UCY-CompSci

SimInhale: a global network of scientists dedicated to improving inhaled drugs

Some exciting outcomes already reported by the group


Most of us have used an inhaler at some point in our life, perhaps after a bad bout of the flu. And with the increasing prevalence of asthma and chronic respiratory conditions we are likely to have people close to us who rely on the long-term use of an inhaler device. But have you ever wondered what goes into the design of these nifty little devices and how well do they actually perform? Can we do any better?

As it turns out, SimInhale, an international network of scientists has been working on answering exactly this type of questions. SimInhale is being funded by the European Commission through the European Cooperation in Science and Technology (COST) program. The SimInhale network counts more than 120 members from around the world, most of them based in the EU, US and Australia. This is a highly multidisciplinary network involving scientists and engineers from Universities and research centers as well as from the industry working in a diverse array of disciplines. SimInhale combines the expertise of specialists in the fields of particle engineering and formulation development, inhaler engineering and design, integrated computer simulations, advanced imaging, patient monitoring and delivery verification, as well as toxicity, risk assessment and regulation. This is not surprising, afterall drug delivery via inhalation is a complex field involving many stages and physical processes. This is in fact the reason that the network has been receiving funding from the European Union: to bring experts from these diverse fields together in order to accelerate progress.

Pulmonary drug delivery is emerging as an important route for administrating therapeutic agents for both topical and systemic therapies. With an aging world population in combination with the reduction of health budgets, one of the greatest challenges is to keep the costs of therapy low. To meet these challenges, medication needs to be affordable yet highly effective and devices have to be easy to operate so that patients are able to comply with correct use and adhere to therapy. These are prerequisites for preventing periodic or permanent exacerbations of pulmonary diseases, which then can lead to greater frequency of hospitalization and thereby, to increased cost of therapy, and may also cause, for instance, development of bacterial resistance against antibiotics. Notably, multi drug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, due to inappropriate therapies, are already a huge global concern.

In this respect, the main challenge in relation to inhaled medicines is to overcome technological challenges while keeping manufacturing costs low, drug administration techniques simple and time needed for administration short.

According to SimInhale's Chair, Professor Stavros Kassinos of the University of Cyprus, an emerging theme in the field is in silico populations studies. "Unless you are talking about drugs with close to 100% lung bio-availability", he says, "regional deposition, that is where exactly the drug particles land in the complex network of airways in the lung, is very important."

"Unless you are talking about drugs with close to 100% lung bio-availability regional deposition, that is where exactly the drug particles land in the complex network of airways in the lung, is very important."

However, a number of practical limitations, such as the desire to avoid exposing patients to unnecessary radiation make the determination of regional deposition in vivo very challenging. That's why determining the factors that influence regional deposition in silico, i.e. using computer simulations, seems such an exciting prospect. In this respect, the availability of very large number of chest CT-scans in medical centers in Europe, the US and elsewhere is a very positive aspect.

These can be used by computational scientists to carry out large-scale simulations using supercomputers and then apply statistical analysis tools to determine those functional or morphological features that influence regional deposition for various groups of patients, for example for asthmatics or COPD patients, etc.

The primary tool used for such computer simulations is what is known as Computational Fluid Particle Dynamics (CFPD). This is a field that emerged in the middle of the previous century, mainly in the context of aerodynamics, and has now reached an impressive level of maturity. Nevertheless, the application of CFPD in inhaled drug delivery applications has a much shorter history, limited to the last 15 years or so, therefore, there are still several open questions related to best practice. Thus, one of the contributions of SimInhale is that it has created a large database of benchmark cases that it will make available to the wider community via open access. The idea is to provide a common platform that scientists all over the world will be able to use to compare computational approaches and tools in order to speed up the process of converging to a small set of best practice guidelines.

"The availability of such a common benchmarks database is an obvious prerequisite to using CFPD in the context of large-scale in silico population studies"

According to Prof. S. Kassinos, "the availability of such a common benchmarks database is an obvious prerequisite to using CFPD in the context of large-scale in silico population studies. It will also be important to provide tools for the verification and uncertainty quantification". All these will be very important in establishing the trustworthiness of in silico population studies and earning acceptance by the regulatory and industrial stakeholders. He continues to add: "we are excited that in SimInhale we are one of the groups that are having an impact towards making in silico population studies for pulmonary drug delivery a reality. This is aligned with the European directives for in silico clinical trials and we think it will have an impact on the field over the next 5 to 10 years."

This is aligned with the European directives for in silico clinical trials and we think it will have an impact on the field over the next 5 to 10 years.

So, next time you or someone you know is using an inhaler think of this group of experts who are working to make these devices even more effective.

More information about the activities of SimInhale can be found at the network's site: http://www.siminhale-cost.eu

Disclaimer: the opinions expressed in this article are the responsibility of the authors and neither COST nor any person acting on its behalf is responsible for use that might be made of the information contained in it.