title: The fate of free radicals in a cellulose based hydrogel: detection by electron paramagnetic resonance spectroscopy.
abstract: Cellulose derivatives are commonly used as gelling agents in topical and ophthalmic drug formulations. During the course of manufacturing, cellulose derivatives are believed to generate free radicals. These free radicals may degrade the gelling agent, leading to lower viscosity. Free radicals also may react with the active ingredient in the product. The formation of radicals in a 3% hydrogel of hypromellose (hydroxypropyl methylcellulose) was monitored by electron paramagnetic resonance (EPR) spectroscopy and spin trapping techniques. Radicals were trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and quantitated by comparing the EPR intensity with 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL), a stable free radical. Typically, the hydrogels showed an initial increase in the radical concentration within 2 days after autoclaving, followed by a drop in radical concentration in 7 days. EDTA prevented the formation of free radicals in the hypromellose (HPMC) hydrogel, suggesting the involvement of metal ions in the generation of free radicals. The oxidizing potential of the hydrogel was estimated by measuring the rate at which methionine (a model for the protein active pharmaceutical ingredient) was degraded, and was consistent with the amount of radicals present in the gel. This study is the first report investigating the application of EPR spectroscopy in detecting and estimating free radical concentration in cellulose based hydrogels.
authors.affiliation: Department of Late Stage Pharmaceutical and Device Development, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Lipika
authors.initials: L
authors.lastname: Basumallick
authors.forename: J Andrea
authors.initials: JA
authors.lastname: Ji
authors.forename: Nariman
authors.initials: N
authors.lastname: Naber
authors.forename: Y John
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D003497:Cyclic N-Oxides; D004492:Edetic Acid / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005609:Free Radicals / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D065347:Hypromellose Derivatives; D008715:Methionine / Q000378:metabolism; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
chemical_list: D003497:Cyclic N-Oxides; D005609:Free Radicals; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D065347:Hypromellose Derivatives; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D008747:Methylcellulose; D004492:Edetic Acid; D008715:Methionine