title: Preformulation studies of myricetin: a natural antioxidant flavonoid.
abstract: Myricetin is a natural flavonoid which has attracted great interest due to its antioxidant and free-radical scavenging activities. Unfortunately, physicochemical properties of myricetin are largely unknown so far and this would impair the design and development of myricetin formulations. In this paper, a series of studies were performed to investigate physicochemical properties of myricetin, such as its solubility in aqueous/organic solvents, aqueous solubility with different solubilizers, buffers and pHs, dissociation constant (pKa), partition coefficients of log P and log D at various pHs, intrinsic dissolution rate (IDR), and its stability at different temperatures and pHs. The results demonstrated that myricetin is a lipophilic compound with low water solubility but higher solubility in organic solvents or use of solubilizers. Myricetin is also a weak acidic compound with a pKa of 6.63 +/- 0.09, low IDR of 11.66 +/- 0.82 microg/min/cm2 at 37 degrees C. It is most stable at a pH of 2.0 and the degradation of myricetin is both temperature and pH dependent. Therefore, enhancement of the aqueous solubility and dissolution rate of myricetin and prevention from its rapid degradation at high pH and temperature should be considered for further formulation development of myricetin. In summary, these data will be used as rational support to create an efficacious formulation for the delivery of myricetin.
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yashu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Guobei
authors.initials: G
authors.lastname: Lin
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Global Pharmaceutical Research and Development, Hospira Inc., Kansas, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Guowen
authors.initials: G
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Qianchao
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
mesh_terms: D000465:Algorithms; D000975:Antioxidants / Q000737:chemistry*; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D000975:Antioxidants; D002021:Buffers; D005419:Flavonoids; D012997:Solvents; C040015:myricetin