PhD student Mohammad Afkhami attended the ESCAPE 24 conference in June 2014 with help from the Simon Wolff Charitable Foundation. Here is his report:
The Simon Wolff Charitable Foundation aided the financing of my travel and accommodation expenses to present my paper as a speaker at the 23rd European Symposium on Computer Aided Process Engineering (ESCAPE 24) held in Budapest from 15th-18th June 2014. I am currently in my final year of a PhD in the Institute of Particle Science and Engineering, School of Process, Environmental and Materials Engineering at the University of Leeds under the supervision of Dr. Ali Hassanpour and Prof. Michael Fairweather.
The demand for insulin is increasing; this is due to the increase in prevalence of type 1 diabetes and particularly type 2 diabetes. Alternative routes of insulin delivery have been tested, these include dermal, oral, buccal, nasal, rectal, vaginal and pulmonary [1-3]. The pulmonary route has proved to be the only method without major disadvantages and is the first clinically effective alternative to subcutaneous insulin. Its earlier use in type 2 diabetes can improve glycaemic control and delay the development of complications [4, 5]. If inhaled insulin is accepted more easily than subcutaneous insulin, and it may be easier to initiate insulin therapy earlier in type 2 diabetes . Moreover, inhaled insulin would be an alternative to patients with needle phobia; there is some degree of needle phobia in at least 10% of the population .
A number of pharmaceutical companies are developing different pulmonary insulin delivery systems . The delivery system has a significant influence on the clinical efficacy. All delivery systems are used to provide regular insulin through the respiratory tract, either in powder form or in solution. The Exubera system developed by Nektar Therapeutics is a dry powder inhaler and has been used by Pfizer. It is the most widely studied pulmonary insulin delivery system available [5, 9, 10]. The powder is present in amorphous form and hence is more stable during storage . Although, a pulse of compressed air is required to deagglomerate the dry powder into an aerosol, this mechanism is very complex and much research is required to fully understand this process . Another difficulty associated with pulmonary drug delivery is in determining the deposition site of the administered dose . Factors that influence the deposition of a drug within the respiratory tract are the physical and chemical properties of the fluid medium and the nature of the aerosol particles.
To achieve an effective drug delivery for dry powder inhalers, dispersion and deposition behaviour of particles in turbulent air should be studied in depth with a view to quantifying the conditions favouring de-agglomeration of powders and delivery by deposition into the lungs airways. In my research I am addressing the process of particle dispersion and deposition in air using computer simulation techniques based on combined large eddy simulation (LES) and a discrete element method (DEM). These methods are applied to study the material properties of single particles and how they relate to the bulk behaviour, including particle dispersion, deposition, and agglomeration, in a horizontal channel. The influences of different particle sizes, surface energies, concentrations, and fluid flow Reynolds number on agglomeration, and the impact of fluid turbulence, are investigated. The agglomeration rate is found to be strongly influenced by these particle and fluid variables, with most of the particle-particle interactions taking place at locations close to the channel walls, aided by the higher turbulence and concentration of particles in these regions.
I selected the most relevant conference to make the greatest impact of our research in the particle technology area. My work aligns with the strategic research goals of the School/Institute in the areas of particle and materials engineering. I attended this conference in computer aided process engineering in Budapest as a speaker in a session which was attended by world leading scientists and engineers in the areas of process and material sciences and engineering, and also industrial representatives from various sectors.
In terms of the work reported, described in a paper included in the peer-reviewed conference proceedings, I presented an important discovery on the conditions that promote particle agglomeration within fluid flows. Attending the conference allowed me to further understand how my work benefits a number of application areas, such as biomaterial, biomedical, energy systems, management and economics, and sustainability of products and processes. It gave me useful feedback on the quality of the work performed, its applicability, and how its usefulness can be further improved through additional work. I am working at the cutting edge of numerical modelling of particle-laden fluid flows, and since numerical modelling and simulation techniques are evolving rapidly attendance at the conference further assisted me in keeping me up to date with the latest developments in these areas. The oral and poster presentations were most beneficial in developing my understanding of other research topics and their applications, two of which, in particular, were of great value to my work; the plenary ‘Progress in PSE applications within the Pharmaceutical Product Life Cycle’ by Prof. Reklaitis which involved the optimization of drug dosage based on the individual patient, and the oral ‘Measurement and Modelling of the Near-field Structure of Large-scale Sonic CO2 Releases from Pipelines’ by Dr. Wareing who presented experiments and simulations performed on the safe design and operation of onshore pipelines for transporting dense phase CO2. The conference provided me with an exceptional opportunity to learn and exchange leading-edge knowledge. As a young researcher, I knew it was important that I network and establish contacts with leading scientists and engineers in the different areas of particle science and numerical modelling covered at this conference as I plan to work in this area on completion of my PhD. I am currently considering postdoctoral research opportunities, and I managed to meet people at this conference and discuss possible opportunities, and was also able to showcase my research. Attendance also provided the opportunity to establish links with other researchers from around the world, and I was delighted to make the acquaintance of many individuals with research interests in common with my own.
I therefore greatly appreciate the financial contribution towards the cost of this conference, and the travel bursary from the Simon Wolff Charitable Foundation was acknowledged in my presentation at the conference.
1. Cefalu, W.T., Evolving strategies for insulin delivery and therapy. Drugs, 2004. 64(11): p. 1149-1161.
2. Shaikh, I., et al., Advanced approaches in insulin delivery. Current pharmaceutical biotechnology, 2005. 6(5): p. 387-395.
3. Heinemann, L., A. Pfutzner, and T. Heise, Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery. Current pharmaceutical design, 2001. 7(14): p. 1327-1351.
4. Barnett, A.H., et al., An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with metformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea. Diabetes Care, 2006. 29(6): p. 1282-1287.
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6. Freemantle, N., et al., Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care, 2005. 28(2): p. 427-428.
7. Hamilton, J.G., Needle phobia: a neglected diagnosis. The Journal of family practice, 1995.
8. Ghosh, S. and A. Collier, Inhaled insulins. Postgraduate medical journal, 2007. 83(977): p. 178-181.
9. Rosenstock, J. Mealtime rapid-acting inhaled insulin (Exubera (R)) improves glycemic control in patients with type 2 diabetes failing combination oral agents: A 3-month, randomized, comparative trial. in Diabetes. 2002. AMER DIABETES ASSOC 1660 DUKE ST, ALEXANDRIA, VA 22314 USA.
10. Quattrin, T., et al., Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes Results of a 6-month, randomized, comparative trial. Diabetes Care, 2004. 27(11): p. 2622-2627.
11. Rave, K.M., et al., Dose response of inhaled dry-powder insulin and dose equivalence to subcutaneous insulin lispro. Diabetes care, 2005. 28(10): p. 2400-2405.
12. LAUBE, B.L., G.W. BENEDICT, and A.S. DOBS, Time to peak insulin level, relative bioavailability, and effect of site of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus. Journal of aerosol medicine, 1998. 11(3): p. 153-173.