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Aiding respiratory drug delivery: pMDI valve considerations

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Andrew Lee, senior consultant at lab services and consultancy specialist, Broughton,  reports that packaging selection is an important consideration for many drug products, particularly pressurised metered dose inhalers (pMDIs). In particular, pMDI valve design can be an important factor, as these components are crucial to the correct drug delivery.

Key insights:

pMDIs are a common treatment option for the 5.4 million people with asthma and the further 1.2 million who have COPD in the UK. The devices utilise pressurised canisters of propellant, with the drug in solution or suspension, to deliver small, metered doses into a patient’s lungs. This delivery can occur either directly, or via add-on devices like spacers and valved holding chambers (VHCs).

Best practice for pMDI design

Metering valves are key components in pMDIs, responsible for ensuring a consistent amount of formulation (and ideally drug) is delivered. In Stephen Stein et al.’s paper, they were described as “the heart of the system,” with “greater complexity than any other hardware subsystem”.  For the product to perform optimally, the valve must be matched to the product, accounting for factors such as formulation viscosity and desired particle size distribution.

Valve design variations can vary according to the exact formulation and dose required. Take an active pharmaceutical ingredient (API) suspended in the propellant, for example. Such a formulation would require a gathering ring as part of the metering valve to disperse the suspension and ensure uniform filling of the suspended API into the valve. However, the need for a gathering ring is completely negated if the drug substance is a solution.

Most pharmaceutical businesses will not manufacture their own valves. Instead, they will often partner with a reliable third-party manufacturer, and select from their available options. At the design stage, this will include making decisions on a suitable material and marrying up the metering chamber size (which is directly correlated to the dosage size) with the formulation. Based on the available valve configurations, the pharmaceutical manufacturer may need to adjust their formulation chemistry to suit the valve design. They will also need to conduct their extractables and leachables studies to ensure the selected material has no impact on patient safety.

What are the risks?

As well as being a crucial component for consistent drug delivery, concerns about pMDI valves can lead to a mass product recall. In 2017, GlaxoSmithKline voluntarily recalled some 590,000 inhalers from the US market due to concerns that a packaging defect had occurred. The defect could cause propellant to leak via the valve and/or closure of the canister whilst the drug product was stored on pharmacy shelves.

Similarly, large recalls of mini spacers — often used by children and the elderly, in conjunction with pMDIs to coordinate inhalation — have occurred when manufacturing defects have caused incomplete fill via the entry orifice. This meant that patients might have received insufficient API amid a potential asthma attack.

Historically, such defects were a real issue, however, as the plastics industry has become more aligned with good manufacturing practice (GMP), such recalls have become rarer.

pMDI valves are crucial, helping millions of respiratory disease patients receive the correct dosage of API. To ensure safe and effective pMDI design, pharmaceutical manufacturers can partner with a science and regulatory consultancy that can advise on their design choices, perform extractables and leachables studies, and support with regulatory approval.

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