The stability of amoxicillin trihydrate and potassium clavulanate combination in aqueous solutions
Abstract
The effect of various environmental factors on the stability of aqueous solutions of amoxicillin-clavulanic acid combination in a veterinary water-soluble powder product was investigated. In the swine industry, the combination is administered via the drinking water, where both substances are quickly decomposed depending on several environmental factors. The degradation rate of the substances was determined in solutions of different water hardness levels (German hardness of 2, 6 and 10) and pH values (3.0, 7.0 and 10.0), and in troughs made of different materials (metal or plastic). Increasing the water hardness decreased the stability of both substances, amoxicillin being more stable at each hardness value than clavulanate. Amoxicillin trihydrate proved to be most stable at an acidic pH, while increasing the pH decreased its stability (P < 0.05). Maximum stability of potassium clavulanate was experienced at neutral pH, while its decomposition rate was significantly higher at acidic and alkaline pH values (P < 0.01). The stability of the amoxicillin-clavulanic acid combination depends mainly on the less stable clavulanate, although the effect of metallic ions significantly increased the decomposition rate of amoxicillin, rendering it less stable in metal troughs than clavulanate (P < 0.05). Therefore, the amoxicillin-clavulanic acid combination should be administered to the animals in soft water, at neutral pH and in plastic troughs.
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The trends of CA decomposition in fermentation broth seem to deviate from first and pseudo-first-order kinetics previously reported for CA solutions prepared with standard reactant or commercial formulations.
“The trends of CA decomposition in fermentation broth seem to deviate from first and pseudo-first-order kinetics previously reported for CA solutions prepared with standard reactant or commercial formulations [10,19,23,25,26,27].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [26]
Clavulanic acid is more stable at a neutral pH.
“clavulanic acid was shown to be more stable at a neutral pH, as the decomposition rate was described to be higher at acidic or alkaline pH (Jerzsele and Nagy, 2009).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Jerzsele and Nagy, 2009
The decomposition rate of clavulanic acid is higher at acidic or alkaline pH.
“clavulanic acid was shown to be more stable at a neutral pH, as the decomposition rate was described to be higher at acidic or alkaline pH (Jerzsele and Nagy, 2009).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Jerzsele and Nagy, 2009
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Ser, H.-L., Law, J. W.-F., Chaiyakunapruk, N., Jacob, S. A., Palanisamy, U. D., Chan, K.-G., Goh, B.-H., & Lee, L.-H. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00522 · Cited by 90 · see citing works
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Gómez-Ríos, D., Ramírez-Malule, H., Neubauer, P., Junne, S., & Ríos-Estepa, R. (2019) · Antibiotics · doi:10.3390/antibiotics8010006 · Cited by 17 · see citing works
“The results obtained for the shelf-lives of CA in fermentation broth are comparable to the data obtained by Jerzsele and Nagy [26] for aqueous solutions of standard clavulanate, Bersanetti et al. [10], Ishida et al. [18] and Roubos et al. [20] for CA degradation in fermentation broths at room temperature.”
Result
- Authors
- Jerzsele, Á., & Nagy, G.
- Affiliations
- Magyar Agrár- és Élettudományi Egyetem (HU)
- ORCID
- Jerzsele, Ákos
- Venue
- Acta Veterinaria Hungarica
- Publisher
- Akademiai Kiado Zrt.
- Published
- 2009-12-01
- Volume
- 57
- Issue
- 4
- Pages
- 485-493
- ISSN
- 0236-6290 (ISSN-L)
- 1588-2705
- OpenAlex
- W2154696331
- Cited by
- 37
- References
- 0
- Citations by year
- 2026: 2 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 3
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Veterinaria Hungarica (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
- Keywords
- amoxicillin trihydrate, potassium clavulanate, drug stability, aqueous solutions, water hardness, pH effect, pigs, drinking water administration
- MeSH terms
- Anti-Bacterial Agents, Drug Stability, Drug Storage, Hydrogen-Ion Concentration, Solutions, Time Factors, Amoxicillin-Potassium Clavulanate Combination
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