SUBCUTANEOUS INJECTIONS - A New Dimension for an Enhanced Injection Experience

INTRODUCTION

The global healthcare landscape is undergoing a significant transformation, driven by demographic shifts and evolving patient needs. As populations grow and age, the prevalence of chronic conditions is rising, necessitating long-term therapeutic strategies, usually administered through subcutaneous injections. However, the increasing demand for less-frequent dosing and patient-cen­tric delivery methods is pushing the boundaries of current drug formulation and delivery systems.

To meet these expectations, pharmaceutical developers are exploring formulations that allow for reduced injection volumes or extended dosing intervals. These innovations, while beneficial for patient adherence and quality of life, often result in high-vis­cosity solutions that present significant challenges in terms of dose delivery. High viscosity solutions (eg, those above 30 cP) can com­promise the ease and comfort of administration for patients with specific conditions, potentially impacting patient experience and treatment outcomes.

The following explores the impact of these market trends, fo­cusing on the technical and clinical challenges associated with delivering large-volume, high-viscosity subcutaneous injections. It also highlights the need for optimized delivery systems that can accommodate these formulations without compromising usability or efficacy, as well as the potential advantages such systems may offer for non-viscous injections.

MINIMIZING PATIENT PAIN DURING VISCOUS DRUG INJECTION

Theory of Needle Impact on Injection Forces
Injecting high-viscosity drugs using standard syringes can often lead to increased discomfort or pain for patients. The use of an 8-mm needle has been shown to help reduce this pain. In this section, we will explore how needle length can influence in­jection comfort, particularly in the context of high-viscosity formu­lations. Multiple forces are exerted during the injection process. One of them is the hydrodynamic force.¹ The following equation de­termines the hydrodynamic force required for fluid injection:

The force required to inject a fluid is directly proportional to the needle length (lNeedle) and inversely proportional to the fourth power of the needle radius (rNeedle). By reducing the exposed nee­dle length to 8 mm and using a 27G Special Thin-Wall needle with an enlarged internal diameter, the design minimizes the hy­drodynamic resistance. This results in lower injection forces, which not only improves the ease of administration, but also reduces the mechanical stress and discomfort experienced by the patient, thereby lowering the perception of pain.

Human factors studies conducted by Stevanato Group con­firmed a clear preference for
the 8mm STW needle, especially among both experienced and inexperienced self-injecting pa­tients.² The strong positive feedback was driven not only by the reduced injection force, but also by the psychological benefit of the shorter needle, which helped reduce anxiety and made the injection experience feel more manageable.

Why do RNS Internal Cavities Need to be Adjusted According to the Length of the Needle?
The Rigid Needle Shield’s (RNS) key functionality is to ensure the Container Closure Integrity (CCI), which is critical for preserving drug sterility, integrity, and pa­tient safety. Two areas enabling it to main­tain the CCI are represented in red in Figure 1A:

• Area 1: the cavity in contact with the tip of the syringe
• Area 2: the needle embedded in the rubber

The rubber component forms a tight, flexible seal around the needle and the sy­ringe tip, blocking any potential pathways that could lead to microbial ingress or product degradation.

RNS are designed to help the needle insertion in the center of the cavity. Follow­ing needle insertion into the rubber core (Figure 1B), the seal remains effective, thereby ensuring the product’s sterility and safety up to the point of administration. Therefore, with a lower needle length to support viscous product, having an RNS with adapted internal cavities is required to ensure an efficient seal.

Integration Within the Auto-Injector System
Ensuring component compatibility with auto-injectors is essential to facilitate at-home medication and self-administra­tion.

In this context, Alba^® and Nexa^® pre­fillable syringes have been specifically de­veloped to enable reliable integration into auto-injector platforms. Both syringes fea­ture tightly controlled dimensional toler­ances and optimized barrel geometries to ensure consistent fit, secure assembly, and reproducible delivery performance within the device. Critical dimensional parame­ters, including the overall syringe length without closure (L1), the length above the shoulder (L2), and the total length includ­ing the rigid needle shield (L3) (Figure 2), have been precisely defined to support ac­curate injection depth, while also facilitat­ing proper engagement during auto-injec­tor assembly.

In addition, the axial alignment be­tween the rigid needle shield and the sy­ringe barrel is carefully controlled during manufacturing to ensure repeatable per­formance and compatibility across auto­mated device assembly processes.

The 8mm RNS developed by Aptar Pharma integrates critical design and ma­terial to ensure optimal patented shell geometry, and the 4900GS rubber formu­lation enables a controlled Pull-Out Force (POF) while eliminating the risk of coring during needle insertion. This market-proven rubber formulation has been de­signed to ensure optimal compatibility with Biotech drug products.

To facilitate optimized integration with auto-injector systems, Aptar Pharma de­veloped an innovative proprietary design that allows for efficient removal by grip­ping the top (enabled by a mushroom-shaped profile) or via a molded edge at the base (Figure 1,C&D). This dual-access approach enhances compatibility with var­ious cap-removal mechanisms. Impor­tantly, the RNS maintains the same folding shell process as Aptar Pharma’s market-leading designs, which is instrumental in minimizing the risk of de-shielding.

Assessing the POF, which refers to the forces needed to remove the RNS from sy­ringes, as well as the deshielding forces (DF) (meaning the forces required to sep­arate the shell from the needle shield) is important. As auto-injector usage in­creases in the market, the variability and required POF values for compatibility with auto-injector mechanisms tend to be lower than those for stand-alone Pre-Filled Sy­ringes (PFS). The two forces measured shouldn’t overlap to ensure product’s proper function.

As highlighted in Figure 3, with a safe margin area, POF and DF of the P235Q don’t overlap.

How to Implement 8mm RNS & Syringe Without Impacting Machinability
Processability on the customer filling line is a key parameter to be considered in any development. Therefore, the rubber needle shield for the 8mm needle is com­bined with Aptar Pharma’s 0.5inch rigid shell for the auto-injector, and the syringe difference is only on the needle, meaning no external dimension variation, ensuring no modification of the customer’s filling line is required.

As a distinguishing feature in the fill­ing line, the NS design incorporates a spe­cific reduction in diameter at the top of the needle shield, visible through the shell win­dow (Figure 1,E). This feature provides a visible poka-yoke at every production stage, whether during RNS assembly, sy­ringe assembly, or filling, ensuring that sy­ringes with 0.5inch needles (E1) can be easily distinguished from those with 8mm needles (E2). As a result, the risk of mix-ups on filling lines is effectively prevented.

PERFORMANCE ENHANCEMENT THROUGH THE PLUNGER & SYRINGE SYSTEM

Designing for Comfort: A Systemic View on Injection Force Management
The Role of Plunger-Barrel Interface: The plunger and syringe’s main functions are to preserve container closure integrity (CCI), maintain drug stability, and facilitate drug delivery to the patient.

The efficacy of CCI and precise dose administration is contingent upon an opti­mal interference fit between the plunger and barrel, facilitating adequate compres­sion and sealing. This interface induces friction during injection, dictated by pa­rameters such as applied force, friction co-efficient, rubber-glass interfacial adhesion, viscoelastic hysteresis of the elastomer, ef­fective contact area, surface roughness, and the extent of lubrication or siliconiza­tion.

The break-loose (BL) force, required to initiate plunger movement, and gliding forces (GF), needed to sustain movement, are crucial for successful injections. They determine the ease-of-use of a PFS and its integration into an auto-injector.

Stevanato Group’s Alba^® Syringe, Fea­turing a Proprietary Cross-Linked Coat­ing: To enable proper movement within the system, both the glass barrel and the rubber stopper typically require lubrica­tion with silicone oil. In the Alba^® plat­form, a proprietary cross-linked silicone coating is applied to the inner barrel sur­face, creating a stabilized, low-migration lubricant layer. This immobilized coating is designed to maintain drug stability over time (even in the presence of ag­gressive surfactants often used in highly concentrated biologics), while ensuring consistently low and predictable glide forces. Such performance is particularly critical in auto-injector applications, where reliable break-loose and glide forces are essential to ensure that even low-force springs can successfully deliver the full dose to the patient.

Aptar Pharma’s PremiumCoat®
For decades, Aptar Pharma offers a large range of plungers designed to be compat­ible with syringe and devices and using ul­trapure formulations. To address the most sensitive drugs, Aptar Pharma launched in 2021 PremiumCoat plungers platform, combining an ETFE film coating, which is applied at the drug contact surface, with our single, pure formulation 6720 and its state-of-the-art innovative manufacturing process. The following introduces how Pre­miumCoat combined with Nexa® and Alba® syringes can address the challenges of injecting large viscous drugs.

As previously detailed, current trends aim at reducing dosing frequency for pa­tients and increasing the viscosity of the solutions delivered.

Performance Testing With Viscous Drugs
Using a dynamometer, technical experts assessed the BLGF of Premium­Coat®1-3mL plungers in combination with Alba^® and Nexa^® syringes filled with water-like fluid and fluids of various vis­cosities. Each measurement yields a graph of forces, which indicates the BL and aver­age GF (Figure 4, A-D). First, the speed was fixed at 300 mm/min, and the solu­tion had various viscosities (1 – 30 – 50 Cps), comparing the results of a Nexa^® sy­ringe when it has a 0.5inch 27G TW and 8mm 27 Special Thin Wall needle pushed by an Aptar PremiumCoat 1-3mL plunger.

Second, the test was conducted with an Alba^® and Nexa^® syringe filled with water (1Cp) solution at various speeds to assess the speed impact in AI. Comparing BLGF in a system of Nexa^® syringe and Aptar Pharma’s PremiumCoat^® 1-3mL plungers with an 8mm STW or ½” TW needle, there is little difference for non-vis­cous liquids. However, with viscous drugs (30 or 50 Cps), both forces decrease by 25% when using the 8mm STW needle.

The speed of injection can vary and is a critical parameter in auto-injector per­formance. The faster an injection is done, the higher the speed will be. When using the Alba^® syringe (featuring a cross-linked silicone coating) in combination with the PremiumCoat^® 1-3mL, the system demonstrates improved consistency and reduced variability, particularly at higher injection speed. These results are driven by the combination of a stabilized, immobi­lized silicone layer on the syringe barrel and the proprietary 3-rib design of the PremiumCoat plunger. The 3 ribs maintain continuous contact with the barrel, ensur­ing constant pressure distribution with glass and therefore enabling smooth forces during the injection phase (Figure 5C).

How do the Functional Properties of PremiumCoat Facilitate Integration in Filling Lines?

Plungers were tested with both vac­uum and vent-tube stoppering machines, which are known for altering ETFE films in other coated plungers. In both methods, Aptar Pharma’s film-coated plunger demonstrated a great machinability com­patibility by maintaining its film integrity. For more details, read our article pub­lished on October 21 in Drug Develop­ment & Delivery titled Exploring How the Functional Properties of the PremiumCoat 1-3-mL Plunger Facilitate its Implementa­tion on Filling Lines & Enable the Delivery of Sensitive Vaccines & Biotech Drugs^.3

SUMMARY

In summary, driving innovation in in­jection systems demands a collaborative and patient-centric approach that unites pharmaceutical developers, device manufacturers, and technol­ogy partners. By keeping the patient at the center of each deci­sion, we can achieve solutions that not only optimize system performance, but genuinely enhance patient experience and safety. Aptar Pharma’s advanced Rigid Needle Shield, Premium­Coat^® Plunger, and its integration expertise (strengthened by a fruitful collaboration with Stevanato Group) stand as a testament to our commitment in supporting the evolving needs of the biotech industry. By leveraging our proven know-how and cut­ting-edge products, we support our partners to navigate the com­plex landscape of high-viscosity and novel drug formulations, accelerating and derisking drug development, while ultimately improving outcomes and quality of life for patients.

REFERENCES

1. Fischer, I., et al. (2015). Calculation of injection forces for highly concentrated protein solutions. International Journal of Pharmaceutics, 493, 70–74. doi:10.1016/j.ijpharm.2015.07.054.
2. On Drug Delivery Edition 5th October 2024 – A New Di­mension: Balancing Biologic Limitations & Patient Percep­tions for an Enhanced Injection Experience.
3. Cordier S, Guillemot L-H, Chardonnet A. SYRINGE PLUNGER – Exploring How the Functional Properties of the PremiumCoat® 1-3-mL Plunger Facilitate its Implementation on Filling Lines & Enable the Delivery of Sensitive Vaccines & Biotech Drugs. Drug Dev & Del. October 2021: https://drug-dev.com/syringe-plunger-exploring-how-the-functional-properties-of-the-premiumcoat-1-3-ml-plunger-facilitate-its-implementation-on-filling-lines-enable-the-delivery-of-sensitive-vaccines-biotech-d/.

Enrico Barichello is Product Manager for the Syringe Platform at Stevanato Group. He earned a Master’s degree in Industrial Engineering from the University of Padua. Since joining Stevanato Group in 2017, he has worked closely with cross-functional teams to define and execute the roadmap for new products, including the Alba® platform. Since 2023, he has overseen the glass syringe platform, and as of January 2025, also manages the polymer syringe platform, driving innovation and growth across Stevanato Group’s syringe portfolio.

 

Crystal Salvans is the Product Line Manager for PFS at Aptar Pharma’s Injectables division. She earned an Engineering degree in Packaging from ESIREIMS and began her career as a Packaging Engineer at Johnson & Johnson (now Kenvue), before joining Aptar Pharma Injectables in 2015. With expertise in injectables packaging, she has held roles in Technical Support, Project Management, and Sterile Gamma Irradiation, managing a Technical Product Management team. Currently, she leads a team managing the project and product life cycles for plungers, RNS, and tip cap components.