Lung diseases are a major global health burden. 300 million people live with asthma worldwide and it is predicted that chronic obstructive pulmonary disease will become the third-leading cause of death by 2020. The inhalation of therapeutic aerosols is a familiar medical strategy to treat lung diseases. Aerosol therapy can also achieve high antibiotic concentrations in the lung to treat infections. When aerosols are targeted into the deep lung, inhaled therapy also provides a means to achieve systemic concentrations of active pharmaceutical ingredients and avoid the need for injections of drugs that are destroyed in the gastrointestinal tract, such as insulin. Despite its potential, many patients fail to gain the full benefits of inhaled therapies in treating lung disease, and systemic drug delivery has failed to achieve the market break-through it deserves. Some of the ineffectiveness arises from the inability of patients to use their therapy correctly. However, achieving aerosol deposition in the lungs is a major challenge even for those patients with good inhaler technique. The challenge is to produce a portable dosage form containing components that can be redispersed by a patient. Redispersion must be achieved with uniformity of a dose in the form of an aerosol with the properties required for lung penetration. Turning potentially inhalable particles into formulated products that can be manufactured reproducibly, and that achieve consistent aerosolization performance between different patients poses many challenges that are poorly-solved. Consensus meetings of industrial, academic and regulatory experts in the field of inhaled medicine have identified the need to improve control and consistency of drug deposition performance. Additionally there is a need to improve our understanding of how and why the characteristics of starting materials interact with the manufacturing conditions to lead to inter-batch and inter-patient variability in aerosol characteristics. At the heart of the challenge is the fact that the very property of the particles that makes them suitable for inhalation (their small size which, at less than 5 microns, is less than the diameter of a human hair) also causes them to clump together as agglomerates. Theme 1 of the project will employ synthonic engineering (a computer modelling technique based on the molecular structures of pharmaceutical ingredients) to achieve new abilities to predict agglomeration behaviour early in development, and the interactions of agglomerate materials with inactive ingredients in the formulation. Theme 2 will use new measurement techniques that image how agglomerates interact with each other in powders to develop an understanding and characterize how the agglomerate phase in a formulation leads to inter-patient or inter-batch variability of product performance. Theme 3 will underpin the knowledge gained from powder imaging to assess the underlying causes of agglomeration. Better, integrated experimental measurement techniques will be developed to characterize the material properties that regulate the extent and strength of interactions between particles. Theme 4 focuses on developing new computational models to characterize the behaviour of agglomerated powders during the mechanical processes occurring when a patient breathes through an inhaler, and when powders are processed during manufacturing. The final component of the project is to integrate the knowledge gained in Themes 1-4 to engineer quality into a range of test products selected by an advisory panel. This will be achieved by using the prediction and measurement techniques to inform formulation scientists, device designers and process engineers of the steps that are appropriate to mitigate the effects of agglomeration on product performance. The ultimate goal is to use the techniques developed to translate the therapeutic benefits for patients using inhaled medicines from molecules to manufactured products.

An aerosol consists of solid particles or liquid droplets dispersed in a gas phase with sizes spanning from clusters of molecules (nanometres) to rain droplets (millimetres). Aerosol science is a term used to describe our understanding of the collective underlying physical science governing the properties and transformation of aerosols in a broad range of contexts, extending from drug delivery to the lungs to disease transmission, combustion and energy generation, materials processing, environmental science, and the delivery of agricultural and consumer products. Despite the commonality in the physical science core to all of these sectors, doctoral training in aerosol science has been focussed in specific contexts such as inhalation, the environment and materials. Representatives from these diverse sectors have reported that over 90% of their organisations experience difficulty in recruiting to research and technical roles requiring core expertise in aerosol science. Many of these will act as CDT partners and have co-created this bid. We will establish a CDT in Aerosol Science that, for the first time on a global stage, will provide foundational and comprehensive training for doctoral scientists in the core physical science. Not only will this bring coherence to training in aerosol science in the UK, but it will catalyse new collaborations between researchers in different disciplines. Inverting the existing training paradigm will ensure that practitioners of the future have the technical agility and confidence to move between different application contexts, leading to exciting and innovative approaches to address the technological, societal and health challenges in aerosol science. We will assemble a multidisciplinary team of supervisors from the Universities of Bristol, Bath, Cambridge, Hertfordshire, Imperial, Leeds and Manchester, with expertise spanning chemistry, physics, biological sciences, chemical and mechanical engineering, life and medical sciences, pharmacy and pharmacology, and earth and environmental sciences. Such breadth is crucial to provide the broad perspective on aerosol science central to developing researchers able to address the challenges that fall at the boundaries between these disciplines. We will engage with partners from across the industrial, governmental and public sectors, and with the Aerosol Society of the UK and Ireland, to deliver a legacy of training packages and an online training portal for future practitioners. With partners, we have defined the key research competencies in aerosol science necessary for their employees. Partners will provide support through skills-training placements, co-sponsored studentships, and contribution to taught elements. 5 cohorts of 16 doctoral students will follow a period of intensive training in the core concepts of aerosol science with training placements in complementary application areas and with partners. In subsequent years we will continue to build the activity of the cohort through summer schools, workshops and conferences hosted by the Aerosol Society, virtual training and enhanced training activities, and student-led initiatives. The students will acquire a perspective of aerosol science that stretches beyond the artificial boundaries of traditional disciplines, seeing the commonalities in core physical science. A cohort-based approach will provide a national focal point for training, acting as a catalyst to assemble a multi-disciplinary team with the breadth of research activity to provide opportunities for students to undertake research in complementary areas of aerosol science, and a mechanism for delivering the broad academic ingredients necessary for core training in aerosol science. A network of highly-skilled doctoral practitioners in aerosol science will result, capable of addressing the biggest problems and ethical dilemmas of our age, such as healthy ageing, sustainable and safe consumer products, and climate geoengineering.