Stability of 1-unit/mL insulin aspart solution in cyclic olefin copolymer vials and polypropylene syringes

Abstract

Abstract Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This study evaluated the stability of diluted insulin aspart solutions (containing insulin aspart and preservatives) at their most commonly used concentration in intensive care units (1 unit/mL), in 2 container types: cyclic olefin copolymer (COC) vials and polypropylene (PP) syringes. Methods Insulin aspart solution (1 unit/mL, diluted in 0.9% sodium chloride injection) was stored for 365 days in COC vials with gray stoppers and PP syringes at refrigerated (5±3°C) and ambient temperatures (25°C ± 2°C at 60% ± 5% relative humidity and protected from light). Chemical testing was conducted monthly using a validated high-performance liquid chromatography method (quantification of insulin aspart, phenol, and metacresol). Physical stability was evaluated monthly via pH measurements, visible and subvisible particle counts, and osmolality measurements. Sterility testing was also performed to validate the sterile preparation process and the maintenance of sterility throughout the study. Results The limit of stability was set at 90% of the initial concentrations of insulin aspart, phenol, and metacresol. The physicochemical stability of 1-unit/mL insulin solutions stored refrigerated and protected from light, was unchanged in COC vials for the 365-day period and for 1 month in PP syringes. At ambient temperature, subvisible particulate contamination as well as the chemical stability of insulin and metacresol were acceptable for only 1 month’s storage in PP syringes, while insulin chemical stability was maintained for only 3 months’ storage in COC vials. Conclusion According to our results, it is not recommended to administer 1-unit/mL pharmacy-diluted insulin solutions after 3 months’ storage in COC vials at ambient temperature or after 1 month in PP syringes at ambient temperature. The findings support storage of 1-unit/mL insulin aspart solution in COC vials at refrigerated temperature as the best option over the long term. Sterility was maintained in every condition. Both sterility and physicochemical stability are essential to authorize the administration of a parenteral insulin solution.