1. Lesley Williams, Victoria Velasco, Dan Heyworth & Lisa Bradley 3M Health Care Ltd, Up Brooks, Clitheroe, Lancashire, BB7 1NX, England 3 Drug Delivery Systems Spraymiser TM Valve: Designed with Patient Use in Mind Enabling your success Introduction 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 re- priming, 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 patient- device 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). In this paper, the robustness of the Spraymiser TM valve in terms of retention of prime over extended periods of time and through life valve functionality is investigated with patient use in mind. 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. Prime retention of both active suspension and placebo pMDIs packaged with EPDM Spraymiser valves was investigated. pMDIs were stored valve up Prime Retention 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. Conclusions 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.US FDA Guidance for Industry (2003), “Integration of dose-counting mechanisms into MDI drug products.” 3.Cummings, R. (1999) “pMDIs: CFC to HFA transition – valve performance,” J Allergy & Clinical Immunology, Vol. 104, Number 6, pages S230-S235. References Through Life Valve Delivery 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. 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. 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. Figure 1: Through Life Force to Fire for Spraymiser Valves Figure 2: Through Life Displacement for Spraymiser Valves Through Life Unit Consistency 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. Figure 3: Shot weight data for 40 consecutive shots per unit from middle of unit life