Effect of b-cyclodextrin derivatives on the kinetics of degradation of cefotaxime sodium in solution state

The influence of b-cyclodextrin (b-CD) and its derivatives (diethyl-b-CD, hydroxyl propyl-b-CD and maltosyl-b-CD) on the stability of cefotaxime was investigated in aqueous buffer solutions of pH 3.5 and pH 7.5 at 25 and 37oC. The degradation rates were determined by a stabilityindicating reversed-phase high-performance liquid chromatographic method. It was found that the degradation of cefotaxime sodium followed first-order reaction kinetics with respect to its concentration. The degradation rate increased upon increasing temperature from 25 to 37oC in both pHs and in either absence or presence of CDs. All the studied CDs except DM b-CD accelerated the degradation rate of cefotaxime sodium in the solution of pH 3.5 at 25oC to different extents while at 37oC and in buffer solution of pH 7.5 all CDs accelerated the degradation with a higher rate than in pH 3.5. This may be due to the fastest mechanism of de-esterification at the C-3 position at alkaline pH 7.5 than at acidic pH 3.5. There are two mechanisms of degradation of cefotaxime sodium which are de-esterification (hydrolysis of 3-acetoxy group) and b-lactam cleavage (lactonization). The acceleration effect on the degradation was higher with parent b-CD than with its derivatives which may be due to the nature of the complex formed. 1H-NMR confirmed the complex formation between cefotaxime sodium and either b-CD or DM b-CD in aqueous solution.