An Evaluation of Amoxicillin/Clavulanate Stability in Aqueous Systems, Including Its Suitability for Outpatient Parenteral Antimicrobial Therapy (OPAT).

Purpose: Amoxicillin/clavulanate antibiotic combination is suitable for treating a range of infections, including some suited for Outpatient Parenteral Antimicrobial Therapy (OPAT). The aim of the study was to evaluate shelf-life values of amoxicillin at clinical concentrations in the presence of clavulanate for use in OPAT.

Methods: A stability-indicating HPLC assay was developed and validated. Kinetic studies were performed at 1 mg/mL and 15 mg/mL amoxicillin at 40-60 °C. Studies in elastomeric infusers included the pH lowered from 8.73 to 6.52 for 1 mg/mL; 8.85 to 7.69 for 7.5 mg/mL and 8.68 to 8.40 for 15 mg/mL amoxicillin plus clavulanate and stored at 2.9 °C.

Results: Amoxicillin and clavulanate eluted at 5.2 and 3.0 minutes, respectively, with linear concentration relationships. Forced degradation retained base-line separation of each component in the presence of degradation products. Amoxicillin 1 mg/mL had a shelf-life of 4.85 hours at pH 6.53 and 40 °C which on extrapolation to 25 °C was 22.8 h. Clavulanate was 1.38 h at 40 °C and 4.0 h at 25 °C. Amoxicillin 15 mg/mL at pH 8.34 gave a shelf-life of 0.11 h at 40 °C and clavulanate 0.41 h. In elastomeric infusers, amoxicillin 1 mg/mL, with lowering pH from 8.73 to 6.52, improved the shelf-life at 2.9 °C from 72 to >263.8 h and similarly for clavulanate. At 7.5 mg/mL amoxicillin, lowering pH from 8.85 to 7.69 improved the shelf-life from 4.2 to 51.8 h and clavulanate from 4.2 to 48.0 h. At 15 mg/mL amoxicillin, the shelf-life values at pH 8.68 or 8.40 were 3.8 h and 1.6 h and similarly for clavulanate.

Conclusion: Amoxicillin and clavulanate showed adequate stability at 2.9 °C for OPAT storage at 1 mg/mL and possibly 7.5 mg/mL, but not 15 mg/mL. Low shelf-life values at 25 °C also limit administration times.