Effect of Reconstitution Solvents and Containers on Kinetics and Safety of Cephradine Neutralised with L-Arginine

Kinetic of Degradation of Cephradine

Abstract

The effect of reconstitution solvents such as water, 0.5% metronidazole solution, 0.9% sodium chloride and 5% dextrose injections, have been investigated on the kinetics of degradation of cephradine
neutralised with L-arginine contained in glass, polyvinylchloride (PVC) and polyethylene pthalate (PET) containers at 5, 15 and 30 ^oC. The analytical method described in USP-31 for the analysis of cephradine
injection was employed in this study and validation in respect of specificity, linearity, accuracy and precision was observed. The degradation of the compound showed first-order kinetics and the degradation rate constants k_obs were found in the range of 1.84-3.07 ´ 10^-3/h (r² = 0.990-0.999) at 5 ^oC, 2.3-4.2 ´ 10^-3/h (r² = 0.993-0.999) at 15 ^oC and 7.18-9.97 ´ 10^-3/h (r² = 0.998-0.999) at 30 ^oC, respectively. Cephradine
showed maximum stability in dextrose solution followed by water, sodium chloride and metronidazole injections, however, linear effect of containers on degradation rate could not be established. The  extended degradation did not change the kinetics of the reaction. The abnormal toxicity/ safety test on mice for the admixtures in different containers at various temperatures showed no abnormal toxicity.