Conference Program · Bacteriophages and endolysins to tackle respiratory infections caused by superbugs COST is supported by the EU Framework Programme Horizon 2020 Organiser Sponsor

The SimInhale International ConferenceCurrent Challenges and Future Opportunities for

Inhalation Therapies. A cross-disciplinary perspective

30 September – 2 October 2019

Crowne Plaza Hotel, Athens, Greece

Conference Program

OrganisersSponsor

COST is supported by theEU Framework ProgrammeHorizon 2020

08:30 Registration09:15 Welcome by the Local Host

Dr. Stavroula Rozou, ELPEN Pharm.Co.Inc.09:30 Welcome by the SimInhale Chair

Prof. Stavros Kassinos, University of Cyprus09:45 SimInhale - The Big Picture

Prof. Stavros Kassinos, University of CyprusSession 1Chair: Dr. Per Bäckman, Emmace Consulting AB, Sweden

10:00 Plenary LectureThe Microphysics of Aerosol Particle Transformations on InhalationProf. Jonathan Reid, University of Bristol, United Kingdom

10:45 Coffee Break 11:00 Nanotechnologies for lung delivery: lessons from the SimInhale COST Action MP1404

Prof. Elias Fattal, University Paris-Sud, France11:30 WG1 Presentation: Particle engineering/processing of inhaled medicines for local/systemic action

Prof. Alessanda Rossi, University of Parma, Italy12:00 Dissolution testing for orally inhaled products: science, practice and regulation

Prof. Ben Forbes, King’s College London, United Kingdom12:30 An acute regulatory challenge: The need for SimInhale and better in vivo predictions

Dr. Anders Fuglsang, Fuglsang Pharma, Denmark

13:00 Lunch Break14:00 An overview of the COST Programme

Dr. Federica Ortelli, Science Officer, COST AssociationSession 2Chair: Prof. Emeritus Paolo Colombo, PlumeStars srl, Italy

14:30 Plenary LectureBacteriophages and endolysins to tackle respiratory infections caused by superbugsProf. Hak-Kim Chan, University of Sydney, Australia

15:15 Imaging-Assisted Design of a Thermostable and Self-Administrable Tuberculosis Vaccine for InhalationProf. Camilla Foged, University of Copenhagen, Denmark

15:45 WG2 Presentation: Development of a soft mist inhaler using simulation tools to predict lung dose and pharmacokineticsMr. Wilbur de Kruijf, Medspray Pharma BV, The Netherlands

16:15 Coffee Break16:30 Harnessing materials for the development of advanced respiratory therapeutics

Prof. Sally-Ann Cryan, Royal College of Surgeons in Ireland, Ireland17:00 Excipients: their role for respirable particle construction

Dr. Francesca Buttini, University of Parma, Italy 17:30 Day 1 in hindsight 17:45 End of day 1



30 September 2019

08:45 RegistrationSession 3Chair: Dr. Jan Jedelsky, Brno University of Technology, Czech Republic

09:15 Plenary LectureThe Dynamic Airway: Computed Tomography of Airways DiseasesProf. Haiwei Henry Guo, Stanford University Hospital, USA

10:00 Measurement of pulmonary deposition of nanoparticles as a means for morphometry of the distal air spaces and diagnosis of emphysemaProf. Per Wollmer, Lund University, Sweden

10:30 Coffee Break – Group Photo11:00 WG3 Presentation: Dry Powder Inhaler Performance: A CFD-Euler/Lagrange study

Prof. Martin Sommerfeld, Otto-von-Guericke University, Germany11:30 Predicting deposition in the human airways using CFPD: The SimInhale benchmark case

Dr. Pantelis Koullapis, University of Cyprus, Cyprus12:00 Advanced in vitro lung-on-chip platforms for inhalation screening assays

Prof. Josue Sznitman, Technion, Israel 12:30 CFD – DEM simulations of dry powder inhalers. Bridging to reality

Kyrre Thalberg, Inhaled Product Development, Pharmaceutical Technology & Development, AstraZeneca Gothenburg, Sweden

13:00 Lunch Break

Session 4Chair: Dr. Katrin Bauer, TU Bergakademie Freiberg, Institute of Mechanics and Fluid Dynamics, Germany

14:00 Plenary LectureThe Role pf Lymphatic growth and remodeling in Chronic Respiratory DiseasesProf. Stanley Rockson, Allan and Tina Neill Professor of Lymphatic Research and Medicine, Stanford University School of Medicine, USA

14:45 Aerosol characterization for the development of novel inhalation devices: in-vitro experimentsDr. Nicolas Schwenck, PARI, Germany

15:15 WG4 Presentation: Experimental methods applicable in research of flow and aerosol deposition in human airways and their replicasDr. Frantisek Lizal, Brno University of Technology, Czech Republic

15:45 Coffee Break16:00 Understanding inhaled drug delivery using in silico and in vitro methods: Case studies involving inhaler

and simplified or realistic human airway geometries Dr. Fotos Stylianou, University of Cyprus, Cyprus

16:30 STSM oral presentation: DPI mishandling: Influence on in-vitro drug deposition, dissolution and pharmacokineticsSnezana Radivojev, Research Center Pharmaceutical Engineering, Medical University of Graz, Austria

16:45 STSM oral presentation: Molecular Modelling to Design/Characterize Hyperbranched Polymer Nanoparticles Employed as Delivery Systems or Therapeutic Agents in NanomedicineProf. Marco Agostino Deriu, DIMEAS, Politecnico di Torino, Italy

17:00 Day 2 in hindsight

17:15 MC Meeting (Only MC Members)



1 October 2019

08:45 Registration

Session 5Chair: Prof. Gerrit Borchard, University of Geneva, Switzerland

09:15 Plenary LectureBiopharmaceutical Classification of Inhaled MedicinesDr. Jayne E. Hastedt, JDP Pharma Consulting LLC, USA

10:00 Inhaled drug product development and commercializationDr. Aditya Das, Pharmaceutical Consulting LLC, USA

10:30 Coffee Break

10:45 ‘Trying but failing’: medication delivery via inhalers- Let’s leave no one behindProf. Maria Cordina, Department of Clinical Pharmacology and Therapeutics,University of Malta, WHO Collaborating Centre for Health Professionals Education and Research

11:15 Efflux Transporters in the LungDr. Carsten Ehrhardt, Trinity College Dublin, Ireland

11:45 Intelligent Clinical Platform for Self-management, Training, and Support of Chronic Respiratory PatientsDr. Antonios Lalas, Information Technologies Institute, Centre for Research and Technology Hellas (CERTH), Greece

12:15 Roundtable Panel Discussion and Conclusions

Moderators: Dr. Stavroula Rozou, ELPEN Pharm.Co.Inc., GreeceDr. Dimitrios Rekkas, National and Kapodistrian University of Athens, GreeceDr. Aditya Das, Pharmaceutical Consulting LLC, USA

1. The role of in silico modeling: towards whole-lung hybrid models, gaining wider regulatory acceptance (20 min)Introductory statements by Dr. Bo Olsson (Emmace Consulting AB, Sweden) and Prof. Josue Sznitman (Technion, Israel)

2. Personalized therapies: patient-specific vs patient-group specific...And what is the role a digital inhaler? (20 min) Introductory statements by Mr. Wilbur de Kruijf (Medspray Pharma BV, The Netherlands), Prof. Stavros Kassinos (University of Cyprus) and Dr. Antonios Lalas (CERTH, Greece)

3. Emerging Challenges and Opportunities: Old diseases revive. Repurposed/repositioned drugs. (20 min)Introductory statements by Dr. George Ismailos (ELPEN Pharm.Co.Inc., Greece) and Dr. Stavroula Rozou (ELPEN Pharm.Co.Inc., Greece)

13:15 Farewell Light Lunch

14:00 End of conference



2 October 2019





Plenary Speakers

Organiser

Sponsor


Prof. Hak-Kim ChanUniversity of Syndey

Australia

Prof. MD. Haiwei Henry Guo Stanford University Hospital

USA

Dr. Jayne HastedtJDP Pharma Consulting LLC

USA

Prof. Jonathan ReidUniversity of Bristol

United Kingdom

Prof. MD. Stanley Glenn RocksonThe Allan and Tina Neill Professor of Lymphatic Research

and Medicine / Stanford University

USA

Short CVHak-Kim Chan, Professor in Pharmaceutics, is leading the Advanced Drug Delivery Group and the RespiratoryResearch Theme at the Faculty of Pharmacy, University of Sydney, Australia. Graduated from the University ofSydney (Ph.D. 1988 and D.Sc. 2009), he was a postdoc at the University of Minnesota and a scientist atGenentech Inc. His research focuses on inhalation drug delivery, ranging from aerosol formulation and inhalerdevice to scintigraphic imaging of lung deposition and clinical outcome. He played a pivotal role in thedevelopment of inhaled mannitol products Aridol™ (approved in the USA) and Bronchitol (approved in theEU) for bronchoprovocation and mucus clearance, respectively. He has over 400 scientific publications onpharmaceutical formulation and drug delivery (including 300 original research papers, 85 book chapters andreviews and 60 full-length conference articles, with over 13,400 citations and h-index 66) and holds tenpatents in these areas. He is an executive editor of Advanced Drug Delivery Reviews and on the editorialadvisory boards of various pharmaceutical journals. He is a Fellow of the American Association ofPharmaceutical Scientists (AAPS), Fellow of Royal Australian Chemical Institute (RACI), and was Chair of theNSW Pharmaceutical Science Group of the RACI, and Vice President of the Asian Federation forPharmaceutical Sciences.

Abstract Respiratory infection caused by multidrug-resistant (MDR) Gram-negative bacteria (‘superbugs’) is a majorhealth problem worldwide. Bacteriophages (‘bacteria-eaters’) have been documented to be efficaciousagainst MDR bacteria with minimal side effects. In addition, endolysins are enzymatic proteins derived fromphages with strong antibacterial properties. However, intravenous administration of these biologics may notbe very effective against lung infections, as degradation and clearance in the systemic circulation occur beforethey can reach the infected respiratory tract. Inhalation administration for respiratory infection are thusemerging as a promising alternative route. We have successfully produced liquid and powder aerosolssuitable for respiratory delivery of phages and endolysins. The powder formulations of phages were shown tobe stable, highly dispersible and inhalable, and capable of killing ‘superbugs’ in the lungs of infected animals.With no new effective antibiotics being in the development pipeline for the life-threatening infections causedby Gram-negative ‘superbugs’, our study provides the much-needed formulation and pharmacologicalinformation on inhalation delivery for fast-tracking translational research into a new therapy.



30 September – 2 October 2019, Crowne Plaza Hotel, Athens, Greece

http://www.siminhale-cost.eu/conference

Prof. Hak Kim Chan

University of Sydney, Australia

Bacteriophages and endolysins to tackle respiratory

infections caused by superbugs


Organiser Sponsor

Short CVH. Henry Guo is a clinical associate professor in radiology and nuclear medicine at Stanford School of Medicine. Hereceived his undergraduate degree at Massachusetts Institute of Technology, followed by MD and PhD in the medicalscientist training program at the University of Washington in Seattle, where he concentrated on directed evolution of DNArepair proteins and carcinogenesis. He did a 5-year residency in diagnostic radiology, followed by fellowships in nuclearmedicine and thoracic imaging at Stanford University Hospital, where he has been faculty physician for the past six years.

Henry specializes in imaging of lung diseases, and spends 70% of his time interpreting imaging scans of patients orderedprimarily through pulmonary and critical care medicine and oncology. Some of the airways diseases imaged include:bronchiectasis, tracheobronchomalacia, asthma, chronic infections, and cystic fibrosis. His research interests focus onimproving understanding of diseases through high resolution anatomical and molecular imaging; and exciting directionsfor future of thoracic radiology are ultra-low dose, quantitative, and dynamic CT. For example, in the study of largerairways diseases, Henry has published on CT scanning methods to identify dynamic collapse of large airways. For smallairways diseases, his group has recent published papers on using quantitative CT data analysis to improve diagnosis ofbronchiolitis obliterans graft-versus-host lung disease. Henry adapts developing technologies to enhance radiologists’capabilities, including using machine learning algorithms for automated cardiac chamber quantification in cardiacarrhythmias and pulmonary hypertension classification. He is using 3-D printing techniques to recreate lung diseases, suchas of early lung cancer nodules for CT scanner quality assurance, tailoring patient specific treatment planning models, andcreating disease models for medical education. He has received awards including the Society of Thoracic Radiologyresearch grant, and junior faculty educator of the year by Stanford radiology residents.

Abstract Anatomic illustrations depict the lungs and airways in a static state, and this fixed view is further reinforced by mostclinical chest imaging, with chest radiographs and computed tomographs (CTs) being obtained with the patient in staticend-inspiration. Of course, the lung is a dynamic organ that is dependent on continuous movement of gas, blood, mucous,and lymphatic flow to carry on the respiratory process essential to life. Air flows in and out of the upper respiratory tract,down to alveolar spaces, while blood circulation depends on orderly passage through the pulmonary capillary beds for gasexchange. Foreign particles and infectious agents are cleared by the mucociliary escalator, cough, and lymphatics. Diseasesof the lung arise when the normal physiologic movements are disrupted or become out of bounds. In this talk I will focuson using CT scanning to capture the lungs in different phases of its function, and how alterations in normal biomechanicsare accentuated by imaging of the lungs and airways in non-end-inspiratory states. I will focus on large airways diseasessuch as tracheobronchomalacia, relapsing polychondritis, chronic infections, and granulomatosis with polyangiitis (GPA),and small airways disease including bronchiolitis obliterans, asthma, and chronic bronchitis, in order to provide a clinicalperspective of airways diseases. Learning Objectives: 1). Technical parameters of multi-phasic CT. 2). Pathophysiology ofairways diseases. 3). Imaging manifestations of pathologic processes. Combining clinical understanding and engineeringexpertise can enhance development of effective treatments.





Prof. MD. Haiwei Henry Guo

Stanford University Hospital, USA

The Dynamic Airway: Computed Tomography of Airways

Diseases


Organiser Sponsor

Short CVDr. Jayne E. Hastedt has over 35 years of experience in pharmaceutical product development. She has had managementand technical leadership responsibilities for the development of small molecules, peptides, and proteins using variousdosage forms, routes of delivery, and technologies and has supported successful US and European regulatory productapprovals. Her experience includes leading physicochemical characterization and CMC development activities spanningearly drug product development through product registration and launch. She has supported the development of oral,transdermal, oral controlled release, and inhaled drug delivery dosage forms. She is currently co-leading an initiativewithin the PQRI BTC to develop a BCS-like classification system for inhaled medicines. Dr. Hastedt is the Managing Directorof JDP Pharma Consulting, LLC and throughout her career, she has had the opportunity to work at ALZA, Inhale,Glaxo/Glaxo Wellcome, and Boehringer Ingelheim. She received her MS and PhD degrees from the University of Wisconsin– Madison School of Pharmacy and holds adjunct faculty positions at the UW School of Pharmacy and the University ofthe Pacific. Dr. Hastedt is also an Editor for the AAPS Open journal.

Abstract In the mid 1990s, a biopharmaceutical classification system was developed for oral immediate release drug products (theBCS). The BCS classification system for oral drugs was developed based on in vitro biorelevant drug physicochemical andproduct properties. Formulators gain an understanding of CMC product development challenges and opportunities simplybased on the location of the drug substance within the BCS grid. Discovery chemists use the grid attributes to fine tunethe properties of new chemical entities. Also, based on the specific BCS classification, biowaivers may or may not begranted and the IVIVC potential of an oral immediate release product can be assessed.In 2018, the Product Quality Research Institute (PQRI) approved an effort to support the development of a classificationsystem for inhaled medicines (an iBCS). The goal of this effort is to develop a physiologically based classification systembased on biorelevant drug and product attributes for pulmonary drugs. Such a system would provide a set of tools to aidepulmonary drug development efforts and, as with the oral BCS, would identify CMC-based product development technicalrisks. Ultimately the longer-term goal of the development effort is to use the classification system to supportbioequivalence assessments of inhaled medicines.This presentation will describe the iBCS development approach and challenges and provide an update on the progressmade to date, including preliminary classification grids and the modeling studies being used to set the grid boundaries.





Dr. Jayne E. Hastedt

JDP Pharma Consulting, LLC, USA

Biopharmaceutical Classification of Inhaled Medicines


Organiser Sponsor

Short CVJonathan Reid is Professor of Physical Chemistry at the University of Bristol and current President of the UKand Ireland Aerosol Society. His research is focussed on understanding the microphysics of aerosol processesusing a range of single particle techniques to capture, manipulate and probe the dynamics of processes suchas condensation and evaporation using light scattering and spectroscopy. Research underway in his groupspans projects in environmental and atmospheric aerosols, drug delivery to the lungs, the airbornetransmission of disease and formulation science (e.g. droplet drying and spray drying). He is director theEngineering and Physical Sciences Research Council Centre for Doctoral Training in Aerosol Science, a centrethat includes participants from 7 universities in the UK and approximately 50 industrial and public sectorpartners. Jonathan is the past recipient of the Royal Society of Chemistry (RSC) Corday-Morgan medal (2013),the Marlow medal of the Faraday Division (2004) and the Harrison Memorial medal (2001).

Abstract Aerosol particles are extremely dynamic, responding rapidly to changes in their environment. Measurementsof aerosol microphysics and the processes that occur at the level of individual particles can improve ourunderstanding of what happens to the aerosol between the point of aerosol generation (e.g. from a metereddose inhaler or nebuliser) and deposition within the respiratory tract, and during inhalation[1]. Followinggeneration, aerosol particles may rapidly lose propellants and solvents, leading to changes in particle size andcomposition. They may respond to the local humidity of the environment, either losing or gaining waterdepending on the relative humidity. Once inhaled into the humid environment of the lung, liquid dropletsmay absorb water on timescales similar to inhalation, growing to a size many times their initial size. This couldimpact on their deposition pattern in the lung. For dry powders, particles may adsorb water leading todissolution and changing their physical state.Using refined experimental tools, I will describe state-of-the-art measurements of the dynamics of individualparticles including the evaporation of propellants and solvents, the condensation of water onto liquid andamorphous particles, and the timescales for dissolution of crystalline particles[1,2]. We will also consider howthe viscosity, surface tension, hygroscopicity and phase of aerosol particles can be controlled and tailored togive a desired outcome in response to a change in the surrounding water vapour.

[1] A.E. Haddrell, D. Lewis, T. Church, R. Vehring, D. Murnane and J.P. Reid, 'Pulmonary Aerosol Delivery and the Importance of GrowthDynamics', Therapeutic Delivery 8 (2017) 1051–1061.[2] A. Farkas, D. Lewis, T. Church, A. Tweedie, F. Mason, A.E. Haddrell, J.P. Reid, A. Horvath and I. Balashzay, 'Experimental andcomputational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler', International Journal ofPharmaceutics 533 (2017) 225-235.





Prof. Jonathan Reid

University of Bristol, UK

The Microphysics of Aerosol Particle Transformations on

Inhalation


Organiser Sponsor

Short CVDr. Rockson is the Allan and Tina Neill Professor of Lymphatic Research and Medicine at Stanford UniversitySchool of Medicine. After earning his medical degree from Duke University School of Medicine, Dr Rocksoncompleted his internship and residency training in internal medicine at Brigham and Women’s Hospital ofHarvard Medical School, in Boston, Massachusetts, and fellowship training in the cardiac unit ofMassachusetts General Hospital, Harvard Medical School. He is a fellow of the American College ofCardiology, Society of Vascular Medicine, American College of Angiology, and American College of Physicians,as well as a member of the International Society of Lymphology, American Society of Internal Medicine, andthe Paul Dudley White Society, among others. As a principal investigator or co-investigator, he has beeninvolved in numerous clinical trials researching various aspects of lymphatic disease, vascular biology andcardiovascular medicine. His basic research involves the investigation of disease pathogenesis andidentification of biomarkers of lymphatic diseases, as well as research into molecular and pharmacologictherapeutics. As a Professor of Medicine, Dr. Rockson serves concurrently as the Stanford’s Chief ofConsultative Cardiology and the Director of the Stanford Center for Lymphatic and Venous Disorders. Dr.Rockson is Editor-in-Chief of Lymphatic Research and Biology and sits on the editorial board of Angiology. Dr.Rockson works closely with National Institutes of Health, in an advisory capacity, to advance the agenda forlymphatic research. He has been a frequent invited lecturer at national and international meetings,congresses, and societies. He is a co-founder of the Lymphatic Education and Research Network (LE&RN) andhas served as Chair of the inaugural Gordon Research Conference, entitled ‘Molecular Mechanisms inLymphatic Function and Disease’. He is the co-author of Lymphedema: A Concise Compendium of Theory andPractice now in its second edition. Dr. Rockson has authored more than 200 scientific papers, reviews, bookchapters and books devoted to various aspects of lymphatic biology and disease, vascular biology, andcardiovascular medicine.

Abstract Lymphatics proliferate, become enlarged, or regress in inflammatory lung diseases in humans. Lymphaticgrowth and remodeling is known to occur in the mouse trachea in sustained inflammation and may thereforeplay a role in chronic respiratory diseases, including asthma. The relevant biology of normal and abnormallymphatic vascular growth will be reviewed in the context of this phenomenon.





Prof. Stanley Glenn Rockson MDThe Allan and Tina Neill Professor of Lymphatic Research and Medicine

Stanford University, USA

The Mechanistic Role for the Lymphatic Vasculature in Chronic

Respiratory Disease


Organiser Sponsor





30 September Speakers

Organiser Sponsor


Dr. Francesca ButtiniUniversity of Parma

Italy

Prof. Elias FattalUniversity Paris-Sud

France

Prof. Ben ForbesKing’s College London,

United Kingdom

Prof. Stavros KassinosUniversity of Cyprus

Cyprus

Dr. Federica OrtelliCOST Office

Prof. Sally-Ann CryanRoyal College of Surgeons

in IrelandIreland

Prof. Camilla FogedUniversity of Copenhagen

Denmark

Dr. Anders FuglsangFuglsang Pharma

Denmark

Wilber de KruijfMedspray Pharma BV

The Netherlands

Prof. Alessandra RossiUniversity of Parma

Italy

Short CVFrancesca Buttini is currently holding an Associate Professor position at the Department of Pharmacy, University ofParma (IT) where she got the PhD title in 2004 and where now she is leading the unit dedicated to design ofpharmaceutical products for inhalation. In 2014, she was appointed as Visiting Lecturer at the Institute ofPharmaceutical Science of King’s College London (UK). In 2016 she has been affiliated as Key Researcher at theResearch Center Pharmaceutical Engineering (Austria). She was awarded as best emerging scientist by aerosol UKsociety in 2017.She works on the development of innovative pulmonary products such as solutions for nebulisation and metered doseinhalers, but her main research area is the formulation and testing of dry powder inhalers. She is an expert both inparticle engineering and in development of carrier-based formulations and several of her works were focused on theconstruction of antibiotic particles.Up to date, she has published 55 original papers, 5 book chapters and 4 patents in the field of drugs and drug deliverysystems and in the last years she received more than 25 invitations to lecture at international conferences.Dr Buttini collaborates with many international institutions and with multiple pharmaceutical companies active in thedevelopment of pulmonary medicinal products. Finally, in 2013 Francesca is a founder of PlumeStars, an innovativeStartup, dedicated to development of orphan drug products to treat lung and systemic disease by inhalation therapy.

Abstract This talk is focused on the analysis of the excipient role in inhalation products. Excipients are inactive ingredients thatare intentionally added to therapeutic products but are not intended to exert therapeutic effects at the intendeddosage, although they may act to improve product delivery or efficacy. The Food and Drug Administration (FDA, 2009)favors the use of commercially established excipients as well as “generally recognized as safe” (GRAS) substances.The current excipients approved for respiratory drug delivery are very limited in number. Mechanical and functionallung safety has not to be affected by inhaled foreign substances. In dry powder inhaler DPI, most of the formulationscontain excipients as carrier particles and lactose is the most commonly used excipient in marketed DPIs. Additional orternary component can be added to increase the release and respirable fraction of the active drug. In this talk the roleof magnesium stearate, used to enhance particle detachment from lactose surface will be presented.Beside carrier-based formulations, most particle engineering approaches tend to require formulation excipients inorder to enhance both the particle population aerodynamic characteristics and preserve chemical structure in the caseof the biotherapeutic. A wide range of formulation excipients have been shown to enhance inhalation powderformulations. However the amount of excipient used should be limited as much as possible in order to reduce theamount of powder to inhale.Despite improvements in inhalation powder formulations with current particle engineering technologies, precisecontrol of particle size and morphology for the optimization of dose uniformity and lung deposition remains achallenge.






Organiser Sponsor

Dr. Francesca Buttini

University of Parma, Italy

Excipients: their role for respirable particle construction

Short CVProf. Sally Ann Cryan is Professor of Drug Delivery, Principal Investigator in the Tissue Engineering ResearchGroup and Research Lead in the School of Pharmacy in the Royal College of Surgeons in Ireland (RCSI). Herresearch group focuses on translational drug delivery, pharmaceutical engineering and the development ofnovel materials for healthcare applications. Her team has developed innovative particle engineeringstrategies for drug targeting tuberculosis, cystic fibrosis and cancer. Her work also includes delivery oftherapeutic molecules and cell-based therapies within scaffolds for regenerative medicine applications with afocus on orthopaedic, cardiovascular and respiratory tissue engineering. Working with polymer chemists herteam have developed a suite of advanced nanotechnologies and hydrogels for healthcare applicationsincluding printable biomaterials. She has fild a number of patent applications and has over 150publications/presentations in peer-reviewed and professional journals and edited conference proceedings.She works extensively with the pharmaceutical and medical device industry in the areas of drug productdevelopment and pharmaceutical technology.

Abstract Respiratory diseases are among the leading causes of morbidity and mortality worldwide and new treatmentsfor a range of respiratory pathologies are urgently required. With a growing number of small molecules,biomolecules and cell-based therapies in the drug pipeline for respiratory pathologies, a number of keyscientific and industrial challenges have limited their translation to-date including (1) an efficient deliverymethod (2) control of the fate of the therapeutic cargoes once delivered to the lungs and (3) inadquate toolsand models for their clinical and commerical translation. Approproiate materials-based delivery systems havethe potential when combined with the appropriate device to address these key issues. We have designed andmanufactured microparticle-based systems for targeting anti-tubercular agents to the site of TB infection inthe lungs1. Our team is also developing a range of innovative platforms for controlled delivery of gene- andcell-based therapies targeting inflammatory lung diseases2,3. We have harnessed advanced high contentanalysis methods to screen the nano- and microparticle technologies and in addition, we are using tissue-engineering approaches to design 3D scaffolds of the airways4 as a much needed tool for respiratory drugdevelopment and as the basis for regenerative therapies.





Prof. Sally-Ann Cryan

Royal College of Surgeons in Ireland

Harnessing materials for the development of advanced

respiratory therapeutics


Organiser Sponsor

Short CVElias Fattal is a full professor in Drug Delivery Science at the University of Paris-Sud in Châtenay-Malabry, France andhas been President of APGI from 2003 to 2010. He received his Pharmacy Degree (1983) and Ph.D. (1990) from theUniversity of Paris-Sud and followed an internship in Hospital Pharmacy at the University of Lille (1984-1986). Aftervisiting the Department of Pharmaceutical Chemistry at the University of California, San Francisco for a post-doctoral position (1990-1991), he became Associate Professor (1992) and full Professor at the University of Paris-Sud (2000). He is heading the Institut Galien Paris-Sud. Over the past 25 years, he has made fundamental andapplied contributions to the fields of drug delivery using nanotechnologies for targeted or local delivery of drugsand nucleic acids. He has been mostly focusing on lung nanotoxicity as well as the design of nanoparticle-baseddelivery systems for the delivery of anti-inflammatory drugs and nucleic acids.He has issued 14 patent families.Several of his inventions have been licensed to the pharmaceutical industry. He has been involved in thedevelopment of an adjuvant to antibiotics able to reduce resistance by adsorbing residual colonic antibiotics(clinical phase II). One of his patents led to Calixarene® Cevidra, a cream for the treatment of external actinidecontamination. Prof. Fattal has authored more than 250 refereed articles and 30 book chapters. He has received thePharmaceutical Sciences World Congress (PSWC) Research Achievement (2007), the controlled Release Societyfellow Award (2016), was awarded in 2016 by the French Academy of Sciences for his research at the interface ofchemistry and biology and more recently in 2018 received the Maurice-Marie Janot Award. He serves in theeditorial board of 8 scientific journals.

Abstract During the last two years, one of the working group from COST Siminhale has attempted to produce an analysis ofthe state of the art in the field of inhaled nanomedicine. The conclusions have been established in a position paper.The main points raised are the following:• There are many different particles designed for lung delivery and it is very difficult to provide a clear idea on

which type of particles is the most suited. We believe that it is a combination of physicochemical properties,deposition ability and good safety that will be the driving force for the development of such delivery systems.Other parameters are still under discussion such as macrophage uptake, penetration into the mucus orinteractions with lung surfactant.

• In most cases, nanoparticles seem appropriate for modified drug release, lung targeting, and retention.However, there is a need for deeper insight into nanoparticulate-drug pharmacokinetics in order to have acomplete image of their real potentialities.

• In terms of safety, it seems that the most popular type of particles (SLN, liposomes, PLGA nanoparticles) doesnot induce any toxicological effects. However, it is very important to evaluate the chronic toxicity of thesenanoparticles.

The presentation, through specific and recent experimental pieces of evidence, will attempt to sum up the state ofthe art in the field of nanomedicines for lung delivery.






Organiser Sponsor

Prof. Elias Fattal

University Paris-Sud, France

Emerging inhaled nanomedicines and associated excipient

technologies: What did we learn from COST Siminhale?

Short CVCamilla Foged is Professor of Vaccine Design and Delivery at the Department of Pharmacy at University ofCopenhagen (since 2018), Denmark. Her main research area is advanced drug delivery, in particular design of newvaccine and nucleic acid delivery systems to improve therapy. Drug delivery challenges are addressed using state-of-the-art technologies, and this has fostered innovative solutions and high-impact publications in drug delivery. Herresearch goal is to improve disease prevention and treatment in the fields of infectious and inflammatory diseasesand cancer. These aims are approached by imaging-guided design of nanoparticle-based vaccine and nucleic acidformulations, and she engages in research projects spanning from early discovery phase projects to first-in-manclinical studies. She is widely recognized nationally and internationally in the field of drug delivery, and she has awell-established and extensive network of national and international collaborators in academia and industry. Herresearch has been funded with more than EUR 7 million via prestigious and highly competitive grants. She has anMSc in Biochemistry from University of Copenhagen (1998), and she attained her PhD in Pharmaceutics in 2003 fromThe Danish University of Pharmaceutical Sciences. Prof. Foged has edited one book about subunit vaccine delivery,and she has (co)authored more than 105 scientific papers/book chapters and 150 conference abstracts at nationaland international conferences.

Abstract Tuberculosis (TB), caused by infection of the lungs with Mycobacterium tuberculosis, is a major global killer, andcurrent treatment options with antibiotics are severely challenged by the occurrence of drug resistant andextensively drug resistant bacterial strains. Although the old Bacillus Calmette-Guérin (BCG) vaccine exists fortuberculosis vaccination, it confers highly variable protection for adolescents and adults. A promising strategy forachieving life-long immunity to TB is to revaccinate BCG-vaccinated adults with an inhalable dry powder-based TBvaccine, which is self-administrable and independent of an expensive cold-chain. We have made a majorbreakthrough by identifying the necessary molecular components for such an efficient and thermostable inhalableTB subunit vaccine (antigen, adjuvant and stabilizing excipients for drying), but a number of important scientificquestions have to be addressed before the potential of this vaccine can be fully realized. This presentation focusseson how we solve fundamental scientific and technical preclinical challenges necessary for the further design andprogression of the TB vaccine from the preclinical stage to clinical testing. In particular, I will focus on how we havecombined formulation design, particle engineering and device technology with imaging techniques in preclinicalanimal models to generate knowledge enabling us to reach and define the specific areas in the lungs, which areoptimal for vaccine deposition, efficacy and safety. Such knowledge will contribute significantly to increasing ourunderstanding of the basic requirements for safely stimulating protective mucosal immunity in the lungs and toprogressing TB vaccine research. A personalized and self-administrable thermostable vaccine that can be mass-distributed to e.g. the developing world might in the long-term have a tremendous impact on global health.






Organiser Sponsor

Prof. Camilla Foged

University of Copenhagen, Denmark

Imaging-Assisted Design of a Thermostable and Self-

Administrable Tuberculosis Vaccine for Inhalation

Short CVBen Forbes is Professor of Pharmaceutics at King’s College London. He has a BPharm from King’sCollege London (1987) and a PhD in Drug Delivery from Strathclyde University (1996). Before doctoralstudies, he worked in hospital pharmacy in London and Sydney, and for Inveresk Clinical Research inEdinburgh. He was appointed to the academic staff of King’s College London in 1997 and is a registeredpharmacist in the UK. The term ‘Inhalation Biopharmaceutics’ was coined by Professor Forbes in thedying embers of the last Millennium to describe the scientific field that considers the factors thatinfluence respiratory and systemic exposure to inhaled drugs [Ehrhardt C, Pharm Res 34: 2451–2453,2017]. Professor Forbes has authored many publications in this area, including: (1) inhaled medicineformulation, (2) the development and application of techniques to study respiratory drug transport andmetabolism, (3) inhalation toxicology. He chairs the Scientific Advisory Committee of the AerosolSociety’s annual Drug Delivery to the Lung’s (DDL) conference.

Abstract Dissolution testing is routinely used to predict or evaluate the performance of pharmaceutical productsand for quality control purposes. Although a variety of standardized dissolution test methods areavailable for solid dosage forms, to date there is no universally accepted method for estimating thedissolution of inhaled products. There is, however, an emerging consensus that dissolution may be acritical quality attribute for certain inhaled products and a number of scientific studies have attemptedto establish the relationship between the dissolution of inhaled aerosols and the rate and extent of drugabsorption. This interest has led to the development of a wide range of in vitro dissolution systems,although none has been established as the preferred choice for dissolution testing for inhaled products.Designing and implementing a dissolution method relevant for inhaled drug delivery is challengingbecause key features of aerosol deposition and the environment in the respiratory tract after particledeposition are difficult to replicate in vitro. For example, it is necessary to collect a relevant aerosolfraction, introduce it to an appropriate dissolution medium and determine the release of a small massof drug over time. The dissolution of inhaled products has been discussed in various fora by bodies suchas the US FDA, USP, IPAC-RS, PQRI and projects have been sponsored with the aim of exploring whatrole dissolution might play in assuring the efficacy, safety and quality of aerosol medicines.






Organiser Sponsor

Prof. Ben Forbes

King’s College London, United Kingdom

Dissolution testing for orally inhaled products: science,

practice and regulation

Short CVAnders Fuglsang graduated in 1998 from the Royal Danish School of Pharmacy, Copenhagen, spending part ofhis studies at Leiden University, in the Netherlands. He was awarded his PhD in 2002 specialising incardiovascular pharmacology. Following work as an Assistant Professor, he worked as a consultant for anumber of Originator Pharmaceutical companies at a brand optimisation company in Copenhagen. In 2005,he joined the Norwegian Medicines Agency as a Clinical Assessor and became Expert Advisor to the WHO andmember of the Efficacy Working Party at the EM(E)A. He was Chair of the sub-group for Orally InhaledProducts which published the 2009 guideline on Therapeutic Equivalence for inhalation products (still inforce), and was also a member of the PK-subgroup. Other duties included provision of Expert ScientificAdvice, GLP/GCP-inspection and -training, and responsibility for Assessor Training for Inhaled Products at theEM(E)A. Through 2009 to September 2010, he was Clinical and Regulatory Strategy Manager at a worldleading generic company.He owns the consultancy, Fuglsang Pharma. He is the author of 40+ papers in the fields of Pharmacokinetics,Generics, Genetics and Pharmacology, and is a reviewer for some 15+ international journals includingScience, Trends in Genetics and Drug Discovery Today. Present and former clients include the World HealthOrganization, USP, pharmaceutical companies, management firms and investment banks.

Abstract Asthma and chronic obstructive disease are heavy burdens to health care systems and are associated withincreased mortality and lowered quality of life for patients. There is a dire need to improve treatmentopportunities and to introduce cost-effective alternatives. Regulatory guidelines are in place, intellectualproperty is not a barrier, so numerous companies are or have been developing the products. Yet, 90% of themare failing and do not get beyond the in vivo stages. The failures are rarely published, so the literature in thearea is not reflective of what works in practice. This talk highlights the typical steps companies are taking todevelop these products, and highlights a single element that almost all companies are now relying on andwhich more often than not is associated with failure. The talk questions the ethics associated with uncriticaluse of this approach. The talk aims to illustrate how activities under the SimInhale initiative could solve oneof the industry's biggest problems thereby contributing to improved the quality of life for patients sufferingfrom respiratory disease.





Dr. Anders Fuglsang

Fuglsang Pharma

An acute regulatory challenge:

The need for SimInhale and better in vivo predictions


Organiser Sponsor

Short CV

Dr Stavros Kassinos is Professor in the Department of Mechanical and Manufacturing Engineering at the University of Cyprus and the Head of the Computational Sciences Laboratory at the University of Cyprus (UCY-CompSci). He serves on the Editorial Boards of the International Journal of Heat and Fluid Flow, Flow Turbulence and Combustion (FTaC) and Heliyon and is the Chair of COST Action MP1404 – Simulation and pharmaceutical technologies for advanced patient-tailored inhaled medicines (SimInhale). He completed his undergraduate studies at the University of Texas at Austin while on a CASP/USIA scholarship (1987) followed by graduate studies in Mechanical Engineering at Stanford University in California (M.Sc. 1989, Ph.D. 1995). His research interests center on the numerical simulation and modeling of complex physical systems including turbulent fluid-particle flows in connection with environmental, biomedical and technological applications. In particular, he is interested in the further development of in silico methods in support of inhaled drug development.

Abstract

Four very busy years have passed quickly have since the launch of COST ActionMP1404 – “SimInhale”. The SimInhale conference taking place at the end of September2019 in Athens will offer us the opportunity to showcase to the community at largesome of the best examples of our collaborative work within the “SimInhale”community. It is also a time to reflect on some of the lessons learned and the problemsthat remain open in inhalation and provide an opinion at some of the directions thatwe, as a research community, need to turn our attention to in the coming years






Organiser Sponsor

Prof. Stavros Kassinos

University of Cyprus

SimInhale - The Big Picture

Short CVWilbur de Kruijf is responsible for new business development at Medspray Pharma, the Netherlands. Medspray developsnovel metered dose liquid inhalers and eye spray devices, based on their proprietary micro nano technology spray nozzles.Wilbur joined Medspray thirteen years ago to start up device development in collaboration with Medspray’s devicepartners. Wilbur (born in 1971) has a background in Industrial Design Engineering (M.Sc. Design Engineering 1995, M.Sc.Advanced Industrial Design Engineering 1997, Delft University of Technology) with further specialisation in medical devicedevelopment (acc. ISO 13485), design for six sigma and user centred design. Before joining Medspray, Wilbur previouslyworked for a Dutch design consultancy firm, Indes, where he has won several international design and usability awards forhomecare & rehab products and hospital equipment. Wilbur is currently the work group leader of ‘WG2 - inhalationdevices’ of Cost Action SimInhale and he is the secretary of the Dutch medical aerosol scientist network ‘MAD Foundation’.

Abstract In this presentation, the development of a novel soft mist inhaler device will be described, from ideation, feasibility,design, tooling, design verification, up to the first clinical trial results. The focus will be on in-vitro-in-vivo-correlation. Thedevice is expected to enter the market in 2022. It is a mechanical multi-dose soft mist inhaler driven by a spring, nobatteries, no propellant, just a water-based formulation without preservatives.Medspray generally uses data from the in-vitro testing of the device prototypes to assist their Pharma customers to predictthe outcome of the clinical studies regarding lung dose and pharmacokinetics. In the lecture several in-vitro set-ups withrealistic throat models and idealized throat models will be discussed, as well as the use of Mimetikos Preludium softwarefrom Emmace consulting.Both Emmace (particularly Bo Olsson, Per Bäckman and Mårten Svensson) and Medspray have been active members of theCost Action Siminhale and their collaboration has intensified over the course of the action, the recent 4 years.Medspray is inventor and manufacturer of innovative spray nozzles and inhalation & spray devices based on those nozzles.Located at ‘Kennispark’, the business and science park of Twente University in the Netherlands, Medspray uses nanotechnology to create spray nozzles from silicon with tiny orifices (approximately 2 micrometer in diameter) for a finenebulisation. For reference, a human hair has a diameter of 70 microns. These nozzles enable a high lung dose with nearmono-disperse inhalable droplets. Medspray can tune the devices and the nozzles to deliver aerosol to the larger airwaysor systemically through the alveolar region.Medspray is ISO 13485 certified for development and manufacturing of medical devices. The production of spray nozzles islocated at Medspray in Enschede, in dedicated ISO 7 clean rooms. World-wide partners assemble Medspray’s nozzles inmutually developed spray devices.Medspray’s mission statement is based on sustainability: Tiny technology for a sustainable future. The use of propellantsand other volatile organic components in spray cans for cosmetics and in inhalers can be completely avoided by usingMedspray nozzles and simple mechanisms like a plastic pump or a spring based syringe driver. Current HFA pMDIs(pressurized metered dose inhalers for e.g. Asthma and COPD) have a similar CO2 exhaust as a car trip of 290 km!






Organiser Sponsor

Wilber de Kruijf

Medspray Pharma BV, The Netherlands

Development of a soft mist inhaler using simulation tools to

predict lung dose and pharmacokinetics

Short CVFederica has a degree in Pharmacy obtained from the Federal Institute of Technology in Zurich(CH) obtained in 1996. She continued her studies at the London School of Hygiene and TropicalMedicine (UK) where she obtained a MSc in Control of Infectious Diseases, which led to herPhD on malaria research (Promoter analysis and molecular characterisation of glutathione S-transferases from the malaria mosquito Anopheles gambiae) obtained from Cardiff University(UK). She worked as a post-doctoral researcher first in Liverpool and London then in Perugia(IT) on projects studying the malaria mosquito immune system and malaria vaccinedevelopments on mice as well as research project administration for the whole research group.After several years as a post-doc Federica pursued a career in EU project management first atErnst and Young, then at European SchoolNet and finally at the COST Association where shehas been working since 2014.

Abstract The presentation will vert on how COST works, how can the research community profit fromCOST Actions and how to take part in COST. As an example, a brief overview of MP1404 -Simulation and pharmaceutical technologies for advanced patient-tailored inhaled medicines(SimInhale), will also be given.






Organiser Sponsor

Dr. Federica Ortelli

COST Office

An overview of the COST Programme

Short CVAlessandra Rossi graduated in Chemistry at the University of Pavia (Italy). She spent 6 months as ResearchFellow at the University of Gent (Gent, Belgium) and from 1994-1998 she did her PHD at University ofStrathclyde (Glasgow, U.K.) in the Department of Pure and Applied Chemistry and in the 1998 she had aPostdoc Research Fellowship from Novartis at Heriot-Watt University (Edimburgh, U.K.).She is Assistant Professor at the Food and Drug Department, University of Parma and DepartmentalCoordinator for the International Mobility. In 2010 and 2011 she was Invited Professor at University of ClaudeBernard Lyon1 (France), Faculty of Pharmacy.She is Management Committee Member of COST Project MP1404 “Simulation and pharmaceuticaltechnologies for advanced patient-tailored inhaled medicines (SimInhale)” and Leader of Working Group 1“Particle engineering/processing of inhaled medicines for local/systemic action”.The research interests are mainly focused on pulmonary delivery, in particular in the development of drypowder formulations and testing of nebulizers, and on oral delivery of swellable matrices for drug deliverycontrol, fixed dose combination products and multiparticulate systems.She collaborates with several international institutions and pharmaceutical companies in the development ofmedicinal products. She is author of more than 50 peer scientific papers on international peer journal, 4patents, 4 book chapters and several oral and poster communications to international congress.

Abstract This presentation is focused on the activities of the Working Group 1 during the four-years duration of theCOST SimInhale Action.The activities of WG1 have been addressed to the achievement of the objectives, such as:• identify optimal deposition sites for topical and systemic therapies;• consolidate information on the effects of lung disease on the deposition-dissolution-absorption pathway;• asses the effect of airway geometrical differences on regional deposition patterns;• promote deeper understanding of dissolution and absorption in the alveolar region;• assess emerging nanomedicine and excipient technologies in terms of efficiency and safety;• critical review of excipient choices in lung delivery and for the development of a library of powders with

differing properties through the choice of new excipients.






Organiser Sponsor

Prof. Alessandra Rossi

University of Parma, Italy

WG1 Presentation: Particle engineering/processing of inhaled

medicines for local/systemic action





1 October Speakers

Organiser Sponsor


Dr. Pantelis KoullapisUniversity of Cyprus

Cyprus

Nicolas SchwenckPARI

Germany

Dr. Fotos StylianouUniversity of Cyprus

Cyprus

Dr. Kyrre ThalbergAstraZeneca Gothenburg

Sweden

Dr. Frantisek LizalBrno University of

TechnologyCzech Republic

Prof. Martin SommerfeldOtto-von-Guericke University

Germany

Prof. Josue SznitmanTechnion

Israel

Prof. Per WollmerLund University

Sweden

Short CVPantelis Koullapis holds a Diploma of Mechanical Engineer from National Technical University of Athens(2013). He joined the Computational Sciences Laboratory (UCY-CompSci) of the University of Cyprus in 2013as a PhD candidate working on the prediction of airflow and aerosol deposition in the human airways usingcomputational methods. He was awarded a PhD from the University of Cyprus in 2018. The primary researchactivity of Pantelis is the use of high fidelity computer simulations for the prediction of drug deposition in theairways, in particular the prediction of regional deposition for various combinations of inhaler devices,patient groups (based on age or health status) and formulations. In this regard, he is interested in thedevelopment of In Silico In Vivo Correlations (ISIVCV) for deposition. Pantelis is pursuing the development ofhybrid models coupling the upper airways to the alveolar region, e.g. using LES methods for the upperairways with reduced models for the deeper lung generations. Pantelis’s research interests also include highfidelity simulations of inhaler devices. He has been involved in several research projects funded by companiesand academia.

Abstract Knowledge of deposition characteristics in the human airways is important when assessing the impact ofinhaled aerosols. Not only total, but also site-specific deposited dose within individual parts of the lung is ofinterest. The application of computer models that are based on computational fluid-particle dynamics (CFPD)for the prediction of aerosol deposition in the human airways has become very common nowadays. Despitetheir limitations, that are mainly associated to their high computational cost, CFPD models offer significantadvantages over in vitro / in vivo experiments. However, prior their use CFPD models needs to be properlyvalidated. The SimInhale benchmark case serves as a validation test case of computational tools intended forregional deposition studies in the upper airways. Within the activities of SimInhale, airflow and depositionmeasurements using Particle Image Velocimetry and positron emission tomography (PET) have beenconducted in a human-based model of the upper airways during steady-state inhalation at flow rates of 15,30 and 60 L/min. Large Eddy (LES) and Reynolds-Averaged Navier-Stokes (RANS) simulations were carried outin the same geometry and spherical particles were tracked to determine regional deposition patterns. CFDresults are compared against the measured data and best practice advice for accurate numerical predictionsis given.






Organiser Sponsor

Dr. Pantelis Koullapis


Predicting deposition in the human airways using CFPD:

The SimInhale benchmark case

Short CVDr. Lizal works as assistant professor at Department of Thermodynamics and EnvironmentalEngineering, Faculty of Mechanical Engineering, Brno University of Technology. He acquired his PhD in2012 for a thesis „Experimental Research of Aerosol Transport and Deposition in a Human RespiratoryTract“. His main research interest is in experimental modelling of human airways. Together with histeam he developed several replicas of human airways. He is interested in the influence of variousdiseases on the deposition of particles in human airways and experimentally investigates the flow offibers in human lungs. He is a member of the Czech aerosol society and the International Society forAerosols in Medicine.

Abstract Computer simulations will undoubtedly bring deeper insight into the mechanisms important for theinhaled aerosol therapy. However, validation of computational codes and their results is still an utterlynecessary step on the way to trustworthy numerical modelling. This talk introduces the availablemethods for the measurement of respiratory airflow and deposition of inhaled particles, both in vivoand in replicas of airways. Four categories of methods will be introduced: 1) point-wise and planarmethods for velocimetry in the airways, 2) classic methods for the measurement of the regionaldistribution of inhaled particles, 3) standard medical imaging methods applicable to the measurementof the regional aerosol distribution and 4) emerging and nonconventional methods. Each of thepresented experimental methods has its limitations and advantages, these will be discussed andevaluated.






Organiser Sponsor

Dr. Frantisek Lizal

Brno University of Technology, Czech Republic

Experimental methods applicable in research of flow and

aerosol deposition in human airways and their replicas

Short CV• PARI Group

• Portfolio Manager eFlow Partnering, since 2019• Strategic Marketing Medical Devices, 2019• Technology Platform Leader Aerosol Physics, PARI GmbH, 2015 - 2018

• German University of Cairo, Berlin Campus• Lecturer: Numerics and Finite Elements, 2016 -2018

• University of Stuttgart• Lecturer: Fluid Mechanics and Advanced Fluid Mechanics, 2015• PhD: Numerics and Software Development in Fluid Mechanics, 2010 - 2014• Diploma: Aerospace Engineering, 2010

Abstract PARI’s mission is to improve the lives of those affected by respiratory diseases and those who provide care tothem. This is reflected in our comprehensive portfolio of innovative products and services. In the spirit of thismission, some in-vitro experiments for early stage development phases of novel nebulizer systems tocharacterize aerosol and its deposition to the human lungs, are presented.






Organiser Sponsor

Nicolas Schwenck

PARI, Germany

Aerosol characterization for the development of novel

inhalation devices: in-vitro experiments

Short CVProf. Martin Sommerfeld studied Aeronautical Engineering (Diploma 1981) and completed his Doctoral degree (1984)at the Technical University Aachen (RWTH). Since January 2017 he is a Professor at the Otto-von-Guericke UniversityMagdeburg (OvGU) Faculty Process and Systems Technology, Working group Multiphase Flow Systems. His researchactivities are mainly concentrated on fundamentals of dispersed multi-phase flows with the aim of developing physicalmodels for describing relevant transport phenomena. For the analysis of multi-phase flow transport phenomenadetailed experiments using modern optical instrumentation as well as direct numerical simulations (e.g. by the Lattice-Boltzmann-Method) are performed. The developed advanced models are used in the frame of the Euler/Lagrangecomputational approach (implementation in OpenFOAM) for allowing the prediction of industrial scale processesinvolving dispersed multi-phase flows. His is the Coordinator of the ERCOFTAC special interest groups “DispersedTurbulent Two-Phase Flows” and Chair of the ProcessNet special topic group “Computational Fluid Dynamics”.

Abstract Recently the state-of-the-art in numerically simulating dry powder inhaler (DPI) performance by CFD methods wasreviewed by Sommerfeld et al. (2019). The formulations used in DPI are either blended large carrier particles oragglomerated fine drug powders. Essential for a good performance and hence a high fraction of fine particle releasefrom the DPI are detachment of fine drugs from carriers or aerosolisation of agglomerates due to flow stresses andwall impacts as well as prevention of drug particle deposition on the inhaler walls. Here numerical simulationsconducted over recent years on different scales are summarised which highlight the mechanisms influencing theefficiency of fine particle emission from inhalers:• Computation of the swirling flow field through a Cyclohaler based on RANS with the k-ω-SST turbulence model and

Lagrangian carrier particle tracking for the determination of statistics on flow stresses acting on carrier particles aswell as carrier-wall collision statistics. Based on experimental information for adhesion properties, flowdetachment probabilities were determined.

• The recorded fluid stresses (relative velocity, turbulence and shear stresses) acting on the carrier were used toperform fully resolved Lattice-Boltzmann simulations (e.g. 110 μm carrier with 882 drug particles of 5 μm). Theresults showed that flow detachment is of minor importance and may only happen through sliding or rolling.Turbulence in addition may remarkably enhance drug particle lift-off.

• In order to allow the determination of drug particle detachment from carriers upon wall collisions a novel inertia-based model was derived in the frame of the discrete particle method (DPM). Euler/Lagrange simulations of aCyclohaler and a Unihaler applying this model revealed that almost 100 % of the drugs were detached through thenumerous wall impacts.

• The possibility of fine drug particle wall deposition was studies using Euler/Lagrange computations combined withan energy-based wall deposition model. Depending on the wall collision parameters (controlled by particle andwall material) and type of inhaler device quite a considerable fraction of drug particles are deposited.






Organiser Sponsor

Prof. Martin Sommerfeld

Otto-von-Guericke-University Magdeburg, Germany

Dry Powder Inhaler Performance: A CFD-Euler/Lagrange study

Short CVFotos Stylianou holds BSc and MSc degrees in Physics from the University of Cyprus. He received his PhDdegree in Mechanical and Manufacturing Engineering from the University of Cyprus in 2016. During hisundergraduate studies he was awarded several times for his performance in the core courses of Physicsdegree. At the beginning of his postgraduate studies, he received a PhD Scholarship from the Cyprus StateScholarship Foundation. Since 2010 he has been an active member at the Computational Sciences Laboratory(UCY-CompSci), and from 2015 he has joined the COST action “Simulation and pharmaceutical technologies foradvanced patient-tailored inhaled medicines” (SimInhale). He has been involved in research projects funded bythe following Pharmaceutical Companies: Elpen Pharmaceutical Co. Inc., Mylan Pharma UK Ltd, PureIMSPharmaceuticals, and Aptar Pharma. He has also been involved in research projects funded by the CyprusResearch Promotion Foundation, and the US Army International Technology Center and the US Air ForceEuropean Office of Aerospace Research and Development His main research interests are on the reduction ofextrathoracic drug losses of inhaled medications, and on the optimization of Dry Powder Inhalers. Recently, hehas been working on the deposition uniformity of saline water droplets in the extrathoracic airways duringbreathing from nebulizer-like moisturizing systems. He is also interested in the development of Structure-Based turbulence models with improved predictive capabilities suitable for biomedical fluid flows.

Abstract In this talk we review some of the work performed by the UCY-CompSci Lab and our collaborators (EmmaceConsulting AB, PureIMS, Institute of Chemical Process Fundamentals of the ASCR) during the SimInhale COSTaction. We begin with a short reference to our early CFD work on particle laden flow through a single airwaybifurcation model. We proceed with a combined in silico and in vitro study in an MRI-based mouth-throat-trachea geometry. We analyze the effect of flow rate, head position, and inhaler orientation on the airflow andparticle deposition fractions/sites. We continue with flow visualizations and particle tracks in a DPI-inhaler. Forthis case study we highlight important insights gained from CFD, even without accounting for the completeairflow-particle interplay. We proceed with an in vitro and in silico study in a bent pipe geometry. For this casestudy the hygroscopic growth of sub-micrometer NaCl particles is examined under normal body and inhalationconditions. We conclude by extending the previous work to a CT-based human airway tree geometry andevaluate the delivery efficiency of drug-excipient hygroscopic composites.






Organiser Sponsor

Dr. Fotos Stylianou


Understanding inhaled drug delivery using in silico and in vitro methods: Case studies involving inhaler and simplified

or realistic human airway geometries.

Short CVJosué Sznitman is a Swiss, French and Israeli national. Born in France, he grew up in the US beforemoving to Switzerland. Sznitman graduated from MIT with a BSc in Mechanical Engineering (2002),followed by a Dr. Sc. (2008) from the ETH Zurich. Following postdoc training at UPenn and PrincetonUniversity, he joined the Department of Biomedical Engineering at the Technion in 2010 as a tenure-track Assistant Professor and was promoted to Associate Professor with tenure in 2016. Josué’sresearch focuses on respiratory flow phenomena and drug delivery to the lungs. He was awarded theYoung Investigator Award (2015) by ISAM for a researcher under 40 and most recently the 2018Emerging Scientist Award in Drug Delivery to the Lungs (The Aerosol Society, UK).

Abstract Lung-on-chips provide new opportunities to probe at true scale the pulmonary environment anddeliver biomimetic platforms. Microfluidic airways have transformed the landscape for exploring invitro respiratory physiology and advance basic research and translational medicine. Since drugscreening methods are still overwhelmingly conducted in animal models, lung-on-chips offer theprospect of tangible alternatives. Lined with human cells, within a physiologically-faithful architecture,these can help reduce the need for animal studies and offer more relevant human models. We areleading major developments in lung-on-chips, with the first artificially-breathing acinar networks thatcapture physiologically-realistic respiratory flows. Our acinus-on-chip represents the first in vitro toolenabling quantitative monitoring of inhaled aerosols at the acinar scales. The life-size model lungallows direct and time-resolved observations of airborne particle trajectories and deposition patterns.We are expanding such platforms to recapitulate biological barrier functions of the airway epitheliumfollowing inhalation exposure, including pathogenic aggression. Airway cells can be collected frombiopsy and cultured in devices allowing for advanced diagnostics in addition to monitoring patient’scell response to different drugs. Our models may provide off-the-shelf kits geared to end-users for awide range of toxicity assays and drug screens.






Organiser Sponsor

Prof. Josue Sznitman

Technion, Israel

Advanced in vitro lung-on-chip platforms for inhalation

screening assays

Short CVDr. Thalberg is Associate Principal Scientist at AstraZeneca Gothenburg. He obtained a Master degree inChemical Engineering (1981) from Lund University, Sweden, and a Ph. D. in Physical Chemistry from the sameuniversity (1990) on the topic of polymer – surfactant interactions in aqueous solutions.Since 1991, Kyrre has been working with AstraZeneca, first at the site in Lund originally called Draco, now inMölndal, both Sweden. During this time, Kyrre held a number of positions and provided key contributions toseveral inhalation products on the market, in particular the Turbuhaler® dry powder inhalers. The currentposition as Associate Principal Scientist has a focus on fundamental understanding, application and scale upof dry powder formulations. Kyrre has authored or co-authored more than 30 publications in internationaljournals and is an inventor on a couple of patents.Aside from inhalation science, Kyrre Thalberg writes children’s books about Kjetil the dragon and little PrincePralin together with his partner.

Abstract This work aims to develop a fundamental and integral simulation model for dose emptying from a dry powderinhaler. A main challenge is that the inhalable drug particles are too many to be tracked in the simulation. Toresolve this, fine drug particles are studied in micro-scale simulations, which are subsequently combined withmacro-scale simulations of powder emptying from the device. In this way, the simulation model is able todescribe powder emptying, drug dispersion and drug retention, which are key characteristics of the dosefrom a dry powder inhaler.To validate the simulation tool, two different adhesive mixture formulations were prepared and analyzed intwo very different inhaler geometries using the Next Generation Impactor, NGI. Fine particle fractionsobtained ranged from 20 to 70%. The main challenge as regard the modelling is to identify the adequateparticle interaction parameter. Surface energy data obtained from inverse gas chromatography were notuseful in this respect. We instead adopted an “apparent surface energy”, ASE, approach. By applying an ASEdistribution to each of the formulations, good correlations between simulated and experimental data couldbe obtained. Current work aims to expand the multi-scale simulation tool to be able to deal with formulationsconsisting of fine particles only.






Organiser Sponsor

Dr. Kyrre Thalberg

AstraZeneca Gothenburg, Sweden

CFD – DEM simulations of dry powder inhalers

Bridging to reality

Short CVPer Wollmer is professor of Clinical Physiology and Nuclear Medicine at Lund University since 1992. Heis also honorary consultant in Clinical Physiology at Skåne University Hospital, Malmö. ProfessorWollmer’s main research interest is in pulmonary pathophysiology. He has worked extensively withdevelopment of new methods for studying pulmonary pathophysiology. Another field of interest isdeposition of inhaled aerosols. Professor Wollmer has published more than 300 papers ininternational, peer-reviewed journals and supervised more than 20 PhD students.

Abstract Inhaled nanoparticles penetrate readily to the distal air spaces, where they are largely depositeddiffusion. The probability of deposition of a nanoparticle of a given size therefore depends largely onthe residence time of the particle in the lung and the distance to an airspace wall. We have shown thatit is possible to calculate the dimensions of distal airspaces from a short series of aerosol inhalationsfollowed by breath-hold of 5-10 s and measurement of the particle concentration in exhaled aerosoland in an alveolar sample of exhaled gas. At a volumetric lung depth of 1300 mL, the radius of thedistal airspaces measured by this method is approx. 0.3 mm in healthy subjects. In subjects withchronic obstructive pulmonary disease, the dimensions are larger. We find good correlation betweenthe distal airspace dimensions and the extent of emphysema as measured by computed tomography.Measurement of distal airspace dimensions thus shows promise as a diagnostic technique fordetection of emphysema. The method for measurement of the deposition of nanoparticles in singlebreaths may also be useful in pharmaceutical research.

Per Wollmer, Jonas Jakobsson, Laura Aaltonen, Jakob LöndahlDepts. of Translational Medicine and Ergonomics and Aerosol Sciences, Lund University, Sweden





Prof. MD. Per Wollmer

Lund University, Sweden

Measurement of pulmonary deposition of nanoparticles as a

means for morphometry of the distal air spaces and

diagnosis of emphysema


Organiser Sponsor





2 October Speakers

Organiser Sponsor


Prof. Maria CordinaUniversity of Malta

Malta

Dr. Antonios LalasCentre for Research and Technology Hellas

Greece

Dr. Aditya DasPharmaceutical Consulting LLC

USA

Dr. Carsten EhrhardtTrinity College Dublin

Ireland

Short CVProf Maria Cordina graduated in Pharmacy from the University of Malta in 1992. She was awarded a scholarship to read for a PhD at Queen'sUniversity of Belfast, NI and graduated 1998. Her research focused on pharmaceutical care of asthma patients. She additionally holds adiploma in Health Outcomes Research. She has published extensively in the fields related to therapeutic management of respiratory disease,professional practice, delivery of pharmaceutical care, medicines use incorporating also gender issues. She has been a guest speaker atnumerous national and international conferences in addition to organizing and chairing multiple conferences.Prof Cordina is extensively involved in research. She has participated in a number of international multi-center studies, has cooperated withvarious institutions and has cooperated with various institutions and has a keen interest in inter-professional collaboration. In addition tosupervising students at the University of Malta, she has supervised/co-supervised various In recognition of her contribution toPharmaceutical Care Network Europe(PCNE)and the development of Pharmaceutical Care she was awarded honorary life membership toPCNE.Prof Cordina founded the Malta College of Pharmacy Practice in 1996 was also the editor of the Journal of the Malta College of PharmacyPractice for many years. She acts as expert elevator for the European Commission's research framework programme (DG Research). Aso sheacts as temporary adviser to WHO in relation to pharmaceutical matters and education for the region of the Newly Independent States,mainly the Central Asian Republics of Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan additionally to Moldova, Armenia and the RussianFederation. She has been appointed Head, WHO Collaboration Center for Health Professionals Education and Research following thedesignation of the department as a WHO Collaborating Center in 2018.

Abstract Inhaled therapy in the cornerstone of medication management in a number of chronic conditions including, but not limited to, asthma andCOPD. The World Health Organisation puts the prevalence of asthma 235 million at and that of COPD at 65 million. Data shows that in 2015,2.3 million died from COPD and 0.4 million died of asthma. These conditions are contribute significantly to the burden of non-communicabledisease.Inhaled therapy, makes perfect pharmacological sense in the management of respiratory disease and has led to the development of aplethora of devices, each with a set instructions, that if followed correctly, should, in theory, in most cases, lead to positive patient outcomes.Yet as the data above demonstrates this is not the case.Studies demonstrate that about 28% of adult prescriptions to start inhaler therapy are not dispensed. We know that adherence to therapy(this has various meanings and interpretations) is about 50% and of those an average of these, 50% have poor inhaler technique. While theliterature is replete with effective interventions to address this issues, in real life scenarios, the situation is complex and the sustainedeffectiveness is not evident.Producing an inhalation device involves researches from a number of highly specialised scientific non-clinical fields. It is imperative that theseresearchers are cognisant of the needs and issues that are faced by patients from the inception of the research process in order to explore,study and design products, that in addition to having the advantages described earlier, are the least intrusive, have high patient acceptability,and pose the least possible burden on the individual. Once the product is in its final stages or already on the market, it is possibly too late toovercome barriers posed by the device, as healthcare providers can only work with what is available, thereby limiting their success.It is imperative for the latter researchers to take into account not only pathophysiological issues, but the social and emotional aspects of thediseases, when delivering products to manage respiratory conditions. In working towards achieving universal health coverage in line with theUN sustainable development goals, we should strive to address these issues to ensure that no one is left behind, and as things stand, patientswho use inhaled therapy are being left behind in plain sight.






Organiser Sponsor

Prof. Maria Cordina

University of Malta

'Trying but failing': medication delivery via inhalers-

Let's leave no one behind

Short CVDr. Antonios Lalas is a postdoctoral research associate in Centre for Research and Technology Hellas / InformationTechnologies Institute (CERTH/ITI). He received the Diploma and Ph.D. degrees from the Department of Electrical andComputer Engineering, Aristotle University of Thessaloniki (AUTH), Thessaloniki, Greece, in 2006 and 2012, respectively.During the period 2012-2018, he has served as an adjunct lecturer at the Department of Informatics and TelecommunicationsEngineering, University of Western Macedonia. He has also served as postdoctoral research fellow at the Department ofElectrical and Computer Engineering, AUTH, during the period 2013-2015. His research interests include artificial intelligence,acoustic detection applications, computational fluid dynamics, particle tracing, computational electromagnetics, visualizationof physical information, Blochchain technology and IoT in relation to the eHealth domain, as well as cyber-security for medicaldevices. These involved the recognition of lung sounds for smart inhaler applications, the assessment of particles influenceinto human lungs during asthma exacerbations and various environmental conditions, as well as wireless power transfer basedon metamaterial technology and its interference with humans. In addition, his research interests include sensors and RFcircuits design, radio frequency microelectromechanical systems (RF-MEMS), and THz technology in medical applications. Hehas authored sixteen (16) papers in international scientific peer review journals and more than thirty six (36) papers ininternational conferences and events. He has also been involved in several research projects, such as myAirCoach, BADGER,AVENUE, ALADDIN, ACMIMS funded by the European Commission and the Greek secretariat of Research and Technology.

Abstract The Take-A-Breath project envisions an innovative system of personalized monitoring and self-management of respiratorydiseases (COPD, asthma), that takes into account cutting-edge clinical research and the emergence of new bio-indicators, withinnovative Information and Communication Technologies (ICT). The project aims to raise awareness to patients regarding theclinical implications of their status, to monitor their adherence to treatment and medication plan, as well as to significantlyincrease the effectiveness of the medical care. Additionally, the project focuses on the clinical research of new biomarkersassociated with respiratory diseases by examining a wide range of behavioral, environmental, and psychosocial parameters.Finally, the project adopts and develops an ambitious and innovative approach to monitoring the use of inhaled respiratorymedicine, combined with training procedures, aiming on providing medical assistance and self-improvement. Thus, a wirelesspersonal add-on system in the form of a bio-network has been developed using sensors and technologies capable of adaptingto any drug inhalation device (pMDIs, DPIs), in order to eliminate "critical errors", to consider important behavioral andenvironmental parameters of the patients, and to send useful data to a local processing system of medical inference. Thesystem is accompanied by a personalized monitoring, guidance and patient’s training platform on a mobile device (phone/tablet) that can be used as a platform for personalized guidance and support to prevent a possible exacerbation of a chronicrespiratory disease. The specialized mobile application allows the collection of all data in real time and handles the interactionwith the user as well as the personal guidance for the effective education of the patient. The add-on works with the audiosignal processing system to draw conclusions about the use of the equipment but also about the patient's technique. Thepatient is trained by utilizing the camera of the mobile device, in order to recognize the correct use of inhalation devices andin issuing corrective instructions and interactive reports. Guidelines are provided to patients through augmented realitytechniques and gamification mechanisms, as well as a virtual assistant. Appropriate interventions, such as medical assistancefrom a doctor, or self-management of exacerbations, are proposed.






Organiser Sponsor

Dr. Antonios Lalas

Information Technologies Institute, Centre for Research and Technology Hellas

(CERTH), Greece

Intelligent Clinical Platform for Self-management, Training,

and Support of Chronic Respiratory Patients

Short CVAditya Das is a Director of Business Development at Recipharm AB focused on Inhalation Drug ProductDevelopment and Commercialization for global Clients. As a Business Development professional serving thepharmaceutical industry, Dr. Das coordinates the interface between client needs and externalservices/capabilities to facilitate strategic positioning for optimal product development and globalregistration. Services provided to clients in response to specific requests include regulatory input (chemistry,manufacturing and control sections), risk analysis, cost estimates, process design, and combination(drug/device) product development for both small and macromolecules. Dr. Das' due diligence activitiesinclude technology evaluation/out-licensing and in-licensing for combination products, for mergers andacquisitions and for a specific strategic joint venture opportunity in India related to contract manufacturingand research services, involving a survey and audit of 12 companies. He has been involved in combinationbiopharmaceutical product development for more than 25 years related to parenteral (pulmonary,transdermal, intravenous and implanted) and oral drug delivery therapeutic strategies. Dr. Das has authoredand coordinated the filing of 29 IND's for both small and macromolecules and assisted with the successfulfiling of 3 CTD/NDA’s (for Dry Powder Inhaled Insulin, "Exubera®", approved by the FDA and EMA in Jan 2006;Thermal Aerosol Vapor Generated Staccato Loxapine, “Adasuve®” approved Dec 2012 and Dry PowderInhaled Tobramycin, “Tobi Podhaler®” approved March 2013). These efforts were directed to both single drugand combination products used for the treatment of infectious, allergic, genetic and neurological diseases. Heis an Inventor on 8 issued Patents covering thiocationic lipids for gene delivery, a taste masked Ibuprofensuckable tablet and spray dried formulations for nasal and inhaled drug delivery. Dr. Das earned his Ph.D.degree in Chemical Engineering studying the effects of inhaled inorganic dusts and their role in the etiology ofsilicosis at a joint program between West Virginia University and the National Institutes for OccupationalSafety and Health and an MBA (Strategy) from the University of California at Irvine where he was a recipientof an Outstanding Service Award for his activities in support of the Graduate School of Management, UCI. Healso earned an MS degree in Chemical Engineering from Carnegie Mellon University supported by a MellonFellowship and a BS degree in Chemical Engineering from the University of New Hampshire supported byScholarships from the International Students Office and a Fellowship from the Winchester R. Wood MemorialFoundation.






Organiser Sponsor

Dr. Aditya Das

Pharmaceutical Consulting LLC, USA

Inhaled drug product development and commercialization

Short CVCarsten Ehrhardt is Professor in Pharmaceutics and Biopharmaceutics at the School of Pharmacy andPharmaceutical Sciences, Trinity College Dublin. In addition, he is holding an Adjunct Professorship at theSchool of Pharmacy, University of Southern California. He was elected Fellow of Trinity College Dublin in2013. Carsten obtained his Ph.D. in Biopharmaceutics from Saarland University in 2003. His research isfocused on lung drug disposition, pulmonary epithelial transport and molecular origins of airways disease. Hehas edited 1 book and (co-)authored 91 peer-reviewed publications and more than 230 abstracts andconference proceedings. Carsten has given over 120 invited oral presentations. He is the proud recipient ofhonours and awards from DPhG, APS and Galenus Foundation. Carsten actively serves on the Editorial Boardsof the American Journal of Physiology - Lung Cellular and Molecular Physiology, European Journal ofPharmaceutics and Biopharmaceutics, European Journal of Pharmaceuticals Sciences, Journal of AerosolMedicine and Pulmonary Drug Delivery and Journal of Pharmaceutical Sciences.

Abstract Virtually every cell in the body is equipped with a tightly regulated machinery of membrane transporterproteins. These transporters facilitate cellular entry or efflux of their substrates across lipid bilayermembranes. Efflux transporters, which often require primary or secondary metabolic energy to function,have important physiological roles in maintaining barrier function and cellular detoxification and clearance. Inthe context of drug delivery, however, the protective function of efflux transporters sometimes negativelyimpacts on bioavailability, in cases where the drug in question is a substrate for such transporters. This canlead to reduced gastrointestinal absorption, increased hepatic and/or renal clearance and restricted access tocertain compartments, such as the brain. Moreover, upregulated transporter expression in cancer cells canresult in resistance of tumours to chemotherapy.Whilst a wealth of information has been published on transporter effects in drug disposition in the gut, liver,kidneys and the blood-brain-barrier, pulmonary transporter research remains a relatively poorly understoodarea of research. This presentation will discuss the expression of relevant members ATP-binding cassette(ABC) transporter family, namely, P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) andbreast cancer resistance protein (BCRP) in the lung and in addition, will highlight the clinical impact theseefflux transporters can have on pulmonary cell function, detoxification and drug disposition.






Organiser Sponsor

Dr. Carsten Ehrhardt

Trinity College Dublin, Ireland

Efflux transporters in the lung





Short Term Scientific Mission STSM Presentations

Organiser Sponsor


Snezana RadivojevMedical University of Graz

Austria

Prof. Marco Agostino DeriuPolitecnico di Torino

Italy

Short CVMs. Snezana Radivojev is currently working on her PhD thesis in a cooperation between RCPE (Research CenterPharmaceutical Engineering) and the Medical University of Graz in Austria. Her PhD research is focused on theestablishment of in-vitro-in-vivo correlation through the development of new/improved in-vitro and in-silicomethodologies, following the rational understanding of orally inhaled product’s biopharmaceutics. Sheacquired her MSc degree in Chemical and Pharmaceutical Engineering from Graz University of Technology in2017 and started her carreer in RCPE as a scientist in the inhalation group. Her BSc diploma in Chemistry isfrom University of Novi Sad, Serbia. Aside from her research, she is interested in actively promotingnetworking opportunities between PhD students coming from different backgrounds of knowledge anduniversities in the field of inhalation.

Abstract Presently, pharmacopeial methods for the assessment of the in-vitro performance of orally inhaled products(OIPs) are exclusively focused on the aerodynamic particle size analysis and dose uniformity. However, it hasbeen recognized that even though these methods are suitable for quality control, they are over simplisticwhen replicating the in-vivo behavior. In the last few years, the value of applying in-silico approaches tofacilitate the development of new medicinal products have been widely recognized. Nevertheless, thedevelopment of reliable in-silico models for inhalation is presently a challenge due to the lack of knowledgethat still exists about the fate of drugs in the lung as well as the absence of more robust predictivestandardized in-vitro methodologies. Consequently, by using new methodologies in the field of OIPsdissolution, this study aimed to evaluate the potential development and applicability of an in-vitro-in silicoapproach as a risk-assessment tool for the life cycle of dry powder inhalers (DPIs). The presentation will coverthe cooperation work between RCPE (Research Center Pharmaceutical Engineering) and King’s College, underthe umbrella of the SimInhale COST action. The challenges to be faced during the development of new in-vitroand in-silico methodologies as well as their potential solutions will also be discussed.






Organiser Sponsor

Snezana Radivojev, Research Center Pharmaceutical

Engineering, Medical University of Graz, Austria

STSM oral presentation

DPI mishandling: Influence on in-vitro drug deposition,

dissolution and pharmacokinetics

Short CVMarco A. Deriu is Professor of Industrial Bioengineering at Politecnico di Torino. He has received the EuropeanDoctorate in Biomedical Engineering in 2009 at Politecnico di Torino, Italy. His research is focused oncomputational modelling and data analysis applied to investigate mechanisms behind biological, physiologicaland pathological functions. In this context, he employs multiscale modelling to investigate molecularmechanisms of cancer and neurodegenerative diseases, drug mechanism of action, drug delivery systems,protein folding, nanoparticle features and biophysical properties. Part of his research is also devoted to thedevelopment of modelling methodologies to interpret and treat biophysical, biological and clinical data, tobuild prediction models in physiology and physiopathology. He teaches “Multiscale Modelliing inBiomechanics”, “Biomechanical Design”, and “Rational Drug Design: Principles and Applications” at Politecnicodi Torino. He is author of several publications in International peer-reviewed Journals, book chapters andproceedings in the field of computational modelling applied to Bioengineering, Biophysics, Molecular Biologyand Medicine.

Abstract Hyperbranched polymeric (HP) nanoparticles emerged as a new class of structure with outstanding features for nanomedicine. Among them, dendrimers are unique tree-like branched polymers with biomolecules-like properties, low polydispersity and high degree of versatility. In recent years, HP nanoparticles have been extensively studied for their potential application as delivery systems and therapeutic agents targeting several pathological conditions. Properties of the above mentioned nanoparticles directly depend on physicochemical, molecular and supramolecular characteristics. However, the assessment of these aspects often requires expensive experiments, spatial and temporal resolution at the nanoscale, barely obtained by in vitro analysis. In this context, computational molecular modelling has widely demonstrated to be a powerful strategy to characterize nanoparticle physical-chemical properties and mechanism of action. This talk deals with the use of computational modelling to investigate molecular characteristics of hyperbranched polymers for diagnostic/therapeutic applications, such as dendrimers for siRNA delivery, targeting the Chronic Obstructive Pulmonary Disease. Here, molecular and multiscale modelling allow to characterize how particle functionalization drives the polymer chemical and physical properties toward a different ability to bind siRNA.






Organiser Sponsor

Prof. Marco Agostino Deriu

Department of Mechanical and Aerospace Engineering (DIMEAS)Politecnico di Torino, Italy

STSM oral presentation

Molecular Modelling to Design/Characterize Hyperbranched Polymer

Nanoparticles Employed as Delivery Systems or Therapeutic Agents in

Nanomedicine

Documents

Conference Program · Bacteriophages and endolysins to tackle respiratory infections caused by superbugs COST is supported by the EU Framework Programme Horizon 2020 Organiser Sponsor