Longterm physicochemical stability of ready-to-administer human insulin injection solutions 1 I.U./mL in 50 mL plastic syringes

Abstract

Abstract Objectives The objective of this study was to investigate the physicochemical stability of ready-to-adminster human insulin (HI) 1 I.U./mL injection solutions of two different brand products diluted with 0.9% NaCl solution under different storage conditions either in 50 mL disposable plastic syringes or as bulk solution in infusion bags. Methods HI test solutions 1 I.U./mL were prepared with Huminsulin® Normal 100 and Actrapid® Penfill®, diluted with 0.9% sodium chloride infusion solution, and filled in Original-Perfusor® syringes or BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or at 20–25 °C/diffuse room light. Bulk solutions 1 I.U./mL prepared with Huminsulin® Normal 100 were stored in two different 3 L infusion bags (Ecobag® click and ExactaMix® EVA bag) at 2–8 °C/dark for five days. HI concentrations were determined by reversed-phase high-performance liquid chromatography at predefined time points. Beside regular visual inspection, subvisible particles and pH values were measured. Results Ready-to-adminster Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL prepared in 50 mL Original-Perfusor® syringes or BD® Perfusion syringes remained physicochemically stable for up to 90 days when stored at 2–8 °C/dark and for at least 14 days when kept at 20–25 °C/diffuse room light. Prefilled 3 L polyolefin infusion bags (Ecobag® click) are suitable for the preparation of Huminsulin® 1 I.U./mL bulk solutions. In ethylene vinyl acetate (EVA) bags, HI concentrations decreased rapidly. Conclusions Ready-to-administer Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL can be prepared in advance by dilution with 0.9% sodium chloride infusion solution and filled into 50 mL Original-Perfusor® syringes or BD® Perfusion syringes; subsequent storage at 2–8 °C/dark is possible for up to 90 days. For preparation of bulk solutions, the prefilled polyolefin infusion bag is appropriate.