Chemical stability of amoxicillin in non-electrically driven portable infusion pump ANAPA^®

Introduction
High doses of amoxicillin (100-300 mg/kg/j) are recommended in serious infections treatment (endocarditis, bone…). Beta-lactam’s PK-PD suggests continuous infusion use. Therefore, physico-chemical stability of amoxicillin is crucial to ensure safety and efficacy. Few data are available in the literature about amoxicillin stability but at a poor level of proof especially concerning analytical methods performed. In a previous work (JNI 2016) we have demonstrated that amoxicillin stability depends on concentration and temperature and we have determined optimized conditions for continuous infusion of high-dose amoxicillin. However, to our knowledge, those conditions require infusion device (20 ml/h, 240 ml) not yet available, at least in France. Recently, Asept InMed has commercialized a innovative portable pump (ANAPA^®) suitable for our conditions. ANAPA^® is a safe CO2 pressured infusion device containing a special relief valve for maintaining gas pressure and a glass capillary, allowing accurate flow rate. The aim of this work was to assess amoxicillin chemical stability in ANAPA^® and to investigate its infusion flow rate accuracy.

Materiel and methods
Infusion device (ANAPA^® 250ml/13h) were filled up using 12 vials of amoxicillin (Clamoxyl^® 500 mg) diluted with 120 ml of water for injection and 120 ml of sodium chloride 0,9%. Targeted concentration were 25 mg/ml.
Storage: tank and line tube were kept at room temperature (23.6 ± 0.6°C) ; filter and capillary tube were kept at 32°C (31.4 ± 2.0°C)
Concentration were determined using HPLC-UV: the method has been validated according to international guidelines (ICH). Infusion flow rate was measured by collecting and weighing the infused solution after one hour (density of the solution and evaporation have been taken into consideration).

Results
Average flow rate over 12 hours: 18.7 ml/h ± 1.5ml (density of the solution 1.055, evaporation : 0.243 ml/h ± 0.039 ml/h).
Initial concentration (n=3): 25.4mg/l ± 0.3mg/l. Residual concentration after 12 hours infusion (n=3): 92% ± 2%.

Conclusion
Amoxicillin (25 mg/ml) is stable for 12h in ANAPA^® device using easy and realistic storage conditions (device stored at room temperature and administration site near to the body temperature). Moreover, our results show that the infusion flow rate remains accurate all along the use of the ANAPA^®.

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