DYNAMIC EVENTS IN AUTOINJECTOR DEVICES
2.1 Actuation Sequence of a Typical Spring-Actuated Autoinjector
Figure 2.1 is a simplified schematic of the internal components and actuation se- quence of a typical spring-actuated autoinjector device. Note that only the key components relevant to the present discussion are represented for simplicity.
Only panel A of Figure 2.1 is considered at this time, where the device is in its initial state just before actuation. The device bottom features are in contact with the patient’s skin. The key component is the syringe mounted inside the autoinjector.
It is frequently referred to as apre-filled syringe(PFS) due to the fact that it is often pre-filled with the medicament in the factory, prior to being mounted inside the autoinjector, and prior to being sold to a patient. The syringe can be fabricated with
Figure 2.1: Simplified schematic of the actuation sequence of a typical spring- actuated autoinjector device.
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(a) BD HyPak – pre-filled syringe with a pre-attached needle.
(b) BD HyLok – pre-filled syringe without a pre-attached needle.
Figure 2.2: Examples of pre-filled, glass syringes from BD. Reproduced from http://drugdeliverysystems.bd.com.
plastic, but most autoinjector devices currently available on the market make use of glass syringes. A review paper bySacha, Rogers, and Miller (2015)provides more information on pre-filled syringes.
A needle, as shown inFigure 2.1, is attached to the syringe. The root of the needle is located at the bottom end or tip of the syringe. The needle can be pre-attached to the syringe in the factory, as shown inFigure 2.2a. In other cases the user needs to attach the needle to the syringe prior to using the autoinjector device, as shown in Figure 2.2b(Sacha, Rogers, and Miller, 2015).
The top end of the syringe typically has a flange. The internal and external geometry of the syringe can vary largely from one model to the other, especially in the vicinity of the tip. In some syringes the transition from the barrel to the needle is achieved with a smooth converging section, as depicted in Figure 2.1. In other cases the syringe ends with a flat wall which has a narrow channel at the center for the liquid to enter the needle, similar to the schematic shown inFigure 1.2. In all cases the tip of the syringe is sealed during storage. Adequate sealing is necessary to prevent the ingress of contaminants toward the inside of the syringe.
The syringe is sealed at its other end using a plunger-stopper. This is depicted in Figures2.1 and2.2. The plunger-stopper is typically fabricated with an elastomer, and it serves two important purposes (Sacha, Rogers, and Miller, 2015):
1. it seals the syringe content during storage to avoid drug contamination;
2. it serves as a piston used to pressurize the syringe and extrude the medicament into the patient.
Figure 2.3: Schematic of a pre-filled syringe in a vertical, tip-down configuration with (left) and without (right) an air gap.
It is common for the syringe to not only contain the liquid drug solution, but to also contain an air gap or headspace (Sacha, Rogers, and Miller, 2015). This is shown in Figures2.1and2.3for the case of a syringe in a vertical, tip-down configuration.
The presence of an air gap typically results from the syringe filling method. In some cases the presence of an air gap is a necessity, as is the case for drug solutions which contain suspensions. The air gap has important consequences on the transient events during device actuation. This is discussed further in the remainder of this thesis.
There are different means of supporting the syringe within the device. One approach is to support the syringe using its flange. Another approach is to support the syringe using the shoulder located in the vicinity of the tip. Sometimes a combination of both is used. In the configuration shown in Figure 2.1, the shoulder is used to decelerate the syringe, and the flange is used to accelerate the syringe by the means of a needle insertion mechanism.
The power pack is only partially shown inFigure 2.1. The power pack is responsible for actuation of the device. It consists primarily of an actuation button (not shown),
13 a spring (not shown), and a driving rod. The spring is often contained within the driving rod, and the spring force is applied directly on the tip of the driving rod which, in turn, applies a force on the plunger-stopper of the syringe. The needle insertion mechanism is initially attached to the driving rod.
The actuation sequence shown inFigure 2.1is now discussed using panels A through D. In panel A the device is in its initial state, just before actuation: the unshielded needle is attached to the syringe tip, the device bottom features are in contact with the patient’s skin, and the pre-filled syringe is mounted inside the device and sealed by a plunger-stopper.
In panel B the device has been activated, and the spring-actuated driving rod is moving forward. The insertion mechanism attached to the driving rod is in contact with the flange of the syringe, and this accelerates the syringe assembly forward.
The forward motion of the syringe inserts the needle into the patient. The syringe is decelerated to a complete stop once the needle has reached the adequate depth for injection. The deceleration of the syringe results from the contact of the syringe shoulder on a device bottom feature which is part of the enclosing shell (not shown).
In panel C the driving rod is moving independently from the insertion mechanism, and it impacts on the plunger-stopper. The impact velocity and the force exerted by the spring-actuated driving rod on the plunger-stopper pressurizes the syringe, and this forces the medicament to be extruded through the needle and into the patient, as shown in panel D.