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

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.

The role of concentration on drop formation and breakup of collagen, fibrinogen, and thrombin solutions during inkjet bioprinting

The influence of protein concentration on drop formation and breakup of aqueous solutions of fibrous proteins collagen, fibrinogen, and globular protein thrombin in different concentration regimes is investigated during drop-on-demand (DOD) inkjet bioprinting. The capillary-driven thinning and breakup of dilute (c/c* < 1, where c is the concentration and c* is the overlap concentration) collagen, fibrinogen, and thrombin solutions is predominantly resisted by inertial force on the initial onset of necking. The minimum diameter (Dfmin(t)) of the necked fluid up to the critical pinch-off time (tc) scales with time as Dfmin(t) ∼ (tc − t)2/3, a characteristic of potential flows. Although the capillary-driven thinning and breakup of semidilute unentangled collagen (1 ≤ c/c* ≤ 4) and fibrinogen (1 ≤ c/c* ≤ 1.3) solutions is predominantly resisted by inertial force on the initial onset of necking, the breakup of droplets is delayed beyond tc, where the minimum diameter of the necked fluid decreases exponentially with time because of the resistance of elastic force. The resistance of viscous force to the necking of both the dilute and semidilute untangled protein solutions is negligible. Aggregates or subvisible particles (between 1 and 100 μm) constantly disrupt the formation of droplets for the semidilute unentangled protein solutions, even when their inverse Ohnesorge number (Z) is within the printability range of 4 ≤ Z ≤ 14. Although aggregates are present in the dilute protein solutions, they do not disrupt the formation of droplets.