Inhalation drug delivery is mainly used for the treatment of lung conditions such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, bacterial infection as well as lung tumours through topical action on the lungs (Kleinstreuer, 2011). The fact that inhaled drugs can reach the blood system can be a drawback for lung therapy as it increases the risk of side effects. This is an issue for the delivery of certain inhaled active pharmaceutical ingredients (APIs) such as corticosteroids which increase the risk of osteoporosis in particular for postmenopausal women (Lipworth, 1999).
On the other hand, it can also present an advantage for inhalation therapy on the whole as it allows the delivery of different proteins targeting the systemic circulation, via the inhalation route. Chemotherapeutic drugs, nicotine, insulin and anti-migraine agents could be produced as inhalable compounds (Laube, 2005). This is the case for Afrezza, an inhaler for insulin delivery currently developed by MannKind.
The main advantage of the inhalation route compared to other delivery methods is its fast onset of action. It can be used to deliver APIs to the target sites much faster than the oral route which is the most common non-invasive delivery route. For example, short-acting bronchodilators such as albuterol start acting within minutes after inhalation. This advantage is of particular importance for the relief of asthma crisis where the rapidity of action of a drug can be vital. Conversely, orally administered bronchodilators must pass through the digestive system to reach the intestines where they can be absorbed into the bloodstream. As a result, the drug has its peak effect between 45 minutes and 90 minutes after absorption (Milner, 1981).
Treatment of lung diseases by inhalation also requires a lower amount of API than other delivery routes. Contrarily to orally absorbed drugs, inhaled drugs avoid the first pass metabolism in the liver which destroys small molecules. Big molecules such as proteins are also destroyed by acid and enzymes in the gastrointestinal tract. Systemically delivered drugs are distributed through the entire circulatory system whereas inhaled drugs are administered directly to the site of action in the lungs. As a result, much greater doses of API must be delivered orally in order to obtain the same therapeutic effect as inhaled drugs (Tiddens, 2004). Delivering low amounts of drugs can lower the costs of a therapy when delivering expensive APIs and can help reduce side effects.
There are two methods of inhalation which are nasal and oral inhalations. Oral inhalation is more efficient as a greater proportion of the aerosol can avoid filtration and reach the lungs (Agnew, 1984). For this reason, the industry and academic community focus particularly on the oral inhalation route. The three main types of inhalation devices using the oral inhalation route are the nebulisers, the dry powder inhalers (DPIs) and the pressurised metered dose inhalers (pMDIs).
For over half a century, pressurised metered dose inhalers (pMDIs) have been the most sold inhaler devices for the treatment of lung diseases. However, they suffer from significant drug deposition in the mouth and throat, mainly due to the aerosolisation of large and fast-moving droplets. This causes a high occurrence of side effects and is wasteful of drug. They are also affected by a low consistency of dosing and as a result users might not benefit from maximal device efficiencies.
Engineering and Pharmaceutical scientists have come together to study the effects of various design parameters of pMDIs on to their efficacy.
A one-dimensional computational model was developed to determine spray properties at the exit of the device where experimental measurements are difficult to conduct. The model simulated the discharge of pure HFA134a formulations and HFA134a-based suspension formulations containing fluticasone propionate; the latter representing a commercially available formulation.
Computational Fluid Dynamics models were then developed, and validated using Next Generation Impacter (NGI) and Particle Image Velocimetry (PIV) experiments. The combination of these computational and experimental methods allowed the investigation of the spray along its entire trajectory, providing a deeper insight on the spray properties from the device to the respiratory system.
ABOUT THE AUTHOR(S)
Ka Lok Lee
Dr Lee is currently a Principal Lecturer and the Programme Leader of the MEng/BEng Mechanical Engineering programme at the University of East London. He is a Senior Fellow of the Higher Education Academy and an Associate Member of IMechE. He served on the College Research Ethics Committee of King's College London, and was an elected member of the EPSRC College. His main research interests include flows in internal combustion engine manifolds, ports and cylinders; velocity and mixing characteristics of mixing vessels; flow characteristics of drug delivery devices and inhalation mechanics. Ka Lok Lee has published many refereed conference and journal papers.
Published: 2017-11-17
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