The Joint Pharmaceutical Analysis Group held a stability meeting in the Royal Society of Chemistry’s headquarters in London earlier this year. Attended by 65 delegates, its focus was on progress in stability testing and analysis. Here follows a summary of the presentations made at the meeting.The challenges of OPAT are discovering antimicrobial agents with appropriate characteristics for once- or twice-daily management, which are suitable to administer, safe and meet the requirements of the service in addition to the antimicrobial stewardship agenda. He contrasted the treatment of Staphylococcus aureus disease using either ceftriaxone or flucloxacillin, to demonstrate the challenges posed by once-daily dosing with ceftriaxone versus the narrow spectrum, favored representative, flucloxacillin, which required multiple daily dosing.
Administering antibiotics as continuous infusion via an elastomeric device is also a helpful alternative for Stability Testing, but there must be confidence that the drugs are steady within the 24-hour infusion period. There were no data meeting the NHS guidance on stability available for key antibiotics for OPAT, so the medication stability-testing programme was started to make data available for open access by the OPAT community.Dr Jamieson then Discussed the findings for flucloxacillin equilibrium in citrate buffer in two commercially available, ambulatory apparatus; Infusoria LV Baxter and Accuser Woo Young Medical. Initial stability evaluation revealed that the item was too shaky in WFI, 0.9 percent NaCl, MCP buffers, 5.25 percent citrate buffer pH ranges were pH 5-8; demonstrating both high degradation and precipitation.
Therefore, 0.3 percent citrate buffer was selected in two clinically‑relevant concentrations, which were stable for 24 hours when heated to 37°C. Additionally, stability in both elastomeric devices at two different concentrations was assessed. In both cases great stability data were created. A similar study was conducted with meropenem, but equilibrium for just six hours could be shown, limiting its usefulness in OPAT. Work was due to commence on ceftazidime, but important challenges with its stability and the formation of the neurotoxic degradant pyridine were recognised. Future projects include ceftazidime/avibactam and potentially benzyl penicillin, amoxicillin, cefepime and temocillin. The working party is eager to work in partnership with the pharmaceutical industry and device manufacturers to create and disseminate open access stability information.