title: Stability of micafungin sodium solutions at different concentrations in glass bottles and syringes.
abstract: Micafungin is a costly treatment and packaging of 50 mg or 100 mg bottles only are available, while doses lower than 5 mg and 20 mg are often necessary in neonates and paediatrics patients, respectively. The stability of micafungin sodium in polypropylene syringes and glass bottles was studied at different concentrations. Solutions of micafungin diluted with NaCl 0.9% were prepared in glass bottles (20 and 10 mg/mL) or syringes (1 and 0.5 mg/mL) and stored at 25 °C, 60% humidity (RH), in the dark (ICH conditions). Solutions were also exposed to heat (70 °C) or alkaline solution (NaOH) in order to force degradation. Samples were analysed at days 1, 5, 8 (for bottles) and also 15 (for syringes) after the preparation and assayed in triplicate. Stability was studied using a stability-indicating high-performance liquid chromatographic method. Syringes stored at 25 °C retained over 90% of their initial concentration over the study period. Temperature and alkaline conditions had significant effect on the stability of micafungin, leading to apparition of degradation products. Moreover, sub visible particles were in the specification of the European Pharmacopeia along 15 days. To conclude, micafungin diluted in NaCl 0.9% and stored in polypropylene syringes was chemically stable for at least 15 days at 25 °C in the dark.
authors.affiliation: University Hospital of Angers, Pharmacy Department, 4 rue Larrey, 49933 Cedex 9 Angers, France; L'Université Nantes Angers Le Mans, INSERM U1066, Micro et Nanomédecines Biomimétiques, IBS, 4 rue Larrey, 49933 Cedex 9 Angers, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Briot
authors.affiliation: University Hospital of Angers, Pharmacy Department, 4 rue Larrey, 49933 Cedex 9 Angers, France.
authors.forename: Sandy
authors.initials: S
authors.lastname: Vrignaud
authors.affiliation: University Hospital of Angers, Pharmacy Department, 4 rue Larrey, 49933 Cedex 9 Angers, France; L'Université Nantes Angers Le Mans, INSERM U1066, Micro et Nanomédecines Biomimétiques, IBS, 4 rue Larrey, 49933 Cedex 9 Angers, France. Electronic address: frederic.lagarce@univ-angers.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lagarce
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D054714:Echinocandins / Q000737:chemistry*; D005898:Glass / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D055666:Lipopeptides / Q000737:chemistry*; D000077551:Micafungin; D019999:Pharmaceutical Solutions / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D013594:Syringes
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D019999:Pharmaceutical Solutions; D011126:Polypropylenes; D012965:Sodium Chloride; D000077551:Micafungin
keywords: CIVAS; HPLC; Micafungin; Polypropylene syringe; Stability