Improving the stability of potassium clavulanate in admixture with amoxicillin

Co-amoxiclav is a fixed combination of the sodium salt of amoxicillin (amoxiNa) and the potassium salt of clavulanic acid (clavK). Although clavulanic acid has weak antibacterial activity when used alone, its combination with certain penicillins results in a synergistic effect which expands the spectrum of activity of the penicillin against many strains of beta-lactamase producing bacteria. Preformulation studies indicate that clavulanic acid undergoes acid-base catalysed reactions depending on pH and the presence of buffer salts. Maximal stability of clavulanic acid is reported to be at pH 6.3. Although amoxicillin is subject to similar degradation pathways it appears to be more stable than clavulanic acid. In fact, evaluation of the stability of this combination in intravenous form as well as in oral suspensions showed that amoxicillin was markedly more stable than clavulanic acid.Therefore, in this paper, the stability of the admixture is assessed, in terms of clavK stability only. The pH of the reconstituted intravenous mixture of amoxiNa and clavK is in the range 8.5–9.5.The low stability of clavK at this pH range can affect the efficacy and safety of therapy. Since visible degradation (apparent by a colour change) has been observed before its administration, it is considered of interest to improve the stability of the mixture.