Physicochemical stability of human insulin 1 I.U./mL infusion solution in 50 mL polypropylene syringes

Abstract Objectives The objective of this study was to investigate the physicochemical stability of human insulin 1 I.U./mL injection solutions (Insuman® Rapid) diluted with 0.9% NaCl solution in 50 mL disposable three-piece polypropylene syringes and stored refrigerated or at room temperature. Methods 1 I.U./mL test solutions were prepared with Insuman® Rapid and 0.9% sodium chloride infusion solution in 50 mL Original-Perfusor® syringes and BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or 48 h at 20–25 °C/diffuse room light in order to determine chemical stability. Additional test solutions were stored 28 days at 2–8 °C/dark followed by 24 h at 20–25 °C/diffuse room light to measure pH and particle counts. Human insulin concentrations were analysed by reversed-phase high-performance liquid chromatography at predefined time points. Test solutions were regularly inspected; subvisible particles and pH values were measured. Results Insuman® Rapid 1 I.U./mL injection solutions, stored at 2–8 °C/dark for 90 days showed a decrease of insulin content over time, regardless of the syringe type used. When kept at 20–25 °C/diffuse room light for 48 h, a slight decrease of the HI concentration was observed in both syringe types. No evidence of colour change, relevant particle formation or major pH-change was observed throughout the observation period in any test solution. Conclusions Insuman® Rapid 1 I.U./mL injection solutions can be prepared by dilution with 0.9% NaCl infusion solution in disposable 50 mL three-piece polypropylene syringes as suitable primary containers. Physicochemical stability has been demonstrated for at least 21 days stored at 2–8 °C/dark followed by 48 h at 20–25 °C/diffuse room light.