Annual
Scientific Report
2012 | 2013
A nn ua l Scientific Repor t 2012 | 2013Research Center Pharmaceutical Engineering GmbH
Inffeldgasse 13
8010 Graz, Austria
Telephone: +43 316 873 30901
Telefax: +43 316 873 30902
E-Mail: [email protected]
Published by: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, A-8010 Graz Printed by: MWW Medien GmbH, Sperberhorst 6, D-22459 Hamburg (www.mww-online.de) Design & Typesetting: Benjamin Augustin, Kienitzer Str. 114, D-12049 Berlin (www.benjaminaugustin.com)
Photos: RCPE GmbH, Lichtmeister Photography, SFG, FFG/Spiola, Harry Schiffer, Fotoatelier Moser, Foto Furgler, iStock by Getty Images
Research Center Pharmaceutical Engineering GmbH Managing Director: Mag. DI Dr. Thomas K. KLEIN Scientific Director: Univ.-Prof. DI Dr. Johannes G. KHINAST Inffeldgasse 13 8010 Graz, Austria Telephone: +43 316 873 30901 Telefax: +43 316 873 30902 E-Mail: [email protected] Internet: http://www.rcpe.at Legal Reg: FN 312899x, LGZRS Graz VAT (UID): ATU64272307
Funding Institutions:
within the framework of the Austrian K1 – Program:
Austrian Research Promotion Agency (FFG), Structural Programs
Styrian provincial government (Land Steiermark) – Dept. for Science and Research Styrian Business Promotion Agency (SFG)
Shareholders:
Graz University of Technology (65%) University Graz (20%)
JOANNEUM RESEARCH (15%) Share capital: € 100.000,–
Statement of the Directors 04
Vision, Mission and Goals 06
Highlights 2012/2013 08
Statements of RCPE’s Stakeholders 10
Organization and Management
14Structure 16
Human Resources and Diversity Management 20
Key Personnel 24
Key Researcher 26
Research
28Opportunities for Cooperation: Types of Research Projects 30 Presentation of selected Research Projects 32 Test Facilities and Simulation Tools 48
Scientific Output of the Centre
54Publications 56 Academic Theses 63 Patents 65 Workshops 66 Guest Lectures 66
Financial Annex
68 Bilanz 70Gewinn- und Verlustrechnung 72
Boards and Partners
74General Assembly 76
Supervisory Board / Strategy Board 76
Scientific Advisory Board (SAB) 76
Program Committee 77
Business Partners 78
Scientific Partners 82
Supporting Partners 84
Statement of the Directors
With regard to knowledge transfer, RCPE further strengthened its position in the international sci-entific community: 33 articles in peer-reviewed journals, 39 conference contributions, 14 pleted master and diploma theses, and 5 com-pleted dissertations attest to its outstanding sci-entific work.
Worldwide Network
In addition to advanced research, RCPE acquired several new industry and research partners (cur-rently over 90 in total) during the last fiscal year. The growing number of partners shows the steady demand for cooperating with RCPE and reflects on the Center’s outstanding research performance. In addition to the long-established cooperation with the Graz University of Technology, the Univer-sity of Graz, Joanneum Research and the Universi-ty of Applied Sciences Joanneum, in the last fiscal year the Medical University of Graz became the Center’s scientific partner, further securing RCPE’s scientific leadership.
Awards
In recognition of its success, RCPE received several awards last year, including the Best Poster Award at the Austrian Proteomic Research Symposium, the Best Presentation Award at the annual AIChE meeting in Pittsburgh (USA) for the paper “Cap-sule Filling Operations Using a Nozzle Dosator” and a STEP Award 2012 in the category “Product/ Technology.” Moreover, the only Austrian finalist in Frankfurt, RCPE secured the highly-acclaimed Business Award for Future Branches for the prov-ince of Styria with its revolutionary project “Pills on Paper” and received yet another proof of the international recognition of its work.
Spin-offs
In the last fiscal year RCPE confirmed that it offers innovative and marketable products that add value and create jobs. The Center had two new spin-offs in the year 2012/2013. The
Continuous Growth
In the fiscal year 2012/2013 RCPE strengthened national and international collaborations and achieved a record contract volume of over 2.5 million Euro since its foundation. Since 2008, over 50 national and international research projects have been completed. It is clear that the Center’s steady and viable growth is secured long-term due to RCPE’s innovation and sustainability strategy. It also applies to staff development, with regard to which another record was set: in the fiscal year 2012/2013, RCPE had on average 87 employees.
Successful Research Review
Participating in EU projects has significantly con-tributed to RCPE’s success. In the first half of 2013, the EU-FP7 project “IPROCOM” was launched with 10 research and technology partners from across Europe. The goal of IPROCOM is to meet scientific and technological challenges in the particulate products manufacturing via a coordi-nated and structured research training program. In addition to IPROCOM, RCPE won the project MediPrint within the framework of EUREKA Euro-stars, which also began in the first half of 2013 and whose goal is to develop a pharmaceutical print-ing system for a personalized therapy in oncology and pediatrics.
Two workshops held by RCPE for the first time in Graz were the highlights of the fiscal year 2012/2103. One was a high-profile international event of the International Association for Pharma-ceutical Technology (APV) on the topic of “Con-tinuous Manufacturing” at Graz University of Tech-nology in September of 2012. The other one took place in July of 2012 with high-level experts pre-senting “CFD for Dispersed Multiphase of Flows” in the Best Practice Guidance Series organized by the European Research Community on Flow, Turbulence and Combustion (ERCOFTAC) from Great Britain. Once again, RCPE proved to be an important link between industry and science and contributed to its international reputation.
Statement of the Directors
first one, roombiotic probiotic solutions, offers innovative technologies for removing dangerous contaminants and originates from the project “Innovative Concepts in Clean Room Technology” launched in 2009 at RCPE, which developed new strategies for cleanroom disinfection that were later implemented by roombiotic probiotic solutions. The second spin-off, SES-Tec (Scientific & Engineering Simulation Technology), provides innovative solutions to complex problems in multi-physics simulations and fills the existing gap in product and process optimization. Together with the spin-off PRSG, they bring the count of RCPE’s spin-offs to 3 during its 5-year existence and prove that science and industry can successfully coexist.
Prospects
In the fiscal year 2013/2014, RCPE will continue to follow the successful path of steady and moderate growth. The Center intends to refine its strategy for the upcoming new COMET funding period: together with the key researchers and partners, the Center’s management team is developing a future-oriented research program. Our research and industry partners welcome the new research
Univ.-Prof. DI Dr. Johannes G. Khinast
Scientific Director / Leader
Mag. DI Dr. Thomas K. Klein
Managing Director
program and recognize that developing drugs of the future has tremendous innovation potential. At the project level, our primary focus is on in-tensifying cooperation with our COMET partners and developing innovations to strengthen our business partners. With new research applications at the national and European levels, we plan to expand our scientific network and advance our re-search skills.
We are confident that our research efforts contrib-ute significantly to the development of drugs of the future and look forward to new challenges in the year 2013/2014.
We would like to thank our highly-motivated team, our partners, clients, and sponsors from industry, research and public sector for their cooperation. Their profound engagement has made innovation possible.
We look forward to the new fiscal year and to dis-covering new ideas that will help us to achieve our ambitious goals.
We make
tomorrow’s drugs
possible!
Vision
It is our aim to transform pharmaceutical product and process
development from an empirical approach to a rational and
science-based endeavour in accordance with ICH’s QbD
framework.
Mission
• Combination of multi-disciplinary knowledge for
science-based drug product and process development.
• Close collaboration with Austrian and international
partners to foster competitiveness and to strengthen our
partners’ economic success.
• Technology and innovation platform for science and
industry.
• Integration of targeted educational and
gender-mainstreaming activities to create tomorrow’s workforce.
• Raising public awareness of the importance of research
and science.
Goal
To be the national and European focal point for
science-based development of structured drug products and
diagnostics, as well as their manufacturing processes.
AUG 31
JUL 01
SEP 26
-SEP 27
DI Mag.
aDr.
inEva Littringer completes the first
disser-tation at RCPE (title: “Maßgeschneiderte
Trägerpar-tikel für Pulverinhalte”).
The second spin-off of RCPE, „roombiotic – probiotic
solutions“, is launched.
Massimo Bresciani becomes new Director of Scientific
Operations.
Simon Fraser and Simone Klein receive a general
power of attorney.
New group leaders: Marcos Llusa and Sharareh
Sal-ar-Behzadi take over the management of the
„Ma-terial Science“ and “Dosage Form Development”
groups, respectively.
The workshop „Continuous Manufacturing” is
successfully organized in cooperation with APV,
International Association for Pharmaceutical
Technology (Arbeitsgemeinschaft für Pharmazeutische
Verfahrenstechnik e. V.).
Highlights 2012/2013
JUL 18
-JUL 19
RCPE offers the course “CFD for Dispersed
Multi-Phase Flows” as part of the ERCOFTAC Best Practice
Guidance Course series.
SEP 26
NOV 02
RCPE’s employee DI Ulrich Rössl wins the Best Poster
Award at the Austrian Proteomic Research Symposium.
The paper „Capsule Filling Operations Using a
Noz-zle-Dosator” receives the Best Presentation Award at
the annual AIChE meeting in Pittsburgh (USA).
NOV 19
Official opening of the new building at Inffeldgasse 13.
DEC 05
RCPE wins the STEP Award 2012 in the category
“Product / Technology”.
MAR 01
The third spin-off of RCPE, SES-Tec OG, is launched.
JUN 30
RCPE successfully completes its 5th business year.
Statements of RCPE’s Stakeholders
Ao. Univ.-Prof.
inMag.
aDr.
inRenate Dworczak
University of Graz
Chairperson of the General Assembly
Deputy Chairperson of the Supervisory / Strategy Board
As symbiosis of research and knowledge transfer facilities for a spe-cific industry, centers of excellence are of benefit to both companies and scientific institutions. Together, we produce cutting-edge knowl-edge while focusing on the market. RCPE combines the strengths of three Graz universities of theoretical and applied research in the field of pharmaceutical engineering, and the resulting success is obvious.
Univ.-Prof. DDI Dr. Dr.h.c. Harald Kainz
Graz University of Technology Member of the General Assembly
Chairperson of the Supervisory / Strategy Board
“With enthusiasm, together to the international top” is the slogan of Graz University of Technology. This slogan reflects the drive and perfor-mance orientation of the 30 Austrian K-centers and K-projects, in which Graz University of Technology is involved. The center of excellence RCPE has successfully established a new and promising research area in Graz. This, together with BioTechMed, in which TUG, Med Uni and KFU unite forces, will contribute to the field of expertise in “Human- & Biotechnology” at our institution.
Univ.-Prof. DI Dr. Wolfgang Pribyl, MBA
JOANNEUM RESEARCH Forschungsgesellschaft mbH Member of the General Assembly
Member of the Supervisory / Strategy Board
Publicly-funded research must become more competitive, and research and industry more closely linked. RCPE is an extraordinarily successful model of how this can be achieved. RCPE is of particular significance to us as an innovation and technology provider in Styria. We provide our core expertise in the fields of bio- and pharmaceutical analysis, study planning, data management and statistics, as well as health econom-ics, to the center and greatly value the large RCPE network of partners from industry and science.
Statements of RCPE’s Stakeholders
Mag.
aDr.
inHenrietta Egerth and Mag. Dr. Klaus Pseiner
Austrian Research Promotion Agency (FFG) Funding Agency
The COMET program is one of Austria’s most successful technology policy initiatives and is internationally recognised as a best practice example. The main goal of the programme is to support cutting-edge research, to promote knowledge and technology transfer and to con-tribute to developing human resources in the Austrian research sec-tor. Funded by the Republic of Austria and the regional governments, COMET Competence Centers are based on a solid network of industry and research partners and are thus ideally placed to conduct scientific research at the highest level.
Ing. Gerd Holzschlag
Styrian Business Promotion Agency (SFG) / Styrian Provincial Government (Land Steiermark)
Funding Agency
Styrian centers of excellence are the innovation engine of Styria. They perform cutting-edge international applied research and provide an important stimulus to the entire economy of the province. Here, the foundations and ideas of the products of tomorrow are developed. RCPE is a prime example of it: the combined forces of science and industry provide the best possible services with a high application po-tential.
Landesrat Mag. Dr. Christian Buchmann
Styrian Provincial Government (Land Steiermark) Member of the Provincial Government
The Styrian R&D ratio of 4.6% is the highest in Austria and Styria was elected as “Entrepreneurial Region of the Year 2013” by the European Union. It is due not only to excellent Styrian scientists but above all to highly innovative enterprises, targeted investments and intense foster-ing of science and research. The R&D contracts generated by RCPE worldwide and flowing into Styria are an excellent and high-quality re-turn of investment.
Foto: © FFG/Spiola
Statements of RCPE’s Stakeholders
Mag.
aDr.
inKarin Schaupp
International Innovation and Business Consulting Executive Consultant
Chairperson of the Scientific Advisory Board (SAB) Member of the Supervisory / Strategy Board
More than ever economy needs synergies arising from the cooperation between companies basic science and research institutions. Centers of excellence like RCPE link science and industry in a perfect way to de-liver innovative results that can be readily applied. I am sure that RCPE will successfully continue to play its role as an intermediary between the research and business worlds in the years to come.
DI Karl-Heinz Hofbauer
Baxter AG
Speaker of the Program Committee
RCPE is a major player in the Styrian regional core field “Health Tech” and a scientific leader with regard to innovation in manufacturing of pharmaceuticals and drugs of the future. There is no comparable re-search institution in the field of pharmaceutical engineering in Europe. RCPE has succeeded in performing cutting-edge research in Austria and collaborating with worldwide pharmaceutical industry leaders.
Mag. Dr. Stefan Liebminger
roombiotic probiotic solutions (RCPE Spin-off)
During my time as a project manager at RCPE I could benefit from its tremendous capacity for innovation. Thanks to the active support of the management and the scientific and industrial partners, I could actually create roombiotic and realize my ideas.
DI Dr. Dalibor Jajcevic
SES-Tec OG (RCPE Spin-off)
I am grateful to have had the chance to work at RCPE because I could accomplish much research and personal development and prepare myself best for independence. Today, I feel ready for challenges and look forward to the future.
Statements of RCPE’s Stakeholders
Univ.-Prof. Dr. Jörg Breitkreutz
Heinrich-Heine-University of Duesseldorf
One of the factors that contribute to the strength of research at the Heinrich-Heine University of Duesseldorf is cooperation with research institutes. The networking of science and industry on the basis of ex-cellent research is essential with that regard. To us, RCPE is a unique research facility in the field of pharmaceutical engineering, with which we would like to continue to cooperate and promote innovation.
Mag. Dr. Thomas Krautzer
The Federation of Austrian Industries (Industriellenvereinigung) Member of the Supervisory / Strategy Board
Science creates the basis of the future development of a country. One hundred jobs in the last five years, many successful projects and the successful bridging between industry and academia testify to the great success of RCPE.
DI Dr. Robert Gfrerer
Human.technology Styria GmbH
RCPE is an excellent example of the strength of the Styrian business region, which is based on the cooperation between science and indus-try. By closely collaborating in the Human.technology Styria Cluster, our companies benefit not only directly from the expertise of RCPE, but from developing competences that will emerge due to being part of the network.
Dr. Jan Oliver Huber
Pharmig (Austrian Association of the Pharmaceutical Industry)
The development of new pharmaceutical products and their manufac-turing processes, as well as the optimization of existing formulations and manufacturing processes, are critical, yet indispensable for the pharmaceutical industry. Supporting innovative and creative pharma-ceutical development processes will ensure medical care for the next generations. RCPE plays an important role in achieving our goal of steadily improving pharmaceutical products and health supply for our patients.
Structure
16
Human Resources and Diversity
Management
20
Key Personnel
24
Key Researcher
26
Organization &
Management
Organization & Management | Structure
Structure
Facts and Figures
87
employees (65.24 FTEs)€ 9M
signed projects’ volume K1 (15 projects)€ 3.3M
signed projects’ volume nonK68
business partners20
scientific partners8
supporting partners3/13
patents granted / patent applications21
doctoral theses in progress5
completed doctoral theses17
master’s theses in progress14
completed master’s theses1
completed bachelor’s paperLegal Structure
RCPE has a flat and efficient organizational struc-ture, which is standard for a non-university R&D facility. There are 2 Managing Directors, who as of July 1, 2013, are assisted by 2 authorized signato-ries. Our Research Areas are supervised by desig-nated experts in the respective fields. In addition, experts working for our scientific partners provide us with technical and content support.
Location
Significant changes took place at RCPE during the last fiscal year. In September 2012, we moved from the old premises on Plüddemanngasse to the Inffeldgasse campus of the Technical Universi-ty of Graz. By relocating to the newly-built Produc-tion Technology Center, RCPE expanded its oper-ational base and further ensured steady growth in the future. The new site offers bigger office and lab space and is ideal for the Center’s research and development activities.
For details regarding RCPE’s state-of-the-art phar-ma product and process science lab, see chapter “Test Facilities and Simulation Tools” on page 48.
Graz University of Technology
65%
JOHANNEUM RESEARCH15%
University of Graz20%
Headquarter RCPE
RCPE organisational structure (2013).
step. Creating an internal structure of junior exec-utives, recruiting several experienced individuals and establishing a two-tier organization via group structuring in the Areas are the essential building blocks of a lean and efficient research company.
Organizational Chart
With more than 80 employees, efficient organi-zational procedures, steady project management and quality assurance become increasingly rele-vant. In that regard, RCPE took appropriate mea-sures, tailored to its size and implemented step by
General Assembly
Supervisory / Strategy Board
Deputy Director
• Area Integration • Scientific Output
• Coordination of International Scientific Appearance • Patents & IPRs
Reporting/Accounting
• Marketing / PR • Human Resources • External Reporting • Accounting / Controlling
Scientific Advisory Board Programm Committee
Programm Commission
CEOs
• Key Account• Strategic Leadership • Scientific Lead• Representation • Internal and external consultingITT1: New Platform Technologies
ITT2: Drug Quality and Safety Technologies ITT3: Personalized Medicine e.g. Geriatrics
Business Development & Scientific Operations
Infrastructure: Laboratory + Process Lab
Area I:
Modeling and Prediction
K1 NonK K1 NonK K1 NonK
Area II:
Products and FormulationsArea III:
Process EngineeringAdvanced Modeling & Simulation Material Science Pharmaceutical Proteins Dosage Form Development Continuous Manufacturing Process Development &
Scale Up QbD / PAT
Three Research Areas
To achieve the goal to “make tomorrow’s drugs possible,“ three research Areas were established in the Center:
› Area I „Modeling & Prediction“ for the development and implementation of computational modeling tools, simulation software and theoretical concepts.
› Area II “Products & Formulations” for products (i.e., product engineering, properties and structuring methods).
› Area III “Process Engineering” for process engineering science (i.e., process design, scale-up, control and optimization).
In addition, RCPE has a QbD/PAT group that fo-cuses on Quality by Design (QbD) and Process Analytical Technology (PAT), their practical
imple-mentation in pharmaceutical development and their applicability to quality- and cost-optimized products and processes.
Moreover, 3 (Area)-Integrating Technology Thrusts (ITTs) were established:
› ITT1 „New Platform Technologies“ for the development of platform technologies for next-generation pharmaceutical products and processes.
› ITT2 „Drug Quality and Safety Technologies“ for advanced quality assurance and control as well as for anti-counterfeiting.
› ITT3 “Personalized Medicine” for the
development of engineering solutions for the manufacturing of personalized solid dosage forms.
Organization & Management | Structure
Area I Area II
QbD / PAT Area III
Organization & Management | Human Resources and Diversity Management
Diversity Management
RCPE’s international orientation extends to its em-ployees: about 17% of them are of non-Austrian origin.
RCPE is committed to increasing the proportion of female employees and improving gender com-petence at the Center. As a result of these efforts, the proportion of women rose to 46% in the fiscal year 2012/2013. One of our major goals is to have Knowledge centers need loyal and motivated
personnel. Their knowledge, experience, enthu-siasm and commitment are the basis of excellent R&D results. In the fiscal year 2012/13, RCPE had on average 87 (previous year: 85) employees, as-sisted by 18 graduate students working on a con-tract basis. As in the previous year, the average employee age was 32 years (as of June 30, 2013). Women comprised 46% (previous year: 44%) of the employees, and the quota of university grad-uates was 58% (previous year: 56%).
RCPE absolute staff numbers and allocation (2008 to 2013).
Human Resources and Diversity
Management
R&D K1 R&D NonK Admin Service Contracts JUL 2008 2009JAN JUL JAN JUL
2010 JAN JUL 2011 JAN JUL 2012 JAN JUN 2013
8
18
39
52
81
86
82
96
99
98
105
Organization & Management | Human Resources and Diversity Management
Our Staff Composition
Our project teams have employees with various educational backgrounds, from pharmacology to process engineering and technical physics. Thanks to this wide range of perspectives, a comprehen-sive analysis of problems can be performed and innovative solutions at the highest level can be found.
Personnel of our industry and scientific partners are regularly and actively involved in numerous projects. Members of partners’ staff often work directly at the Center and our employees tempo-rarily work on the partners’ premises. This type of collaboration delivers the best project results. more women in senior management positions. To
that end, RCPE has established diverse programs, such as flexible working hours and telecommut-ing, to support talented staff members, and wom-en in particular, throughout their professional de-velopment.
To promote young talent, RCPE offers various internship opportunities to school and university students and takes part in such initiatives as “Tal-ente Regional” and Open Door Days (“Schnup-pertage“). RCPE invites young people to its labs to inspire them for a career in research. As “re-search ambassadors,” RCPE employees describe to school students what it is like to be a research-er. Particularly encouraging is the increasing pro-portion of young women who work at RCPE as interns and master’s students.
RCPE staff composition by educational backgrounds (2013).
Biotechnology Others Chemistry Physics Mathematics Informatics Technical Chemistry Technical Physics Mechanical Engineering Chemical Engineering
12%
6%
6%
4%
4%
4%
2%
11%
7%
7%
37%
Pharmaceutical
Sciences
Engineering
37%
Other
Academic
Programs
26%
Organization & Management | Human Resources and Diversity Management
Doctoral and Graduate Degrees
Education and training of students is a priority for RCPE. As interns and graduate students at RCPE, young people can acquire their first experience of working in a research group.
14 completed master theses and 5 completed dis-sertations in the fiscal year 2012/2013 are among the most important achievements of the Center, attesting to the consistent implementation of the training mission of the entire Consortium.
Personnel Development
RCPE has set the following priorities with regard to education and training:
› Promoting the technical and leadership skills that will enable its employees to perform the assigned tasks independently
› Developing and maintaining a high and consistent output quality
› Promoting cooperation within RCPE and creating a motivating work environment › Promoting competent, loyal and responsible
managers
According to the Personnel Development Plan, the proposed employee qualifications are defined during annual performance review meetings. In the fiscal year 2012/2013, RCPE had over 3 train-ing days per employee. Furthermore, other de-velopment opportunities are offered, such as par-ticipating in scientific seminars, colloquiums and workshops.
RCPE staff diversification by gender and work area (2013).
Male Staff
54%
5% admin
49% R&D
Female Staff
46%
9% admin
37% R&D
Organization & Management | Key Personnel
Key Personnel
Prof. Dr. Johannes G. Khinast Scientific Director/Leader DI Georg ScharrerDepartment Head Area I
Dr. Stephan Sacher
Team Leader QbD/PAT
Prof. Dr. José Menezes
Scientific Responsible for QbD/PAT
Dr. Simon D. Fraser
Deputy Director
Dr. Gerold Koscher
Team Leader Extrusion and Downstream
Massimo Bresciani
Director Scientific Operations
Dr. Thomas K. Klein
Managing Director
Dr. Stefan Leitgeb, MBA
Organization & Management | Key Personnel
Winner Fast Forward Award 2010, Category Applied R&D
Organization & Management | Key Researcher
Prof. Dr. Wolfgang Bauer
Paper and pulp technology Fibre characterization Specialty products Assoc.-Prof.in Dr.in Michaela Flock Computational chemistry Material design Property predictions Prof. Dr. Peter Kleinebudde Pharmaceutical technology Solid dosage forms Tablet coating
Prof. Dr. Günter Brenn
Multiphase flows and stability Rheology and rheometry Heat and mass transfer
Prof. Dr. Johannes G. Khinast
Pharmaceutical engineering Multiscale simulation Particle technology
Prof.in Dr.in Gabriele Berg
Biotechnology
Clean room technology Microbiology
Prof. Dr. Christoph Herwig
Integrated bioprocess design Quality by design Integrated biotechnology Prof. Dr. Benjamin J. Glasser Granular flows Powder drying Continuous manufacturing
Prof. Dr. Bernd Nidetzky
Protein technology Biochemical engineering Molecular and applied enzymology
Key Researcher
Prof. Dr. Gundolf Haase
High performance computing Parallel computing algorithms Numerical mathematics
Organization & Management | Key Researcher
Doz.in Dr.in Ruth Prassl
Biophysical chemistry Nanostructure analysis Process monitoring
Doz. Dr. Frank Sinner
Nanoanalytics Biomedical technology Nanosystems Prof. Dr. Robert Schennach Infrared spectroscopy Surface analysis
Prof. Dr. Stefan Volkwein
PDE constrained optimization
Model reduction methods Parameter estimation
Prof. Dr. Andreas Zimmer
Pharmaceutical nanotechnology Drug delivery and drug targeting
Drug formulation
Ass.-Prof.in Dr.in Eva
Roblegg
Solid oral dosage forms Oral biological barriers Extrusion
Prof.in Dr.in Nora Urbanetz
Pharmaceutical technology Particle engineering Pharmaceutical processing
Prof. Jukka Rantanen, PhD
Powder characterization and formulation development Process analytical technology (PAT) and Quality by Design (QbD) Process spectroscopy and multivariate data analysis
Opportunities for Cooperation: Types of
Research Projects
30
Presentation of Selected Research Projects
32
Test Facilities and Simulation Tools
48
Source: Picture taken in the laboratory of the Institute of Biotechnology and Biochemical Engineering, Graz University of Technology
Research | Opportunities for Cooperation: Types of Research Projects
Opportunities for Cooperation:
Types of Research Projects
outside of the K1 Competence Center program. The most important types of NonK projects are briefly described below.
External Funding Projects
RCPE can apply and/or co-apply to national and international funding programs. Of particular relevance are funding programs of the FFG, the Deutsche Forschungsgemeinschaft (DFG) and the Framework Program of the European Union. Thus, projects outside of the sponsored K1 area can also be implemented with a certain element of public funding. In addition, external funding programs are important for positioning RCPE as a research and development organization on the national and European levels.
Contractual Research Projects
Contractual research projects follow a classical contractor/client arrangement. RCPE acts as a contractor and provides specific services to one or more clients. The clients fully cover the costs of the services, without involving any internal or ex-ternal funding. In exchange, the clients receive full rights to the results. Contractual research projects cover a wide span of services and may include small studies (e.g., literature search or an analysis of samples using certain analytical tools) and long-term projects with a project volume of more than a million Euros. Some company partners specifi-cally choose to carry out their project in the NonK area in order to reduce publicity and the formal requirements that a K1 project would entail.
Strategic Partnerships
Strategic partnerships can be implemented if a cli-ent is interested in long-term cooperation rather than a specific service. This cooperation can be a series of individual services integrated into a RCPE offers two basic types of cooperation
proj-ects:
› K1 projects that are implemented within the framework of RCPE’s sponsored project area › NonK projects that are implemented within the
non-sponsored project area.
K1 Projects
RCPE is a K1 Competence Center established as a part of the COMET program initiated by the Fed-eral Ministry of Transport, Innovation and Technol-ogy (BMVIT) and the Federal Ministry of Economy, Family and Youth (BMWFJ). As a K1 Competence Center, RCPE is funded by the FFG, the Styrian provincial government (Land Steiermark) and the SFG. Based on this funding, an overall project vol-ume of approximately 30 million Euros is achieved for seven years.
In the funded K1 project category, the consortia of company and scientific project partners do not cover the entire research-related project costs. Thus, the project costs are effectively reduced. Moreover, receiving the K1 funding does not re-quire time-consuming application procedures (as national and international funding programs often do) and can be accomplished in a straightforward manner if the project proposal fits the scientific focus of the Center and if the project generates new scientific know-how. Thus, K1 projects are an attractive opportunity for partners from science and industry. However, these projects need to be approved by the program commission.
NonK Projects
NonK projects are implemented outside of the sponsored K1 area. The costs are fully covered by the project consortium or may be partly covered by applying for national and international funding
Research | Opportunities for Cooperation: Types of Research Projects
framework agreement. A client may also choose to outsource parts of or an entire task in a specific field of research or development. For long-term cooperation projects, RCPE normally provides access to its equipment and provides staff at re-duced rates. In addition, company partners ben-efit from long-term contacts between their and RCPE’s employees.
Regardless of the way the cooperation is struc-tured, RCPE’s highly-motivated and experienced research team assures fast and efficient execution of the research and development efforts with the goal of maximum customer satisfaction. In sum-mary, we see ourselves as a one stop shop for our customers by providing package solutions for the scientific, research and development challenges of the future.
RCPE areas of business activity.
Customer
Graz University of Technology, University of Graz, Joanneum Research, Heinrich Heine University, Rutgers University, University of Cambridge
Research facilities
e.g., melt extrusion, injection molding, capsule filling, tabletting, fluid bed systems
Industrial Partners
Preferred partners for regulatory submission, clean room technology, GMP lab
One stop shop for...
Connects customers to...
Research
Projects
K1
Funded
and
contractual
research
NonK
Services
Research | Presentation of selected Research Projects
Project manager: DI Georg Scharrer Key researcher: Mag.a pharm.
Eva Faulhammer Dr. Marcos Llusa Type of project: COMET K1
Project
consortium: GlaxoSmithKline Research & Development Limited (UK) Graz University of
Technology (AT) MG2 s.r.l. (IT)
Rutgers University (US)
the low-dose capsule-filling behavior of different powders. The effect of process parameters of a low-dose nozzle dosator capsule-filling machine (Labby, MG2) on fill weight and weight variability of capsules with low fill content (5mg-45mg) was investigated with 12 fine powders, each having defined material attributes.
Utilizing the data generated by this methodology, a model was established by applying multivariate data analysis, and predicting the capsule filling performance of different products with low doses. In addition, critical process parameters and criti-cal material attributes could thus be correlated to critical quality attributes; based on these, a design space was established.
Scientific and industrial relevance of the project
Successful and accurate dosing of low powder masses into pharmaceutical capsules is a chal-lenging task due to the strong dependence of volumetric dosing technologies on material attri-butes. Therefore, it is crucial to develop an un-derstanding how powder properties and process parameters affect the quality attributes of pharma-ceutical capsules (i.e., net weight, weight variabil-ity). Moreover, knowing how powder properties and process parameters affect the capsule quality attributes is particularly important for designing dosing processes for small quantities of powders. State-of-the-art techniques, such as DoE and mechanistic simulations, are applied as part of our Quality by Design approach in understanding
PROJECT
OBJECTIVES
INFORMA
TION
Process Understanding and
Optimization of Dosing and
Filling Systems for Production of
Pharmaceutical Hard Capsules
› To develop an understanding of how process parameters and
powder properties affect the net weight and weight variability
of powder deposited into capsules.
01 SEP 2011 31 AUG 2014
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Research | Presentation of selected Research Projects
Top: The Labby lab-scale capsule filling machine from MG2. It consists of a main product hopper (1), a special rotary container (2) and a small dosator (3). Left: Several nozzles gradually dipping into the powder bed and collecting powder samples (Planeta, an industrial capsule-filling machine).
variability in nozzle dosator machines (paper in progress).
› The effect of capsule filling speed and the ratio between the powder bed’s height and dosing chamber length on plug density and capsule weight variability (paper in progress).
› The effect of process parameters and powder properties on low-dose capsule-filling performance (paper in progress).
› Continuous low-dosage of API (patent in progress).
Utilizing this know-how, capsule filling processes can either be designed for handling powders with certain properties, or properties of particles can be tailored to enhance the performance of specif-ic capsule-filling processes, respectively.
This study is the first scientific qualification of do-sator nozzles for low fill weight (5-45 mg) capsule filling applications. There is no data available in the scientific literature for low dose nozzles so far.
Current project results
› The effect of capsule filling machine vibrations on average fills weight (paper published in the International Journal of Pharmacy).
› The effect of microcrystalline cellulose powder properties on capsule net weight and weight
Research | Presentation of selected Research Projects
Project manager: DI Georg Scharrer Key researcher: Univ.-Prof. Dr.
Gundolf Haase Univ.-Prof. Dr. Johannes Khinast Type of project: COMET K1
Project
consortium: AVL List GmbH (AT)Gebrüder Lödige
Maschinenbau GmbH (GE) Graz University of Technology (AT)
University of Graz (AT)
CFD and DEM (i.e., a full-field CFD-DEM model) makes it possible to simulate such fluid-granular systems. In DEM, the motion of discrete particles is tracked by solving Newton’s second law of motion and in CFD the flow of a continuum fluid is simulat-ed by solving the Navier-Stokes equations, bassimulat-ed on the concept of local averaging. The main ad-vantage of CFD-DEM is that detailed particle-scale information is obtained, including particle trajec-tories and forces acting on individual particles. Efficient coupling methods suitable for large-scale simulations are developed in the project. Further-more, particle phase interaction with complex geometric boundaries, such as mixing tools, screw augers or vessel baffles, will be implemented effi-ciently, keeping the code’s performance high, far beyond the ten million particle limit.
Scientific and industrial relevance of the project
The objective of this project is to develop a new hybrid approach to model gas-solid fluidized beds systems based on first-principles mechanistic meth-ods. Fluidized solid systems are of high relevance to the pharmaceutical industry, e.g., for drying and coating of pellets, or for the granulation of fine pharmaceutical powders to achieve excellent com-pression properties. Recent research showed that complex micro-, meso-, and macro-scale structures in fluidized beds are observed. These structures have strong impact on product quality and thus, a detailed understanding would be beneficial for the understanding, design, optimization and control of pharmaceutical manufacturing processes.
PROJECT
OBJECTIVES
INFORMA
TION
Development of a CFD-DEM Coupling
Method and a Software Prototype for
Simulating Granular Flow with Very
Large Particle Numbers
› Computationally efficient CFD-DEM coupling methodology
› Large-scale mixing process simulations
› Modeling of industrially-relevant process physics (complex
geometry and materials)
01 JUL 2012 30 JUN 2015
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Research | Presentation of selected Research Projects
Top: DEM filling test: 50L mixing device. Geometrical complex multi-part mixing tool represented as a triangle-tessellated CAD surface (pictures at t = 0, 1.2, 8 and 13.5 seconds process time).
Left: Fully two-way coupled fluidized bed simulation: Triple spouts at the bottom. 25 million discrete particles in a raiser configuration.
sults of Van Buijtenen. A very good agreement was achieved. To our knowledge, this is the larg-est simulation of this type world-wide.
Mixing
In order to model real device geometries, a CAD data import module was implemented. Testing of the algorithm’s efficiency for contact detection and search integration of static CAD geometry into the existing DEM framework is in progress. The flexible handling of moving parts (tools, baf-fles, containers) was implemented in the software prototype as well. However, in order to keep cur-rent performance levels, more efficient algorithms will be integrated in future releases. For illustra-tion purposes, a 40L producillustra-tion-scale mixing de-vice is shown in the figure “DEM filling test”. In this project CUDA technology is used for the
GPU-based particle simulations, allowing us to dra-matically exceed the performance of commercially available DEM codes, especially if long-term sim-ulations of mixing processes are to be performed.
Current project results
Coupling
A highly efficient coupling interface technique us-ing “AVL FIRE ACCI” in combination with a hybrid algorithm approach which performs all computa-tionally expensive tasks on the GPU have been developed. This allows for high-fidelity two-way coupled simulations of up to 25 million particles (left figure). The numerical results were also com-pared to the CFD-DEM and the experimental
re-Research | Presentation of selected re-Research Projects
Project manager: Dr.in Sharareh
Salar-Behzadi Key researcher: Prof. Dr. Andreas
Zimmer Type of project: COMET K1
Project
consortium: Cremer Oleo GmbH & Co. KG (GE) HERMES Arzneimittel GmbH (GE)
Innojet Herbert Hüttlin (GE) University of Graz (AT)
The second part of the project devoted to the de-velopment of methods for in-line monitoring of a manufacturing process for the developed coating formulations, using PAT tools. This is in agreement with the PAT initiative of the FDA, which suggests in-line monitoring of pharmaceutical manufactur-ing processes for ensurmanufactur-ing high product quality.
Current project results
Formulation Development:
Lipids are a group of excipients that have recently generated substantial interest for production of a wide spectrum of oral solid dosage forms with im-mediate, controlled or extended release profiles. However, due to their chemical and physical struc-tures, lipids exhibit physical modifications during process and storage, also called “physical aging”, that can lead to stability issues.
For this reason, the formulation development in this project was performed on the basis of a
mechanis-Scientific and industrial relevance of the project
Filling of multiparticulate systems in sticks as “Di-rect to Mouth” dosage form is a substantial prog-ress with respect to increasing the patient com-pliance, targeting both pediatric and geriatric patients with difficulties to swallow. However, using such dosage forms, the unpleasant taste must be masked. Direct taste-masking of API is a response to the population-driven requirements of drug development, demanding easy-to-swallow, taste masked and dose tailored products. In the pharma-ceutical industry, film coating using polymers is the state-of-the-art method for taste masking of solid dosage forms. However, such processing requires enormous amounts of solvents, which makes the process time- and cost-consuming.
The first aim of this project was to develop lip-id-based solvent-free coating formulations with stable release profile for taste masking of API as an innovative and less costly approach.
PROJECT
OBJECTIVES
INFORMA
TION
Rational and Science-Based
Formula-tion and PAT ApplicaFormula-tion Development
for Hot Melt Coating Processes with a
Focus on Taste Masking Applications
› Development of robust formulations for direct coating of API
crystals with QbD concepts.
› Development of PAT strategies for in-line monitoring of the
coating process and for determining the process end-point.
01 OCT 2011 30 SEP 2013
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Research | Presentation of selected Research Projects
Top: Cross section of coated particles
Right: Definition of design space for process and formulation.
Development of In-Line Monitoring Methods: Models have been developed for in-line monitor-ing and end-point determination of the coatmonitor-ing process via NIRS as a versatile and non-destructive tool. Due to the fact, that using NIRS is often af-fected by window fouling, we have also success-fully developed a novel mathematical solution to this problem.
In addition, a model was developed for the applica-tion of a multipoint-NIR-system for in-line monitor-ing of coatmonitor-ing processes. This method can be used to simultaneously monitor the coating process at several positions inside the fluidized bed coater, with the benefit of faster detection of non-uniform coating during the process. The model was also successfully used for determing the process end-point.
The formulation and the developed model for in-line monitoring of the process were successfully up-scaled.
tic understanding of the physico-chemical behav-ior of lipids. Coatings with different polymorphic characteristics have been produced. Afterwards, the impact of process parameters and storage con-ditions on the polymorphic behavior of lipids, sur-face of the coatings and release profile of API were systematically studied. Moreover, methods were developed for a quantitative evaluation of the taste masking. In addition, the transformation of the less stable α-form to the stable β-form was analyzed by heat treatment of coatings consisting of α- form. It was observed, that the deformation energy re-leased by phase transformation from α to β-phase leads to structural changes. Alterations in the taste masking and release profile of APIs were also ob-served after heat treatment. The gathered knowl-edge was used to develop suitable coatings with stable polymorphic behavior and desired quality attributes. The developed product shows an excel-lent flowability, providing a trouble-free packaging of multiparticule dosage form. The perfect taste masking improves the patient adherence.
Research | Presentation of selected Research Projects
Project manager: DI Dr. Simon D. Fraser, ppa. Key researcher: Prof. DI Dr.
Bernd Nidetzky Type of project: COMET K1
Project
consortium: Graz University of Technology (AT) Kaiser Optical Systems, Inc. (FR) Zeta Biopharma GmbH (AT)
tems on the other hand comprise those factors and offer wide influence on heat transfer, tem-perature and even mixing. Optimal conditions for freezing, storage and thawing vary depending on the characteristics of the protein, buffer, excip-ients and their concentrations whereas cooling and heating rates have effects on the ice surface exposure of proteins.
The aim of this project therefore is to develop a system for controlled F/T in the sub-liter scale. Special focus is on process understanding (assist-ed by CFD simulations) and process control (tem-perature, pH, Raman spectroscopy). Besides the system itself new insight and process understand-ing for the F/T process are expected.
Scientific and industrial relevance of the project
Freezing is a common and convenient means of storing pharmaceutical protein solutions at indus-trial scale. It serves to increase flexibility of the manufacturing process with respect to short- or medium-term market demands. Despite its seem-ing simplicity F/T can form a critical unit process. Losses of valuable protein in the form of aggre-gation or inactivation can add up to 60%, even in few mL volumes. Cryoconcentration and surface exposure are even more pronounced when bulk volumes in the range of some 100 mL to several 100 liters are frozen. Bottles or plastic bags are frequently used to store products at liter scale in simple freezers operated at constant tempera-tures. Here, process surveillance and control are largely neglected. Integrated bulk freezing
sys-PROJECT
OBJECTIVES
INFORMA
TION
Optimization of Freeze/Thaw behavior
of pharmaceutical proteins
› Development and construction of a fully controllable 700 ml
freeze container
› Development of a process control strategy including Raman
spectroscopy
› Establishment of a scaling procedure for freezing process and
equipment
01 JUL 2012 31 DEC 2013
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Research | Presentation of selected Research Projects
Right: 700 ml container for controlled freezing and thawing of pharmaceutical proteins constructed by Zeta Biopharma. Bottom: Cryoconcentration of FITC-labeled protein employing different ice-front evolution velocities using Cryo – Confocal Laser Scanning Microscopy.
Another focus of this project is to move away from a black-box process towards a more transparent freezing process. Therefore, several probes have been included in this system. Temperature map-ping is used for the simultaneous recording of temperatures at different regions of the contain-er yielding not just a single tempcontain-erature, but an overall distribution. The value of Raman spectros-copy for the monitoring of the freezing process is currently investigated and has already shown very promising results.
The remaining time of the project will be used for a demonstration of the capabilities of the system and for the definition of a design space. Rules for scaling of process and equipment will be estab-lished and the work using the Raman probes will be refined.
Current project results
The influence of F/T on proteins has been thor-oughly investigated and critical product attributes have been identified for different protein classes (Monoclonal antibodies, Cytokines). The effect of varying process conditions has been demonstrat-ed in the small scale both on macroscopic, micro-scopic (bottom figure) and molecular level. The knowledge gained was the basis for a systematic F/T process development for a model protein in the newly-constructed freeze container.
The 700 ml freeze container (top figure) has been developed and constructed by Zeta Biopharma together with the project team using the knowl-edge gained through process simulation. The identification of critical process parameters is cur-rently ongoing.
Research | Presentation of selected Research Projects
Project manager: DI Dr. Stephan Sacher Key researcher: Prof. Dr. Johannes G.
Khinast Type of project: COMET K1
Project
consortium: RECENDT GmbH (AT)
tools do not provide any information about intra- and inter-tablet coating uniformity, which are key parameters of a tablet coating process.
These disadvantages can be overcome by means of OCT, which additionally features short acquisi-tion and processing times, high spatial resoluacquisi-tions and high sensitivity. Goal of this project is the im-plementation of an OCT system in an industrial coating process enabling the analysis of the coat-ing thickness and homogeneity in real-time.
Current project results
In the first year of the project, a specification for an industrial OCT system has been developed including assessment of all risks and process pa-rameters. Development and design of a suitable pharma sensor is ongoing.
Scientific and industrial relevance of the project
In the pharmaceutical industry, the desired amount of coating is controlled by an adjustment of the process time, which is set based on em-pirical knowledge. The coating thickness itself as well as its quality is only controlled off-line at the end of the manufacturing process. Due to a lack of established techniques homogeneity is only mea-sured rarely.
As far as in-line monitoring of tablet coating thick-ness is concerned, there exist different process analytical technologies, which have been inves-tigated at a scientific level. State-of-the-art mea-surement systems such as near-infrared or Raman spectroscopy do not yield an absolute value of the coating thickness and have to be calibrated based on primary measurements. Moreover, these
PROJECT
OBJECTIVES
INFORMA
TION
Optical coherence tomography for
non-destructive inline tablet coating
analysis
› Development of a pharma conform OCT sensor
› Development of an algorithm, which enables in-line calculation
of characteristic tablet coating parameters from a statistically
representative number of measurements
› Implementation of the system in a pharmaceutical tablet coating
process
01 JUL 2012 30 JUN 2015
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Research | Presentation of selected Research Projects
Left: Off-line OCT measurements of various commercial tablet products. Top: Implementation of an existing OCT system in the fluid bed coating apparatus at RCPE technical lab.
when tablets pass the inspection window of the OCT sensor head. After selecting solutions for a suitable mounting position of the sensor head the influence of moving tablets on the measurements was investigated theoretically and experimentally. However, in-line investigation of the coating quali-ty within manufacturing requires the development of an automatic evaluation procedure. Most of the remaining project time will be used to develop a software package and evaluation algorithms to allow 100 % real-time quality control. Finally, the OCT sensor head will be integrated in a pan coat-er and the entire system will be tested.
To reveal the high potential of OCT as process analytical technology, off-line data using commer-cially available tablets (see left figure) were gen-erated. Based on the achieved knowledge basis how to operate OCT for pharmaceutical investiga-tions, the very first in-line tests were started. Sev-eral experiments in a fluidized-bed coater were continuously monitored by means of an existing OCT system, which can be seen in the top figure. The measured data are currently analyzed and compared to off-line reference measurements, which were performed by both off-line OCT and image analysis with QICPIC.
Besides those experimental runs the focus of the project was put on automatic evaluation of mea-surements under consideration of the sensor po-sition and the speed of the tablets in the coater (~0.5 m/s), which influences the measurements,
Research | Presentation of selected Research Projects
01 JUL 2012 30 JUN 2015
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Project manager: DIin Diana Dujmovic
Key researcher: Prof. Dr. Johannes G. Khinast
Ass.-Prof.in Dr.in Eva
Roblegg Type of project: COMET K1
Project
consortium: G.L. Pharma GmbH (AT)Graz University of Technology (AT)
Leistritz Extrusionstechnik GmbH (GE)
milling or spray drying of the drug. One issue here is that these nano-particles tend to agglomerate. An innovative new way to prevent the achieved nano particles from agglomeration is producing a solid dispersion by hot melt extrusion. Especially for drugs with a high melting point this is a suitable method. A water-based nano-suspension is pro-duced, e.g., by wet milling and stabilized by the addition of a stabilizer. These nano-suspensions can be easily dosed by a pump into the extrud-er. During extrusion, water is evaporated and the particles are incorporated in a dispersed form in the polymer matrix. Although HME is known from polymer manufacturing since decades, there is still a lack of understanding and rational methods for design, optimization and scale-up. Experimental studies on mixing effects along the screws (and other important quantities, e.g. local melt tempera-ture) are strongly limited due to the inaccessibility
Scientific and industrial relevance of the project
Over 90 % of today’s drugs under development are poorly or not water soluble (BSC II and BSC IV). Therefore, the pharmaceutical industry is forced to develop possibilities for increasing the solubility of such drugs to achieve greater bioavailability. Dis-solving drugs in a molten polymer matrix is a prom-ising method. One technology to establish solid solutions is HME. Thereby, the raw materials are mixed and molten, e.g., by a twin screw extruder. The produced melt is then shaped into pellets or tablets by downstream processes like strand pellet-izing, die phase pelletizing or injection moulding. One challenge of this method could be recrystal-lization of the molten API. Another possibility to enhance the solubility is the increase of the specific particle surface by decreasing the particle size to nano scale. Common methods to reduce the par-ticle size are high-pressure homogenization, ball
PROJECT
OBJECTIVES
INFORMA
TION
Novel Approaches in Pharmaceutical
Hot Melt Extrusion
›
Exploring manufacturing possibilities of so-called ‘’Nano Extrudates’’
by the addition of ‘’Nano Suspensions’’ to a molten polymer matrix by
Hot Melt Extrusion.
›
Definition of necessary process equipment (screw configuration,
vacuum degassing, dosing systems)
›
Develop standardized methods for characterization of raw materials.
›
Evaluation of possible downstream processes for shaping e.g.
injection moulding.
›
Establishment of mechanistic understanding of the mixing process by
3D Simulation
Research | Presentation of selected Research Projects
Top: 3D simulation of the mixing process.
Left: Nanoparticles incorporated in the extrudate.
› Formulation and characterization of stable nano suspensions.
› Adaption and refurbishment of the existing Extruder.
› Production and characterization of first nano extrudates.
› Screening of possible codes for 3D Simulation, selection of “LIGGGHTS”.
› Development of a novel interaction method for solid walls with SPH fluid elements, suitable for complex geometries in the *.stl format.
› Development of a gap model to overcome the resolution problem in tight gaps.
› Validation with conventional CFD-data from literature for the simplified case of Newtonian, isothermal flow in a fully-filled screw section. › Detailed description of cross- and axial mixing in
different operation states for the validation case. of screw extruders. Simulation approaches offer the
opportunity to analyze and visualize the melt flow and the corresponding mixing effects in detail. The simulation of mixing processes in different types of screw elements of co-rotating twin-screws is still a challenge due to partially filled screw sections. To overcome this problem, this project includes the development of a novel simulation method based on Smoothed Particle Hydrodynamics (SPH), which provides high potential for mixing and free-surface flows in complex, moving geometries.
Current project results
› Selection of three model APIs.
› Characterization of a first model substance (Phenytoin) by selected methods.
› Selection of possible stabilizers for the nano suspension production.
Research | Presentation of selected Research Projects
01 JAN 2013 31 DEC 2016
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Project
manager: DI Georg Scharrer Key
researcher: Prof. Ajith AbrahamProf. Crina Grosan Prof. Dr. Johannes G. Khinast
Prof. Peter Kleinebudde Dr. Torsten Kraft
Prof. Aleksander Mendyk Dr. Abder Michrafy Prof. Vaclav Snasel Prof. Hugh Stitt Prof. Dr. Chuan-Yu Wu Type of
project:
International funded project
world-leading universities, 2 national research in-stitutes, and 8 private partners (including 4 SMEs), through a coordinated research and training pro-gram. The partner’s vision is to develop robust in silico process models that can be used to predict the properties of intermediate (ribbons/granules) and final products (tablets/pellets/components). This prediction is based on the properties of in-dividual particles and identified optimal process conditions and formulations. The final result will be an innovative and economic tool for product development, especially for high value-added products. The model will be developed through thorough process understanding and synergy of a range of advanced modeling techniques (e.g.
Scientific and industrial relevance of the project
Particulate materials, e.g., pharmaceutical formu-lations, precious metals, fine chemicals, metal & ceramic powders, are compacted to produce a wide range of products in a number of industrial sectors. The diversity of the used materials and the complexity of the manufacturing processes make it a challenging task for product development and process design. In particular, manufacturing of high value-added products (such as pharmaceu-ticals and catalysts) are constrained by a number of scientific and technology hurdles. IPROCOM will address these challenges by bringing to-gether 4 leading European research groups from
PROJECT
OBJECTIVES
INFORMA
TION
The development of in silico process
models for roll compaction
›
The main goal of this project is to investigate roll compaction by
means of experimental, modeling and simulation efforts.
›
An additional goal is to train young scientists in the relevant fields and
to give them the opportunity to exchange experience and knowledge
with each other and with experienced researchers during frequent
meetings and trainings.
Project consortium:
AstraZeneca UK Limited (UK)
Universitatea Babes-Bolyai, Cluj-Napoca (RO) Centre National de la Recherche Scientifique (FR) Fraunhofer Gesellschaft zur Förderung der angewandten Forschung e.V. (GE)
Heinrich-Heine-University Düsseldorf (GE) Jagiellonian University (PL)
Johnson Matthey plc. (UK) University Of Surrey (UK)
VSB-Technical University of Ostrava (CZ) Associated partners:
Ark Media Productions (UK)
L.B. Bohle Maschinen + Verfahren GmbH (GE) SkillStudio Limited (UK)
Research | Presentation of selected Research Projects
Particles
Products
Mixing Powders Roll com pactio n Rib bo ns Die compaction Granules
Millin g
1. Develop robust in silico
process models to predict the
properties of intermediate and
final products based on the
properties of individual particles
2. Provide structured training
for the next generation
of researchers who will
comprehend such models,
associated knowledge and
techniques and apply them to a
number of particulate products
manufacturing industries.
Top: Visualization of how IPROCOM’s main topic, roll compaction, fits into the production process of pharmaceuticals
Right: Logo of the Marie-Curie-International training network which funds IPROCOM
given at RCPE in Graz beginning of 2014. During this training the researchers get an overview of all the relevant tasks for the project, by lectures of experienced researchers and through a lab course with hands-on training.
After the training, all researchers will start to work on their topic and exchange information on a reg-ular basis and during planned visits at involved partners sites.
FEM, DEM). Our vision will be realized through close collaborations among the partners involved in this multidisciplinary IPROCOM consortium. The consortium contains experts of complementa-ry areas and possesses a broad range of research infrastructures. This will be further enhanced by training a cohort of 12 PhD students and 3 Post-Docs, who will be the next generation technology leaders.
Current project results
Currently, employment of researchers started and will be finished at end of 2013. The first training for the researchers, one full week, is going to be
Research | Presentation of selected Research Projects
01 MAR 2012 28 FEB 2015
1 JUL 2012 30 JUN 2013 FISCAL YEAR
Project manager: Dr. Gerold Koscher Key researcher: DI Wolfram Irsa
Prof. Dr. Johannes G. Khinast Ass.-Prof.in Dr.in Eva Roblegg Prof. Dr. Georg Steinbichler Type of project: Nationally-funded project
Project
consortium: Engel Austria GmbH (AT)FH Joanneum – University of Applied Sciences (AT) Johannes Kepler University Linz (AT)
University of Graz (AT)
Injection molding is similar to hot-melt extrusion. However, the hot material is immediately injected into the mold, thus producing tablets in one step. Injection molding, during which matrix material, API and additives are mixed on a molecular level and then injected into the designed mold under high pressure, is known to be an effective and cost-efficient method of advanced manufacturing. Since it is known that pellets (but not tablets) can be produced via hot-melt extrusion, the goal of the project is to research injection molding as an innovative and flexible technology for producing a final pharmaceutical product in one step.
Current project results
Injection molding combines the advantages of a hot melt extrusion process (increased
solubili-Scientific and industrial relevance of the project
More than 40% of all new (90% of all future) active pharmaceutical ingredients (APIs) are considered poorly soluble. As solubility is a prerequisite for absorption into the body, novel processes and formulations must be developed to enhance the bioavailability of even poorly soluble substances. Hot-melt extrusion is a solvent-free process that makes it possible to produce pellets of (i) poorly soluble or (ii) bitter substances with a predefined release profile. During hot-melt extrusion, a matrix material (typically a polymer), API and additives (such as plasticizers, tensides or anti-tacking com-pounds) are mixed on a molecular level at elevat-ed temperatures and extrudelevat-ed. Additional steps are carried out to convert the hot-melt strand from the extruder into a tablet or a capsule.
PROJECT
OBJECTIVES
INFORMA
TION
Injection Molding of Pharmaceutical
Application Forms
› Demonstrating the principle suitability of injection molding
for the production of pharmaceutical dosage forms based on
selected m
