Improving the effectiveness of inhaled medicines
New research offers hope to millions of people who suffer from respiratory illnesses.
The effectiveness of respiratory medicines, such as those delivered by an inhaler or nebuliser device, depends on an often-complex drug aerosol formulation. New research from Professor Glyn Taylor and his team at Cardiff University have changed our understanding of inhaled medicine dose deposition patterns in the lung, offering help to patients suffering from respiratory complaints.
Formulating inhaled medicines
The research team has contributed to methodological advances in pulmonary pharmaceutical scintigraphy. This is a form of imaging involving a radioactive tracer. In this instance, the radiotracer was used for the accurate quantitation of both inhaled drug dose to lung and regional pulmonary drug deposition patterns.
During the 1990s, these advances were explored by Professor Taylor and colleagues in animal models, including a definitive report of the relationship between the site of drug deposition in the lung and extent of drug absorption. This led to several clinical research trials in healthy volunteers and patients to optimise the performance of new inhalation formulations and devices.
The use of radiolabelled formulations in these studies demonstrated how the inhalational manoeuvre impacts upon the regional deposition pattern of drug within the lung following delivery from both pMDI and nebuliser inhalation devices.This led the team to conduct research into experimental inhaled medicines, with the focus on moving formulating pMDI medicines away from chlorofluorocarbon (CFC) to hydrofluoroalkane (HFA)-based propellants. A propellant is essential in pMDI formulations to generate the drug aerosol upon activation of the inhaler. The switch from 'ozone-depleting' CFC propellants to 'ozone-friendly' HFA propellants is a requirement of the Montreal Protocol.
The Montreal Protocol is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion.
In 2008, as a result of the inhaled formulation research expertise of Professor Taylor's team, an earlier Cardiff University spin-out company began trading under the new name of i2c Pharmaceutical Services (i2c) to develop its commercial activities in novel inhaler formulation research and development.
i2c in partnership with the clinical research organisation Simbec Research Ltd, secured several clinical trials relating primarily to i2c's provision of pulmonary imaging which is itself built upon Cardiff's research expertise and methodological advances in clinical scintigraphy.
One of i2c's scintigraphic studies was to evaluate the iNeb® nebuliser which showed that when using the device in Target Inhalation Mode (TIM) as opposed to Tidal Breathing Mode (TBM) it was possible to reduce patient nebulisation times and improve lung deposition. This data is currently used by Philips Respironics and their pharmaceutical partners to promote iNeb® and develop regulatory submissions that use the device.
The diversification of business activities based on Cardiff University's formulation research with HFA propellants, and the increasing global reach of i2c's impact is illustrated by i2c's involvement in a consortium with the pMDI valve manufacturer, Valvole Aerosol Research Italiana (VARI, Italy), and the regulatory support/project management company, Pharmadelivery Solutions (PDS, UK). To date, this consortium has won contracts totalling several million pounds from the United Nations Industrial Development Organisation (UNIDO) with a significant proportion of this investment directed to i2c to reflect its pivotal role.
These contracts are to provide research expertise and technology transfer to assist countries to fulfil their obligations to phase out the use of ozone-damaging propellants in medicinal pMDIs. This research and development allows such nations to comply with the Montreal Protocol while meeting their populations' healthcare demands and developing the capabilities of local pharmaceutical manufacturers. To date, four inhalation products have been developed, approved and transferred to commercial-scale operations in Egypt and Mexico.