title: Degradation kinetics of methacrylated dextrans in aqueous solution.
abstract: The kinetics of the hydrolysis of glycidyl methacrylate derivatized dextran (dex-MA), hydroxyethyl methacrylate derivatized dextran (dex-Hema, and hydroxyethyl methacrylate (HEMA) were systematically investigated in aqueous solution in the H0/pH range of -1.8 to 10.4 at 37 degrees C. The degradation products were quantified with reversed-phase HPLC and used to calculate the residual amount of dextran-bound methacrylate esters. In all compounds the degradation reactions follow first-order kinetics, the rate constants being susceptible to both specific acid and specific base catalysis. The reaction rate constant was independent of both the dex-MA concentration and the degree of substitution. The log Kobs-pH profiles can be divided into three parts: a proton-catalyzed, a solvent-catalyzed, and a hydroxyl-catalyzed section. At high acidities, dex-HEMA and HEMA are equally stable, but about seven times less stable than dex-MA. At alkaline pH, the order of stability is HEMA > dex-MA > dex-HEMA. This demonstrates that at alkaline pH dex-HEMA is predominantly degraded by hydrolysis of the carbonate ester, whereas at low pH, hydrolysis of the methacrylate ester is the main degradation route of this compound.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands.
authors.forename: W N
authors.initials: WN
authors.lastname: van Dijk-Wolthuis
authors.forename: M J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: W J
authors.initials: WJ
authors.lastname: Underberg
authors.forename: W E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D002021:Buffers; D003911:Dextrans; D008689:Methacrylates; D012996:Solutions; D014867:Water