Stability of midazolam and noradrenaline stored in cyclic olefin copolymer AT-Closed Vials® and polypropylene syringes during 365 days
5 October 2016F. Feutry1,3, S. Genay1,2, C. Velghe1, C. Barthélémy1, B. Décaudin1,2, P. Odou1,2 1 Univ. Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables
et les Technologies Associées, F-59000 Lille, France
2 Pharmacy institute, University Hospital, Lille, France
3Oscar Lambret Centre, Lille, France
Midazolam (MDZ) and noradrenaline (NA) are drugs commonly used in intensive care units to control sedation and hemodynamic status of patients. They required a dilution step by the nurse several times a day. To decrease preparation risks, they could be compounded by the pharmacy, provided that stability is sufficient.
50mL cyclic olefin copolymer AT-Closed Vials® (Aseptic Technologies) and polypropylene syringes (Plastipak®, Becton Dickinson) were filled with MDZ or NA (Mylan) diluted in saline at respectively 1mg/mL and 0.2mg/mL. Study was performed according to the SFPC/GERPAC guidelines during 365 days at 2 temperature conditions: -20°C, 5°C. Concentrations were determined by an HPLC/UV stability indicating method, expressed as mean±standard deviation and considered stable if the concentration stayed over 90% of the initial concentration value. Particulate contamination, pH evolution and sterility were followed.
Solutions were stable during 365 days in AT-Closed Vial® at -20°C (MDZ 99.01±0.90%, NA 98.91±0.54%) and 5°C (MDZ 97.98±0.96%, NA 99.52±0.36%) and in syringes at -20°C (MDZ 99.29±0.85%, NA 98.92±0.98%) and 5°C (MDZ 97.89±0.51%, NA 99.42±0.51%). There was no modification of pH. Sterility and particle tests were in accordance with European Pharmacopeia after 365 days whatever the storage conditions.
MDZ and NA are stable during 365 days at 5°C and -20°C. Storage at 5°C should be preferred to exclude freezing-thawing issues. AT-Closed Vial® could be chosen for their automated aseptic filling process and for logistic considerations particularly taking into account the space gains.