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

The influence of β-cyclodextrin (β-CD) and its derivatives (diethyl-β-CD, hydroxyl propyl-β-CD and maltosyl-β-CD) on the stability of cefotaxime was investigated in aqueous buffer solutions of pH 3.5 and pH 7.5 at 25 and 37°C. The degradation rates were determined by a stability-indicating 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 37°C in both pHs and in either absence or presence of CDs. All the studied CDs except DM β-CD accelerated the degradation rate of cefotaxime sodium in the solution of pH 3.5 at 25°C to different extents while at 37°C 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 β-lactam cleavage (lactonization). The acceleration effect on the degradation was higher with parent β-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 β-CD or DM β-CD in aqueous solution.