DYNAMIC EVENTS IN AUTOINJECTOR DEVICES
2.3 SureClick Autoinjector
41 whereδ is the air gap size, as indicated in Figure 2.3. The air gap compression is discussed further inChapter 4, where a model which can be used to estimate the peak pressure and the rise time of the pressure pulse is introduced.
In summary, if the force F applied on the plunger-stopper increases slowly to the final value, this results in a slow and gradual increase of the liquid pressure to a value Pqs =F/Ab,i. This is the idealized pressurization profile as there are no excursions of the pressure abovePqs. On the other hand, when the forceFis applied impulsively on the plunger-stopper the peak pressure in the liquid can exceedPqs, and this creates stresses and strains in the syringe’s walls. As discussed inChapter 3, peak magnitudes as large as 4 to 10 times the value of Pqs have been measured in a SureClick autoinjector. The pressure waves created in the liquid are very sharp when there is a direct contact between the plunger-stopper and the liquid. Adding and increasing the size of the air gap reduces the sharpness of the pressure waves created in the liquid (the sharpness of the pressure waves is further discussed in Chapters3to5).
To end this section, it is important to recognize that all three transient events are of very short duration (i.e., a few milliseconds at most). The transient events are followed by the extrusion phase, which is relatively long (i.e., a few seconds). The liquid pressure during the extrusion phase is equal toPqs. Equation 1.1can be used successfully to estimate the syringeability of a drug solution, but it can’t be used to predict the peak pressure in the liquid or the peak wall stresses in the syringe.
Although Equation 1.1 can be used to scale some parameters of the autoinjector device in a quasi-static sense, it does not say anything about the potential for device failure related to the dynamic events.
Figure 2.20: SureClick autoinjector device used by Amgen. Reproduced from Amgen (2016).
The external user actions required to operate a SureClick autoinjector are briefly reviewed. The various steps are described in the user manual distributed with the device (Amgen, 2016), and the sequence can be summarized as follows:
1. Remove the SureClick autoinjector from the package.
2. Inspect the SureClick autoinjector.
3. Prepare and clean the injection site. A proper injection site can be a thigh, the abdomen, or the outer area of an upper arm.
4. Pull the needle shield off (i.e., the white cap) when you are ready to inject.
5. Stretch or pinch the injection site to create a firm surface.
6. Place the end of the autoinjector on the skin at a right angle, and firmly push down the autoinjector onto the skin. This unlocks the internal mechanism.
7. When ready to inject, press the actuation button (a "click" is heard).
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Figure 2.21: Schematic of the key features of a SureClick autoinjector device.
8. The injection is complete when a second "click" is heard, up to 15 seconds after actuation.
9. Remove the autoinjector and dispose.
The transient events (events 1, 2, and 3) occur between steps 7 and 8 of the user sequence.
Figure 2.21 is a simplified schematic of the internal components of a SureClick autoinjector. In a SureClick device, the pre-filled syringe is mounted inside a syringe carrier. The syringe carrier is fabricated with plastic, and its primary role is to support the syringe within the device. The syringe carrier also ensures proper alignment of the syringe within the device. The contact point between the syringe and the syringe carrier is located at the shoulder level. Note that a needle is pre- attached to the syringe before the device is distributed to patients.
The power pack is responsible for actuation of the device. A coiled spring is located inside the driving rod. The spring is pre-compressed before the device is distributed to patients, eliminating the need to "prime" the device before use.
The stiffness of the spring in the SureClick autoinjector considered herein is approx- imately 500 N/m. Note that there exist different versions of SureClick with different spring stiffness. The pre-filled syringe has the following approximate dimensions:
6 mm in inner diameter, 8 mm in outer diameter, and 64 mm in length (more precise values are provided inChapter 3). The diameter of the shell of the autoinjector is approximately 18 mm, and the length of the device is approximately 150 mm.
When the user activates the device by depressing the actuation button located at the top of the power pack, the internal mechanism of the power pack (not shown) releases the spring-actuated driving rod. The driving rod is then accelerated and impacts on the plunger-stopper, setting the syringe, the carrier and the liquid contained inside the syringe into motion (event 1). The impact of the driving-rod on the plunger-stopper
also initiates the pressurization of the syringe (event 3). Due to the friction between the plunger-stopper and the syringe, events 1 and 3 are not entirely decoupled from one another. In fact, no needle insertion mechanism is shown inFigure 2.21. Even if one is physically present in a SureClick, results indicate it does not play a significant role in the actuation sequence. As explained in Chapter 3, the acceleration of the syringe results from the friction between the plunger-stopper and the syringe, and from the pressure increase at the bottom of the syringe.
A few milliseconds after actuation the syringe carrier reaches its travel limit, and both the liquid and the syringe stop moving (event 2). Injection of the drug into the patient then follows over approximately 5-15 seconds.
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