Citation: Delcroix I, Dugand P, “Adjusting & Controlling Injection Speed by Design: Impact on Pain Perception”. ONdrugDelivery Magazine, Issue 75 (May 2017), pp 50-53.

Isabell Delcroix and Pascal Dugand describe a study of the multi-award-winning Safelia® auto-injector platform which showed how varying and slowing injection speed could reduce pain perception.

Figure 1: 1 mL and 2.25 mL versions of the Safelia® auto-injector.

Nemera’s generation of two-step autoinjectors, Safelia® (Figure 1), has been designed to ease the patient self-injection experience and to deliver a variety of drug products in glass syringes. These range from more fluid formulations to the most challenging drugs such as viscous, sustained-released, concentrated formulations, products for subcutaneous and intramuscular injection, and including larger volumes.

The Safelia® auto-injector:

  • Administers a large range of formulations and injection volumes; the platform can adapt by design to handle both fluid and highly viscous formulations, taking care specifically of biologics, sustained-released formulations and sheer-sensitive molecules, of up to 2.25 mL injection volumes
  • Improves the patient experience, with the possibility to reduce needle gauge, reduce injection time, and slow down the needle penetration inside the body tissues, and gives the possibility of a delayed retraction for viscous injections especially.


Subcutaneous injection is a common route for self-administration using syringes, prefilled syringes and auto-injectors. Subcutaneous injections are typically 1 mL. However, increasingly treatments tend to require up to 2 mL injections.

Factors leading to a perception of pain are well known:

  • Injection site choice
  • Needle gauge (large diameter needles)
  • Formulation active ingredients, temperature, viscosity, pH
  • Dose volume
  • Injection speed

It is observed that larger dose volume (2 mL versus 1 mL) and faster injection could lead to higher stress in the tissues at the site of injection, and consequently higher pain perception. It is usually considered that a practical injection time should not exceed 10 seconds, which leads to 0.2 mL/sec injection flow rates in the case of 2 mL injected volumes. As a result, compared with 1 mL syringes, it can be anticipated that the increased injection speed, could cause a higher perception of pain to patients.

Design features and benefits of the Safelia® device are summarised in Table 1.

Expected benefits

Standard Auto-Injector


Safelia Features

Creating possibilities for viscous injections with the same AI platform as for standard glass syringesInjects fluid and viscous drugs u to 1000 cP
Risk of syringe breakage eliminated
Possibility of using all (or no) syringe flanges
No stress on syringes flanges
Enables increased spring force and use of small gauge needles (less patient pain) without risk of glass breakageNo stress on syringe flanges
Reduction of pain at needle insertionAdjust needle insertion speed
Reduction of pain during injectionNo initial injection peak
Drug is delivered at the right depthNeedle insertion disconnected from injection

Table 1: Summary of design features and benefits of the Safelia® platform.


Nemera has conducted a study investigating how adjusting and controlling injection speed could impact on pain perception, in particular for viscous and large-volume injections.

The primary objective of this study was to estimate injection force increase in porcine adipose tissue in the case of high viscous formulations (100 cP) and large dose volume (2 mL). The final aim was to propose a way to optimise injection devices to minimise the perception of pain by patients.


In a first step, injection forces were performed at different speeds in air and in tissues. In a second step, the impact of injected dose on injection force was measured. Syringes of 2.25 mL, with 25G, ½” long needles were prefilled with a 100 cP Newtonian liquid. Injection force in tissue was measured consecutively for injection in air and in tissue:

1. Injection in air was performed to determine injection force without tissue back force.

2. Injection in porcine adipose tissues was then performed (injection depth 6 mm, simulating subcutaneous injection).

Tests were performed at three different speeds (90 mm/min, 135 mm/min and 180 mm/min).

The sequence is shown in Figure 2.

Figure 2: Injection sequences for injection force measurements.


The Injection force in porcine adipose tissue increases with injection speed. Injections at a flow-rate of 0.09 mL/s generated a maximum back force of 20 N. (Note that it was also confirmed that injecting at a 0.09 mL/s flow-rate after injections at 0.18 mL/s generated a maximum back force of 20N, i.e. 60 N minus 40 N.)

Injection forces in air and injection forces in porcine adipose tissue (Figure 3) can be considered to estimate the injection pressure in the tissue. By subtracting the injection force in air to injection force in tissue, the tissue back force can be evaluated (Figure 4).

As anticipated, a higher injection speed is associated to a higher tissue back force. It has been also observed that the injection force smoothly increases with increasing dose volume, leads to a back force increase of 8 N (see Figure 5). It has been also observed that injection forces in porcine adipose tissue presents large variations. (Note that injection at 0.18 mL/s flow-rate generated a maximum back force of 32 N.)

Figure 3: Relation between injection force and injection speed in porcine adipose tissue.

Figure 4: Injection forces measurements in air and in porcine adipose tissue.

Figure 5: Relation between injection force measurements and dose volume in porcine adipose tissue.


Injection force increase in porcine adipose tissue in the case of highly viscous formulations (100cP) at high speed and large dose volume (2 mL) have been observed. These measurements allowed a skin back force estimation. This information is very useful for auto-injector development.

Figure 6: Injection time prediction in air and in porcine adipose tissue.

For Safelia® auto-injector, we have developed a mathematical model allowing injection time prediction including back force. This model enables us to anticipate auto-injector design at an early stage. Considering our example, with a 100 cP Newtonian liquid, 2.25 mL syringe with 25G needle and a 100 N spring force, the injection time in porcine adipose tissue is 10 seconds greater than injection in air (see Figure 6).

Increasing auto-injector energy could allow the dose to be delivered within the expected delivery time; but different studies have shown that the higher injection speed and dose volume limit dose absorption by the tissues and induce greater pain.

There are generally two critical times in the injection cycle: start of injection and end of injection. At start of injection, injection speed is at its maximum (maximum energy). Diminishing the initial injection speed will lower the injection force and could lower pain perception.

At end of injection, dose volume is at its maximum, whilst tissues are saturated. Diminishing end of injection speed will lower injection force, favouring drug absorption. The resulting pressure drop in the tissues could help also to reduce pain perception.

By design, the injection speed profile of Safelia® can be tailored to minimise injection forces. This injection force control should prevent the initial injection peak force, and allow a better drug absorption, and could lead to less pain perception.

New generation auto-injectors have to deliver highly viscous formulation, in larger volumes.

Injection should be painless, and comfortable for users. Controlling injection speed is a way to achieve less painful injections.

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