Degradation kinetics of methacrylated dextrans in aqueous solution.
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.
van Dijk-Wolthuis
W N
WN
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands.
van Steenbergen
M J
MJ
Underberg
W J
WJ
Hennink
W E
WE
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
D002021:Buffers; D003911:Dextrans; D008689:Methacrylates; D012996:Solutions; D014867:Water