Stability of Ampicillin Sodium

Author: Kimberley Patterson

  • Thesis download: available for open access on 28 Nov 2019.

Patterson, Kimberley, 2018 Stability of Ampicillin Sodium, Flinders University, College of Science and Engineering

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Abstract

The Hospital in the Home (HITH) program has been designed to medically treat patients in their own homes. These treatments include but are not limited to intravenous (IV) infusions. For effective, long-term treatment, these infusions would be longer and at higher concentrations than those made in a clinical environment. Before drugs are used for the treatment of patients in the HITH program, research is required to determine if the drug is effective and safe as IV infusions in these conditions. Ampicillin sodium is a drug of the penicillin family, commonly used in oral and IV infusions. As this drug can fight against both Gram-negative and Gram-positive bacteria, it is of interest for the use in the program. However, ampicillin sodium has already been previously reported as unstable in aqueous solution. Therefore, for the higher concentrations in non-clinical environments, the stability of the drug needs to be investigated.

The degradation of ampicillin sodium (initial concentrations of 16 mg.mL-1 and 56 mg.mL-1) in water, saline solutions, and in citrate and phosphate buffers, was analysed at various temperatures, using UHPLC-UV detection and 1H NMR. The results revealed that initial concentration and temperature have a large influence on the stability of ampicillin sodium; the higher the concentration and temperature, the less stable the drug. In water solutions, it was determined that the drug, at 5 oC, for the low concentration (16 mg.mL-1), had a degradation rate of 3.59 ± 1 seconds-1 in which it may be administered over a long period of time. The higher concentration (56 mg.mL-1) at the same temperature, degraded faster (19.6 ± 1 seconds-1). It was determined that water was the most viable solution for the stability of the drug to be used in the HITH program.

A proposed degradation mechanism of ampicillin sodium was produced from the identification of the degradation products, using LCMS. These degradation products included multiple stereoisomers of ampicilloic acid, ampicillin dimer and ampicillin diketopiperazine Some degradation products displayed a dependence on both temperature and concentration, some were independent to the initial concentration of ampicillin sodium, and others were independent to temperature. The IV fluid used showed that they could influence the degradation pathways for some products.

Keywords: Pharmacokinetics, Stability, Kinetics, Ampicillin

Subject: Chemistry thesis

Thesis type: Doctor of Philosophy
Completed: 2018
School: College of Science and Engineering
Supervisor: Ingo Koeper