Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants

Autor: Rommert Wijnsma, Henderik W. Frijlink, Karin H M Larmené-Beld, Stefan van Berkel, Katja Taxis
Přispěvatelé: PharmacoTherapy, -Epidemiology and -Economics, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
antioxidant
Antioxidant
Drug Storage
Sodium
medicine.medical_treatment
Pharmaceutical Solutions/analysis
Pharmaceutical Science
chemistry.chemical_element
Sterilization/methods
Syringes/standards
Alkenes
Aquatic Science
030226 pharmacology & pharmacy
Antioxidants
norepinephrine
Injections
Norepinephrine (medication)
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Drug Stability
Norepinephrine/analysis
syringe
Drug Discovery
medicine
030212 general & internal medicine
Ecology
Evolution
Behavior and Systematics
Syringe
Olefin fiber
Drug Storage/methods
Chromatography
Antioxidants/analysis
Ecology
Syringes
Sterilization
General Medicine
Sodium metabisulfite
stability
Ascorbic acid
Pharmaceutical Solutions
Epinephrine
chemistry
Agronomy and Crop Science
Alkenes/analysis
Research Article
medicine.drug
Zdroj: Aaps pharmscitech, 21(7):247. SPRINGER
AAPS PharmSciTech
ISSN: 1530-9932
DOI: 10.1208/s12249-020-01784-z
Popis: Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, sodium edetate, sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.
Databáze: OpenAIRE
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