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Focus on Force Profile and Stroke-To-Fire for pMDI

Innovating for patients is at the core of Nemera’s mission; over 50 engineers and experts work to achieve this at the Innovation Center for Devices (ICD) at La Verpillière near Lyon in France. Part of the ICD’s responsibilities is the development of laboratory methods and equipment to better characterise product performance. The following discusses a new integrated method that combines stroke to fire (STF) testing with the analysis of force profiles (FPs) of a pressurised metered dose inhaler (pMDI) valve. It has been developed and implemented specifically for Inhalia®, Nemera’s new proprietary pMDI valve platform.

IN DETAIL

Understanding and setting the FPs of a valve is critical during development, with a minimum of two forces having to be measured and controlled:

• The actuation force, which is closely linked with the patient’s ability to deliver a dose
• The return force, which ensures the repositioning of the valve into rest position and a good refill ability of the dosing chamber

Nowadays, these are checked with a simple method applied directly on a single inhaler using a tension and compression machine. Apart from these two forces, the entire FP of a valve also needs to be evaluated and monitored to understand the mechanical behaviours, such as friction or blockage points, for a given design.

Dose counters, which are an increasingly common sight on pMDIs, add specific conditions to the valve. One of those is that the actuation has to be counted before the valve is fired; doing so will avoid doses that are dispensed but not counted. To enable this, the stroke of the dose counter itself has to be well defined on the one hand, and the valve suppliers need to be able to set and verify the STF of the valve on the other hand.

STF is defined as the stroke of the valve at the time when the fluid path between the dosing chamber and the environment opens. That is when the dosing chamber starts to empty and the pMDI dispenses the dose to the patient. It is the accurate synchronisation of the stroke to count and STF that will make the pMDI with dose counter safe for the patient.

In some cases, an additional requirement for the valve is to provide enough energy towards the end of the return stroke to re-set the counter. This further increases the need to control the return force of the valve.

LEVER METHOD

To accurately determine the STF of a valve and its variability is challenging, as it is the result of many factors such as component materials, dimensions, lubrication, crimping accuracy, user actuation, speed profile and many more. Therefore, no ‘off the shelf’ solution is proposed by lab equipment suppliers for experimental characterisation of this attribute. To date, the industry has adopted several methods to determine the STF – for example, acoustic exploration, optic/laser or other visual characterisation tracking the forming spray – but none of them provide a simultaneous, integrated measurement of FP and STF. For this reason, the ICD team has decided to develop a proprietary in-house method and suitable equipment to determine the STF with the objective of simplicity, repeatability, accuracy and robustness integrated into the existing FP testing.

This new method is specifically designed to reduce manual workload in the laboratory. The core of the method is to use the energy of the spray to move a detection mean: a lever (see Figure 1). The right hand side of the lever features a flat impaction surface for the spray exiting the valve stem, while the left hand side features a flag with a small hole. The lever is balanced at rest position, where an optical signal in form of a light beam passes through the hole. When the inhaler is actuated and the STF is reached, the spray impaction forces the lever to rotate so that the flap covers the light beam. This will produce a binary signal. The lever must be well balanced and as light as possible to minimise its inertia and the spray energy required to make it rotate. In addition, the alignment of the hole on the flap and the optical sensor has to be accurate to reduce rotation of the lever needed to switch the signal.

AN INTEGRATED SYSTEM

Nemera’s tension and compression machine is used to control the actuation and measure the FP of the pMDI valve. The new lever fixture is then connected and provides an input into this machine, so that the valve FP and STF can be recorded simultaneously (see Figure 2).

The method developed is illustrated by means of an example test with an Inhalia® prototyped valve. The output data is plotted in Figure 3, page 16.

The STF is determined when the optical signal changes. This happens at around 2.6mm on this given valve. The advantage is that the associated force evaluated at STF, shown in Figure 3 as 27.9N, can be observed at the same time.

CALIBRATING THE STF MEASUREMENT

A gap between the STF value given by this method and the effective STF (at the time the first particles are dispensed) is expected by design, and is due to two main factors:

• Sufficient energy from the spray is required to make the lever rotate
• Minimal rotation of the lever is required to make the signal change

A high speed camera (HSC) was used to record the test sequence at 500 frames to understand this gap (see Figure 4, page 16). Trials were done first with the detection lever to learn how it moves, and subsequently without it to observe the spray directly at the exit of the stem. The latter should provide the most accurate and shortest STF evaluation.

Through good alignment of the camera with the fixture, the post-treated video data allows extraction of the actuation speed profile (valve stroke versus time). In addition, it links the motion of the lever or the start of the spray with the valve stroke. The gap between the STF detected by HSC at the start of the spray and the STF given by the mechanical method described earlier is plotted in Figure 5.

As expected, the HSC evaluation shows lower values than the mechanical Nemera method by 0.15mm. Analysis of the posttreated video data, with or without the lever, enables evaluation of the influence of the two factors, described above, to the gap found. Each factor contributes about 50% to the total gap.

Knowing the size of the gap, the STF coming from the mechanical method can now be adjusted downwards so that the effective STF can be taken into account. Using the effective STF, the pMDI with dose counter is safe for the patient to use as it will not dispense any doses without counting.

Different actuation speeds, valve doses and material combinations could impact the valve STF. A wider study is underway to understand the impact of those variables and quantify the effective ‘true’ STF of different valve configurations.

FULLY IMPLEMENTED

The STF detection method and associated equipment have been developed as a dedicated tool to support the characterisation of pMDI valve performance and is now being used for all design verifications on the Inhalia® platform. The integrated evaluation of the valve FP and the STF will allow Nemera to support pMDI developments with dose counters and provide pMDIs that are compliant with the current regulatory requirements and safe for patients.

Acknowledgements
Nemera would like to thank Myriam Giraud, Pierre Pintus and Olivier Joly as authors of this article.

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