Drug delivery to the airways
The average human inhales approximately 12,000 L of air daily and each breath exposes the airways to a variety of agents of importance in health and disease.
Aerosols – a collection of particles and droplets suspended in air – are emerging as leading cause of disease.
The World Health Organization has reported that urban pollution including aerosols caused almost two million deaths from respiratory disease in 2009. Aerosols are also beneficial in treating disease.
Therapies have been inhaled by humans for thousands of years to treat lung diseases and the last 20 years have seen huge interest in systemic drug delivery via the lungs.
However, the majority of inhaled medicines are still used for the topical treatment of diseases of the airways such as asthma and chronic obstructive pulmonary disease (COPD).
The goal of our research in the Research Centre for Topical Drug Delivery and Toxicology is to advance the understanding of therapies for the treatment of lung disease.
What the group does
Despite the existence of successful pharmacological agents, the clinical effectiveness of inhaled therapies remains poor. The simple truth is that getting the drug to the target site of action in the lung remains as difficult today as it was when the first inhalation devices were developed.
The airways group focuses on characterising and mitigating the sources of variability in drug deposition in the lung as well as understanding the biopharmaceutics of inhaled aerosols following deposition.
Our research group focuses on developing new pharmaceutical technologies to produce aerosol particles, improve the science of aerosol formulation and understanding how patients can use their inhaled devices better.
The ongoing research activities of the airways group are:
- Clinical inhalation pharmaceutics
- Patient-dependence of drug delivery
- Development of in vitro respiratory tissue models
- Particle engineering and characterisation
- Development of bio-relevant formulation analysis
- Formulation of combination drug formulations
- Pulmonary absorption, distribution and metabolism (ADM)
Investigations to Improve Aerosol Deposition Profiles from Dry Powder Inhalers (DPIs)
This project began in March 2011 and develops the area of clinical inhalation pharmaceutics in the airways group. The project will investigate the typical inhalation profiles of patients and volunteers through DPI devices and the link of inhalation rate variations and disease control.
One key output has been the development of a cyclone device with reduced flow-rate dependence of aerosol delivery in collaboration with Dr Digby Symons at the Engineering Design Centre, University of Cambridge.
Engineering Multi-Component Delivery Systems for the Controlled Transcellular Transport of Inhalation Therapeutics
The delivery of two or more active pharmaceutical ingredients from inhalers is not a trivial issue. There is dispute as to whether pharmacological synergy exists for combinations such as fluticasone propionate and salmeterol xinafoate. The project seeks to understand the inter-particulate interactions governing the performance of combination DPI products.
Significantly we are investigating the effect of bulk and surface crystallinity of inhaled drug particles on their aggregation and aerosolisation behaviour. Darragh Murnane began this work while at King’s College London with funding from Pfizer Ltd. and the BBSRC.
The Physics of Fluid Flow and Atomisation in Metered Dose Inhalers (MDIs)
Pressurised metered dose inhalers are the most popular dosage form used by patients, but they are also the most difficult to use correctly. This work, a collaboration with Kalok C Lee (Department of Engineering, De Montfort University) and Paul G Royall (King’s College London) is developing an in silico model to characterise atomisation behaviour of MDI formulations and serve as a device and formulation screening tool.
The Application of Solid-Phase Microextraction and Microsampling
The airways group is excited about this project to develop new analytical techniques for the quantification of ultralow concentrations of active pharmaceutical ingredients. Assessing the pharmacokinetics of inhaled compounds is difficult due to the typically low solubility and low plasma concentrations of inhaled compounds.
This study is a collaboration between GlaxoSmithKline, TDDT and Ute Gerhard (Department of Pharmacy, University of Hertfordshire).
Find out more about research in drug delivery to the airways.
Email Professor Darragh Murnane.