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

Abstract

The effect of reconstitution solvents such as water for injection, 0.5% metronidazole injection, 0.9% sodium chloride injection and 5% dextrose injection, has been investigated on the kinetics of degradation of cephradine neutralized with L-arginine contained in glass, polyvinylchloride (PVC) and polyethylene pthalate (PET) containers at 5, 15 and 30°C. The analytical method described in USP-31 for the analysis of cephradine injection was employed in this study after slight modification and validation in respect of specificity, linearity, accuracy and precision. 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 hr-1 (r 2 =0.990-0.999) at 5°C, 2.3-4.2 x 10-3 hr-1 (r 2 =0.993-0.999) at 15°C and 1.18-9.97 × 10-3 hr-1 (r 2 =0.998-0.999) at 30°C, respectively. The compound showed maximum stability in dextrose solution followed by water for injection, sodium chloride injection and metronidazole injection; 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.