title: Solid-State and Solution Characterization of Myricetin.
abstract: Myricetin (MYR) is a natural compound that has been investigated as a chemopreventative agent. MYR has been shown to suppresses ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) protein expression and reduce the incidence of UVB-induced skin tumors in mice. Despite MYR's promise as a therapeutic agent, minimal information is available to guide the progression of formulations designed for future drug development. Here, data is presented describing the solid-state and solution characterization of MYR. Investigation into the solid-state properties of MYR identified four different crystal forms, two hydrates (MYR I and MYR II) and two metastable forms (MYR IA and MYR IIA). From solubility studies, it was evident that all forms are very insoluble (<5 μg/ml) in pure water. MYR I was found to be the most stable form at 23, 35, and 56°C. Stability determination indicated that MYR undergoes rapid apparent first-order degradation under basic pH conditions, and that degradation was influenced by buffer species. Apparent first-order degradation was also seen when MYR was introduced to an oxidizing solution. Improved stability was achieved after introducing 0.1% antioxidants to the solution. MYR was found to have good stability following exposure to ultraviolet radiation (UVR), which is a consideration for topical applications. Finally, a partitioning study indicated that MYR possess a log P of 2.94 which, along with its solid-state properties, contributes to its poor aqueous solubility. Both the solid-state properties and solution stability of MYR are important to consider when developing future formulations.
authors.affiliation: College of Pharmacy, University of Arizona, P.O Box 210202, Tucson, AZ, 85721, USA. franklin@pharmacy.arizona.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Franklin
authors.affiliation: College of Pharmacy, University of Arizona, P.O Box 210202, Tucson, AZ, 85721, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D005419:Flavonoids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D012995:Solubility; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
chemical_list: D005419:Flavonoids; D019999:Pharmaceutical Solutions; D014867:Water; C040015:myricetin
keywords: hydrate; log P; myricetin; solubility; stability