Degradation kinetics of methacrylated dextrans in aqueous solution

J Pharm Sci. 1997 Apr;86(4):413-7. doi: 10.1021/js9604220.

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.

MeSH terms

  • Buffers
  • Chromatography, High Pressure Liquid
  • Dextrans / chemistry*
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Kinetics
  • Methacrylates / chemistry*
  • Solutions / chemistry
  • Temperature
  • Water / chemistry

Substances

  • Buffers
  • Dextrans
  • Methacrylates
  • Solutions
  • Water