Investigation of The Surface Properties of Plasma Treated Pressurised Metered Dose Inhaler Canisters and Their Influence on Formulation Performance

Pressurised metered dose inhalers (pMDIs) are drug delivery devices used in the treatment of various lung diseases and conditions such as asthma and COPD. A typical device consists of a canister, a metering valve, and an actuator. Within the canister is the pressurised propellant and drug which exists in either a solution (dissolved in propellant) or suspension (solid particles dispersed in propellant). pMDIs generate an inhalable aerosol through the depression of the metering valve, causing an opening to form between the metering chamber (containing a mixture of pharmaceutical ingredients and the propellant) and the atmosphere. The difference in pressure between the chamber and the atmosphere causes rapid ejection and evaporation of the mixture, thus forming an aerosolised plume that is then inhaled by the patient to deliver treatment to the lungs. Several factors can affect this process and result in changes in dose consistency and the stability of the formulation within the canister. These include humidity, changes in the propellant (CFCs to HFAs), and drug/propellant's prolonged contact with the inhaler components, e.g., the canister aluminium surface and metering valve.

One area of investigation relates to treatments of the internal surface of the aluminium canisters that contain the pharmaceutical ingredients, reduce the risk of aluminium-catalysed drug degradation or drug loss due to adhesion to the canister surface. Many surface coating techniques exist; however, this project will focus on the most recent, which employs plasma coating to deposit a fluorocarbon polymer (FCP) on the internal surfaces of canisters. This has a lower environmental impact and may give better inhaler performance compared to other coating techniques. However, there is no published research into i) the characteristics and uniformity of plasma treated cannister surfaces, especially with different plasma coating parameters; ii) how the treatment affects the adhesion of drug particles to the cannister surface; iii) the effects of plasma treatment on drug delivery and stability. A better understanding of these issues would enable the plasma process to be optimised for different drugs and formulations .

This project will investigate these three areas of uncertainty using a range of experimental techniques. Surface characteristics and uniformity will be investigated with a range of microscopic techniques (incl. SEM, AFM, 3D) and investigations of surface chemistry (incl. XPS and contact angle measurement). AFM will also be used to quantify the adhesion of a variety of drugs to different canister surfaces. Findings from all these studies will be triangulated with the findings of drug delivery and stability studies, to determine the relationship between plasma coating parameters, surface characteristics and inhaler performance.

Aerosol science has a significant impact on a broad range of disciplines, extending from inhaled drug delivery, to combustion science and its health impacts, aerosol assisted routes to materials, climate change, and the delivery of agricultural and consumer products. Estimates of the global aerosol market size suggest it will reach $84 billion/year by 2024 with products in the personal care, household, automotive, food, paints and medical sectors. Air pollution leads to an estimated 30-40,000 premature deaths each year in the UK, and aerosols transmit human and animal infections. More than 12 million people in the UK live with lung disease such as asthma, and the NHS spends ~£5 billion/year on respiratory therapies. Many of the technological, societal and health challenges central to these areas rely on core skills and knowledge of aerosol science. Despite this, an Industrial Workshop and online survey (held in preparation for this bid) highlighted the current doctoral skills gap in aerosol science in the UK. Participating industries reported that only 15% of their employees working with aerosol science at doctoral-level having received any formal training. A CDT in aerosol science, CAS, will fill this skills gap, impacting on all areas of science where core training in aerosol science is crucial.

Impact on the UK aerosol community: Aerosol scientists work across governmental policy, industrial research and innovation, and in academia. Despite the considerable overlap in training needs for researchers working in these diverse sectors, current doctoral training in aerosol science is fragmentary and ad hoc (e.g. the annual Fundamentals of Aerosol Science course delivered by the Aerosol Society). In addition, training occurs within the context of individual disciplines, reinforcing artificial subject boundaries. CAS will bring coherence to training in the core physical and engineering science of aerosols, catalysing new synergies in research, and providing a focal point for training a multidisciplinary community of researchers. Working with the Aerosol Society, we will establish a legacy by providing training resources for future researchers through an online training portal.

Impact on industry and public-sector partners: 45 organisations have indicated they will act as CAS partners with interests in respiratory therapies, public health, materials manufacturing, consumer and agricultural products, instrumentation, emissions and environment. Establishing CAS will deliver researchers with the necessary skills to ensure the UK establishes and sustains a scientific and technical lead in their sectors. Further, it will provide an ideal mechanism for delivering Continuing Professional Development for the existing workforce practitioners. The activity of CAS is aligned to the Industrial Strategy Challenge Fund (e.g. through developing new healthcare technologies and new materials) and the EPSRC Prosperity Outcomes of a productive, healthy (e.g. novel treatments for respiratory disease) and resilient (e.g. adaptations to climate change, air quality) nation, with both the skilled researchers and their science naturally translating to long-lasting impact. Additionally, rigorous training in responsible innovation and ethical standards will lead to aerosol researchers able to contribute to developing: regulatory standards for medicines; policy on air quality and climate geoengineering; and regulations on manufactured nano-materials.

Public engagement: CAS will provide a focal point for engaging the public on topics in aerosol science that affect our daily lives (consumer products, materials) through to our health (inhalation therapeutics, disease transmission and impacts of pollution) and the future of our planet (geoengineering). Supported by a rigorous doctoral level training in aerosol science, this next generation of researchers will be ideally positioned to lead debates on all of these societal and technological challenges.