Transcript Drug Delivery Systems Spraymiser TM Valve

SpraymiserTM Valve: Designed with Patient Use in Mind
Lesley Williams, Victoria Velasco, Dan Heyworth & Lisa Bradley
3M Health Care Ltd, Up Brooks, Clitheroe, Lancashire, BB7 1NX, England
In this paper, the robustness of the SpraymiserTM
valve in terms of retention of prime over extended
periods of time and through life valve functionality is
investigated with patient use in mind.
Table 1, Results of an extended prime retention study using EPDM Spraymiser
valves tested with active and placebo formulations
Percentage Retained Prime
Formulation
Period of nonuse (days)
Placebo
Active
Placebo
Active
Active
Active
3 days
3 days
6 days
6 days
7 days
14 days
Valve up
Valve down
100%
99.3%
100%
99.6%
100%
100%
-
Valve
horizontal
-
100%
100%
99.9%
100%
A suspension formulation was packaged in pMDIs
fitted with a Spraymiser valve and tested through life
following two shake methods: Shake A – a fast
vertical shake, where no inversion of the unit takes
place; Shake B – a slow rolling shake during which
the unit is fully inverted. Figure 3 shows the shot
weight data for 40 consecutive shots from the middle
of life. The pMDIs displayed consistent shot weight
performance through life, with overall %RSD
(relative standard deviation) values of 2.2% with the
fast, vertical shake and 0.8% with the slow, rolling
shake.
Through Life Unit Consistency
When the valve is to be used in conjunction with a
dose counter it is important that the valves perform
consistently through unit life in terms of force
characteristics for force driven dose counters and
valve travel for displacement driven counters.
Figures 1 and 2 show the force to fire and valve
displacement respectively, for EPDM Spraymiser,
showing consistent performance throughout the unit
life with a suspension formulation.
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Force to Fire Unit (N)
Increasing demands on pressurised metered dose
inhaler (pMDI) hardware are associated with the
potential delivery of systemically active drugs (e.g.
insulin, morphine etc) and the need to deliver low
shot products for the delivery of controlled drugs or
long acting/ infrequently used treatments (1). A key
attribute for pMDIs intended for use with these low
dose or single shot products is the delivery of
reproducible shots without the need for frequent repriming, following storage of the device. In addition,
the FDA’s recommendation regarding the integration
of dose-counting mechanisms into pMDIs also
highlights the need to develop robust pMDIs that
deliver accurate and reproducible shots through life
that will correlate with the information displayed by
the dose counter when operated by the patient (2).
Furthermore, variables associated with the patientdevice interaction, including shake method should
also be addressed and minimized to ensure that the
pMDI has laboratory-generated data more closely
aligned with patient use. Numerous test methods and
procedures are used to evaluate pMDIs, with some of
these tests aimed specifically at valve performance,
including valve delivery, leakage, tail-off, and
priming studies (3).
valve down and valve horizontal for up to 2 weeks at
ambient conditions. Table 1 shows that the EPDM
Spraymiser valves retain prime for a full 2 weeks
when stored in these orientations across the range of
formulations tested.
[Error Bars denote +/- 1 SD]
Introduction
30
20
10
0
Start of unit life
Middle of unit life
End of unit life
Figure 3: Shot weight data for 40 consecutive shots per unit
from middle of unit life
Conclusions
Spraymiser valves can withstand periods of non-use
without the need for frequent re-prime. This has been
demonstrated with both active and placebo
formulations. The valves show consistent force to fire
and displacement through unit life. A simulation of
patient-device interaction using two distinct shake
regimes in shot weight studies through life
demonstrated the robustness of Spraymiser valves.
Figure 1: Through Life Force to Fire for Spraymiser Valves
References
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Prime Retention
Prime retention of both active suspension and
placebo pMDIs packaged with EPDM Spraymiser
valves was investigated. pMDIs were stored valve up
Enabling your success
Displacement (mm)
[Error Bars denote +/- 1 SD]
The addition of dose counters emphasises the need to
ensure that full shots are delivered by the unit
following periods of non-use. If, as a result of loss of
prime, the patient needs to take additional priming
shots through the life of the device, the impact on the
number of doses would be clearly displayed by the
dose counter leading to issues associated with failure
to deliver label claim.
2.5
1. Moore, J., Bradley, L., Charnock, P., and Brown,
S. (2004), “Container Closure System Solutions
for Delivering Low Numbers of Doses from a
Pressurised Metered Dose Inhaler,” Proceedings,
RDD IX, pages 333-336.
2
1.5
1
0.5
0
Start of unit life
Middle of unit life
End of unit life
Through Life Valve Delivery
2. US FDA Guidance for Industry (2003),
“Integration of dose-counting mechanisms into
MDI drug products.”
Under extreme shake regimes there is a potential for
formulation to be shaken out of the metering chamber
of valves, giving rise to variability in shot weight
through unit life.
3. Cummings, R. (1999) “pMDIs: CFC to HFA
transition – valve performance,” J Allergy &
Clinical Immunology, Vol. 104, Number 6, pages
S230-S235.
Figure 2: Through Life Displacement for Spraymiser Valves
3 Drug Delivery Systems