients after the nanosizing process. The solubility and in vitro dissolution of all myricetin nanosuspensions were greatly increased compared with those of the myricetin powder. Consequently, the relative bioavailability in rats were 2.44, 3.57, 1.61, and 2.96 for nanosuspensions stabilized with TPGS, soya lecithin, soya lecithin +TPGS, and HP-beta-CD+TPGS, respectively, relative to that of the coarse myricetin. This research demonstrated that nanosuspension is a promising strategy for delivering poor water-soluble drugs such as myricetin and that stabilizers played a critical role in the formulation design of myricetin nanosuspensions. (C) 2014 Elsevier B.V. All rights reserved.