Stability of intravenous flucloxacillin solutions used for hospital-in-the-home

Abstract

Background: Despite the uncertainty regarding flucloxacillin's stability, flucloxacillin solutions are routinely used as 24-hour ambulatory infusions for hospital-in-the-home patients. Aim: To determine the stability of flucloxacillin solutions in a simulated hospital-in-the-home environment and to assess whether flucloxacillin loss can be minimised via pH control. Method: Samples of flucloxacillin 5% and 12% solutions were prepared with either sodium chloride 0.9% or water for injection and with or without 5 mL phosphate buffer (0.384 M; pH 7). Flucloxacillin 5% solutions were tested in elastomeric infusion devices and the 12% solutions in polyvinyl chloride bags. All of the solutions were refrigerated for 6 days and then half of them were incubated at 37 °C for 24 hours. The remainder of the refrigerated solutions acted as controls. Incubated solutions were sampled for pH and high performance liquid chromatography analysis on Day 0, and Day 6 at 0, 12, 18 and 24 hours. Controls were sampled on Days 0, 6 and 14. Acceptable shelf life was ± 7.5% of initial flucloxacillin content. Results: Refrigerated buffered controls remained stable for 14 days while the unbuffered controls were stable for 6 days. All of the buffered solutions were stable at 37 °C after 24 hours, except for flucloxacillin 12% in water for injection. Incubated unbuffered flucloxacillin 5% in water for injection lost approximately 27% flucloxacillin and all of the other incubated unbuffered solutions lost up to 60%. Incubated unbuffered solutions displayed significant yellowing and cloudiness. The pH of all solutions fell by approximately 1 unit, except for refrigerated buffered controls (fell by 0.5 units). Conclusion: Unbuffered flucloxacillin 5% and 12% solutions lost up to 60% of flucloxacillin content when stored at 37 °C for 24 hours. Adjusting pH with phosphate buffer kept the incubated solutions stable for at least 24 hours (except flucloxacillin 12% in water for injection).