Optimizing high-dose delivery

Delivering high-dose or high-concentration therapies via subcutaneous injection presents unique challenges, primarily due to increased viscosity. Biologics with high-viscosity formulations often exceed 15cP, presenting challenges for injectability. Studies on immune globulin formulations have shown that protein concentrations above 200 mg/mL frequently exceed 20 cP, while 300 mg/mL formulations can reach viscosities as high as 128 cP¹. These constraints highlight the need for optimized syringe and autoinjector designs to accommodate high-viscosity drugs while maintaining usability and performance.

Study overview: evaluating the YpsoMate 2.25 and BD NeopakTM Glass Prefillable Syringe platform

The study assessed how syringe-needle configurations — including variations in needle gauge, length, and wall thickness — affect injection time when paired with the YpsoMate 2.25 autoinjector. By testing multiple syringe-needle combinations across different viscosities (Table 1), the objective was to analyze their impact on injection performance and provide insights into how these factors influence injection time into air.

The study focused on two main aspects:

1. Injection time across different needle-syringe configurations, evaluating whether dose delivery remained within a practical timeframe for various viscosities.
2. The interaction between autoinjector drive mechanism and syringe design, particularly at higher viscosities where increased resistance may influence injection performance.

Four BD Neopak^TM Glass Prefillable Syringe platform needle configurations were tested with the YpsoMate 2.25 autoinjector: 29G extra-thin wall (ETW) 8 mm, 27G special-thin wall (STW) ½ inch (12.7 mm), 27G special-thin wall (STW) 8 mm and 27G ultra-thin wall (UTW) 8 mm. The YpsoMate 2.25 autoinjector configuration (injection force) was kept constant throughout the study.

Each configuration was evaluated across up to five viscosity levels, reflecting a wide range of high-dose biologic formulations (Table 1): 11 cP, 23 cP, 36 cP, 53 cP, 70 cP.

Each configuration was tested with the autoinjector 20 times per viscosity level, ensuring statistically robust findings. The study analyzed both mean injection time and variability (standard deviation and range) to assess injection consistency across configurations.

Mechanical interaction between autoinjector and syringe

The syringe-needle configuration and autoinjector drive mechanism together determine injection efficiency and consistency. The study confirmed that both shorter 8 mm needles and ultra-thin wall (UTW) designs improve injection times, with 8 mm length reducing flow resistance compared to longer ½ inch needles, while UTW designs with increased inner diameters further optimize fluid flow without increasing needle gauge.

A well-adjusted autoinjector is essential to maintain consistent plunger movement and reliable dose delivery across viscosities. The YpsoMate 2.25 autoinjector applies controlled force, adapting to different syringe configurations while ensuring steady injection performance.

The study demonstrated how needle parameters and autoinjector drive mechanism robustness together influence injection time. The next section provides a detailed breakdown of injection time, showing the impact of needle-wall thickness and needle length across different viscosities for a given autoinjector configuration.

Key findings and performance breakdown

The results confirmed that higher viscosity leads to longer injection times, with UTW needles and 8 mm lengths improving efficiency at higher viscosities by reducing flow resistance. Injection times ranged from 3.63 seconds at 11 cP (27G UTW 8 mm) to 37.45 seconds at 70 cP (27G STW ½ inch), demonstrating the impact of viscosity and needle selection on the injection time.

As viscosity increased, UTW designs consistently reduced injection time, while special-thin wall (STW) needles and longer needle configurations introduced greater flow resistance. However, the YpsoMate 2.25 maintained a steady and reliable injection performance across all configurations, demonstrating its ability to apply consistent force and ensure smooth plunger movement, regardless of syringe variations and viscosity levels (figure 4).

At 11 cP, all syringe-needle configurations achieved efficient injection times, though differences were already measurable. The 27G UTW 8 mm needle injected in 3.63 seconds, making it the fastest among all tested configurations at this viscosity. The 27G STW 8 fmm needle followed at 5.10 seconds (14% longer than UTW), while the 27G STW ½ inch needle took 6.08 seconds (40% longer than UTW) and the 29G ETW 8 mm took 8.13 seconds (124% longer than UTW). For a given needle gauge, both needle-wall thickness and length influence injection time, with wall thickness playing the dominant role across all viscosities. Indeed, the Hagen Poiseuille equation shows that needle inner diameter has more weight than the needle length in the overall flow resistance of the needle. However, even at lower viscosities, shorter needle length provided a measurable improvement in reducing injection time. All injection times measurements resulted in well-accepted range of injection times, regardless of the needle gauge.

At 23 cP, the viscosity increase amplified the differences in injection time between configurations. The 27G UTW 8 mm needle injected in 7.30 seconds, confirming that thinner walls / larger needle ID significantly reduce fluid resistance. The 27G STW 8 mm needle required 10.05 seconds (38% longer than UTW), while the 27G STW ½ inch needle took 12.57 seconds (72% longer than UTW) and the 29G ETW 8 mm took 16.63 seconds (128% longer than UTW), reinforcing that both wall thickness and needle length contribute to injection time reductions, even if all measured injections were within the preferred range.

At 36 cP, the efficiency of the UTW needle design became even more pronounced. The 27G UTW 8 mm needle injected in 10.10 seconds, maintaining superior performance as other configurations slowed significantly. The 27G STW 8 mm needle required 15.72 seconds (56% longer than UTW), while the 27G STW ½ inch needle extended to 18.61 seconds (84% longer than UTW). These results confirm that longer needles introduce greater flow resistance, but needle-wall thickness continues to have the most significant impact on reducing injection time. The 29G ETW 8 mm needle remained within the practical injection time range at 25.90 seconds. However, as viscosity increased, projected injection times exceeded the preferred range, leading to the decision not to evaluate this configuration at higher viscosities, reinforcing that needle gauge and bore size must be optimized for higher viscosities.

At 53 cP, injection time increased significantly across all configurations, with the 27G UTW 8 mm needle maintaining the shortest injection time at 15.57 seconds. The 27G STW 8 mm needle took 22.60 seconds (45% longer than UTW), while the 27G STW ½ inch needle required 28.29 seconds (82% longer than UTW). The gap between STW and UTW designs widened further, confirming that UTW optimization is essential for efficient injection of high-viscosity drug formulations like biologics.

At 70 cP, injection times ranged from 20.42 to 37.45 seconds, varying by up to 83% between configurations. The 27G UTW 8 mm needle completed injection in 20.42 seconds, while the 27G STW 8 mm needle remained within the practical range at 28.63 seconds. The 27G STW ½ inch needle took 37.45 seconds (83% longer than UTW), confirming that longer, thicker-walled needles become increasingly inefficient for high-viscosity therapies. These results demonstrate that both shorter needles and thinner walls contribute to faster injection times, particularly as viscosity increases.

As shown in Figure 4 and 5, the error bars represent the standard deviation across 20 measurements per condition, illustrating the variability in injection times for each needle configuration. The data confirm that higher viscosities led to longer injection times, with error bars increasing slightly at higher viscosities, reflecting greater flow resistance and its effect on injection consistency. However, the overall variability remained within an expected range, with standard deviations across all conditions staying below 0.45 seconds, reinforcing the consistent and repeatable performance of the YpsoMate 2.25 autoinjector combined with the 2.25mL BD Neopak™ Glass Prefillable Syringe platform. These findings highlight the importance of optimizing syringe selection and autoinjector drive mechanism to maintain predictable injection performance, even under varying viscosity conditions.

Through their partnership, Ypsomed and BD are advancing self-injection solutions by enabling integration of the YpsoMate autoinjector platform with the BD Neopak™ XtraFlow™ Glass Prefillable Syringe (Figure 6). This collaboration provides pharmaceutical and biotech companies with flexible options to select the optimal syringe configuration for their formulation needs, balancing injection time, and delivery consistency. By combining the expertise in syringe and needle technologies from BD with the leadership in autoinjector design from Ypsomed, the partnership ensures reliable and user-friendly self-injection systems, even for high-viscosity and complex formulations.

References and disclaimers

1. Yadav J, Uddin S, Civati F, et al. Developing ultra-high concentration formulations of human immune globulins for subcutaneous injectables. J Pharm Sci. 2025;114(3):1605-1614. doi:10.1016/j.xphs.2025.01.028.
2. Schneider, A., Mueller, P., Jordi, C., Richard, P., Sneeringer, P., Nayyar, R., … Lange, J. (2019). Hold the device against the skin: the impact of injection duration on user’s force for handheld autoinjectors. Expert Opinion on Drug Delivery, 17(2), 225–236. https://doi.org/10.1080/17425247.2020.1704730

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