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  • PEARRL Project
    • Beneficiaries
    • Partner Organisation
    • People >
      • Supervisors >
        • Prof. B. Griffin
        • Prof. M. Kuentz
        • Dr. C. Saal
        • Dr. L. Kalantzi
        • Dr. E. Kostewicz
        • Prof. C. Reppas
        • Prof. J. Dressman
        • Dr. N. Fotaki
        • Dr. R. Holm
        • Dr. M. Vertzoni
        • Dr. K. Box
        • Prof. C. O'Driscoll
      • Researchers >
        • Niklas Köhl (ESR1)
        • Felix Ditzinger (ESR 2)
        • Daniel Price (ESR 3)
        • Georgia Tsakiridou (ESR 4)
        • Sandra Jankovic (ESR 5)
        • Chara Litou (ESR 6)
        • Christina Pentafragka (ESR 7)
        • Rafael Leal Monteiro Paraiso (ESR 8)
        • Laura Henze (ESR 9)
        • Patrick O'Dwyer (ESR 10)
        • Marina Statelova (ESR 11)
        • Mariana Guimarães (ESR 12)
        • Ioannis Loisios-Konstantinidis (ESR 13)
        • Alexandra-Roxana Ilie (ESR 14)
        • Angela Effinger (ESR 15)
      • Scientific Advisory Board >
        • Prof. Carla Caramella
        • Dr. Paul Dickinson
        • Dr. Andrea Edginton
        • Dr. Susanne Keitel
        • Dr. Mehul Mehta
    • PEARRL Wiki >
      • FAQ
      • Glossary
  • Research
    • Workplan
    • WP1: Bio-enabling formulations
    • WP2: Biopharmaceutical tools
    • WP3: In silico methods
    • Results >
      • Scientific Publications
      • Conference Contributions
      • InfoPEARRLs
      • Media
  • Training
    • Local
    • Network-wide
    • PEARRL Online Learning Portal
    • Member Area
  • News
  • Events & Meetings
    • Webinar: Regulatory Science Apprentice
    • Annual Meeting 2019
    • Model Informed Drug Development Symposium 2019
    • Annual Meeting 2018
    • Regulatory Science Symposium 2018
    • Annual Meeting 2017
    • Regulatory Science Symposium 2017
    • PEARRL Calendar
    • International Conferences

Interview with Daniel Price (ESR3)

5/18/2021

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1. What has your research project focused on and what are your key results and innovations coming from your research project?
The main focus of my research project was to develop new experimental and computational tools to develop solubility-enhancement formulations. To put it more simply: how can we improve efficiency in the drug development process? The main highlight from my research was the development of a new computational workflow which reduced the experimental time required to select a crucial formulation component (precipitation inhibitors) by up to 90%. 
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2. What impact does your research project and your outcomes have?
Computational pharmaceuticals is a potentially paradigm shifting approach to formulation development. Already we are seeing the huge impact that computational technologies (e.g. AI and machine learning) can have in drug discovery, but in drug development we are still in the early stages.  As a first step, our work on the use of quantum mechanics and computational chemistry has inspired further work on this technology. For example, one of the projects I am currently leading will roll-out this approach to several other areas of formulation development. The blue-sky goal is that, in the future, 75% of formulation development will take place “in silico”, screening vast databases of formulation combinations at break-neck speeds.  Such a drug-development process would decrease time to market, lower the overall cost of drug development and provide quicker and cheaper access to life-saving medicines for patients.
 
3. What were your personal highlights over the course of your research project?
For me the biggest highlight was being a part of an inter-disciplinary and multi-cultural network. In the PEARRL program I have forged strong bonds and friends for life. To put this into perspective, I am continuing to work with several of my PEARRL colleagues on innovative and exciting projects such as those mentioned above. The second highlight is the spring-board effect that PEARRL has had on my career development. As a PhD student based in Merck, working on Merck technologies, I was well-placed to enter into a full-time role at a higher level than would normally be feasible as an external PhD applicant. Furthermore, the skills I have honed throughout the PEARRL project (especially with a focus on soft-skills and collaboration) continue to accelerate my development within Merck.
 
4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
As alluded to above, the involvement of industry is crucial. My advice for any aspiring PhD student is to look for projects with close links to industry. Even if you are on an academic career path, close contacts and deep understanding of the industrial mindset is highly beneficial. Secondly, the focus on soft-skills, personal development and collaboration was crucial, and should be a cornerstone of any PhD program, local or otherwise.
 
5. How did the PEARRL network impact your doctoral experience?
My entire doctoral experience was the PEARRL network, so to put it quite simply I couldn’t imagine doing a doctorate any other way. From day one I felt privileged to be part of an exciting, dynamic and collaborative network. Without the PEARRL network, I doubt I would be on my current career path and I would not have met so many good friends and (hopefully) regular collaborators.  
 
6. What are your plans for the future?
For the past two years I have been working within Merck Life Science as a strategic marketing manager. I am responsible for marketing strategy and execution for a portfolio of products and services. In this role, I am leading several innovative projects including: digital formulation development, 3D pharmaceutical printing and novel modalities for solid formulation. In the future, I would like to evolve into an executive management role within life science. On the path to this goal I would like to gain further experience in different areas of our business (e.g. commercial), and perhaps further my education via an MBA.  
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Interview with Christina Pentafragka (ESR 7)

1/13/2021

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1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research project has focused on understanding the gastrointestinal (GI) drug transfer and GI contents’ composition under fed state conditions, and exploring areas for improving the simulation of relevant processes and characteristics in vitro.
Towards this end, a clinical study was performed to collect samples from the stomach and the upper small intestine of healthy adults after administration of two model drugs and the standard meal suggested by regulatory authorities (FDA, EMA) to induce fed state conditions in bioequivalence/bioavailability studies. Drug levels were measured to inform on the GI drug transfer process. In the same time, physicochemical characteristics of luminal contents that are relevant to oral drug absorption were quantified. In addition, experiments with TIM-1, a multi-compartmental dynamic model mimicking the upper and middle GI tract, were performed to evaluate reproducibility of the clinical study data.
 
2. What impact does your research project and your outcomes have (in your field of research, in drug development, any benefits for the general public etc.)?
Only few publications are available in literature to date on the GI drug transfer process in the fed state.
Characteristics of luminal contents such as the buffer capacity, osmolality, viscosity, lipid species’ and bile acids’ content were measured for the first time after administration of the standard meal.
Suggestions on how to address the GI drug transfer process and luminal characteristics after the standard meal in in vitro methodologies were made, based for the first time on actual luminal data. Specific comments for improving the in vivo relevance of TIM-1 data under fed state simulating conditions were also made.

3. What were your personal highlights over the course of your research project (training, results, awards, networking etc.)?
Being part of a European-wide training network bridging academia, industry and regulatory authorities was the highlight of my PhD. Insight into all three sectors allowed for developing a multidimensional skillset that helped me launch my project and is also invaluable to my professional career. Collaboration with prominent scientists and highly motivated fellow ESRs within the network was priceless. The opportunity to attend international workshops and conferences was another incontestable asset of the programme.
 
4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
Both the regulatory and industrial secondments were among the greatest of opportunities offered within PEARRL. Much as industrial collaborations are regularly part of doctoral projects, the regulatory part is rarely given similar attention. My personal short experience in BfArM definitely provided me with very instructive training, allowing me a clear and more spherical view on medicines’ regulatory matters that should be proven useful to my future career.
 
5. How did the PEARRL network impact your doctoral experience?
The PEARRL network markedly benefited my doctoral experience through all the above mentioned opportunities offered. In the end of this PhD adventure, I would like to extend my sincere and heartfelt gratitude towards all the members of the consortium for the constructive advice, cooperation, fruitful scientific discussions, knowledge exchange, and friendship during the project.

6. What are your plans for the future?
I have recently started a position in the Clinical Research Department of ELPEN Pharmaceutical Co. Inc. in Greece, where I can apply many of the skills acquired during my PhD.
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Interview with Marina Statelova (ESR 11)

1/13/2021

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. What has your research project focused on and what are your key results and innovations coming from your research project?
My project focused on the development of patient-centric biopharmaceutics testing, specifically, new in vivo and in silico tools and methodologies were proposed to evaluate paediatric formulations. Currently, bioavailability and bioequivalence studies for paediatric formulations are mainly performed in healthy adults following protocols applied for adult drug products. An exploratory bioavailability study in healthy adults was designed and performed to understand the impact of age-specific foods on oral drug absorption for the first time; next, a physiologically based pharmacokinetic (PBPK) modeling approach to translate the data acquired in adults to the target paediatric population was proposed. Additionally, bioavailability data acquired from a preclinical animal model (Beagle dogs) applying different dosing conditions were evaluated regarding their usefulness to inform paediatric drug product development in combination with PBPK modeling and to predict formulation performance in paediatrics.

2. What impact does your research project and your outcomes have?
Development and availability of biopharmaceutics tools is of paramount importance in populations where clinical testing in the target population is limited by ethical concerns. The proposed study design and PBPK modeling workflows can contribute to the biopharmaceutics risk assessment for paediatric medicines, which would further facilitate the development of safe and effective paediatric medicines. The proposed workflow could accelerate paediatric product development timelines, resulting in faster access to medicines specifically tailored for the different age groups of paediatric patients.  

3. What were your personal highlights over the course of your research project?
The training and networking opportunities from the PEARRL consortium were a highlight for me, as they helped me grow professionally and gain new skills and knowledge. The PEARRL Wisdom Weeks provided a unique platform to share recent scientific advances from each project, receive constructive feedback from the experts in the pharmaceutical field, and above all encouraged networking and collaborations within and outside the PEARRL consortium. During my industrial and regulatory secondments, I gained valuable insights into different fields of pharmaceutical sciences within a dynamic environment with scientists from different backgrounds, which has been beneficial for improving team-working abilities and cross-functional collaborations.

4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
The training received on PBPK modeling and regulatory sciences are highly relevant for a successful and efficient pharmaceutical development. PBPK platforms have immense potential to inform drug product development not only for adults, but also for special populations and different patient groups. Furthermore, knowledge in regulatory sciences can be integrated throughout the development process, which would facilitate regulatory evaluation, increase chances for approval and ensure the needed medication reaches the patients.
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5. How did the PEARRL network impact your doctoral experience?
The PEARRL network had a huge impact on my doctoral experience, as the PEARRL team atmosphere was present from the very beginning. From professional point of view, it provided an opportunity to discuss the course of the scientific work with experts from the biopharmaceutic and pharmaceutical field who offered invaluable constructive feedback. The PEARRL trainings and the presentations from fellow scientists broadened my knowledge on different aspects of drug formulation and biopharmaceutics evaluation, which will be undoubtedly helpful for my future career path. Last but not least, PEARRL introduced me to like-minded and motivated scientists from different countries, whose ultimate goal was to improve patient’s lives through innovation.
6. What are your plans for the future?
I recently joined Novartis AG as a Senior Expert Data Scientist within the Biopharmaceutics Team. In this role, I will be not only contributing to medicines development with the knowledge and skills gained during my PhD studies, but will be able to further develop my expertise in the field.
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Interview with Alexandra-Roxana Ilie (ESR14)

9/17/2020

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We would like to congratulate Roxana who has recently successfully defended her PhD. Within the PEARRL project, Roxana's individual project focused on establishing a biopharmaceutics tool to investigate the in vivo performance of supersaturated SNEDDS, useing the in vitro understanding to develop an in silico model to predict the in vivo performance and comparing the in vitro and in silico predictions to observations in vivo. In a short interview Roxana explains more about her project and the impact of PEARRL on her research and training.

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1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research project was focused on the design and development of supersaturated lipid-based drug delivery systems (sLBDDS) for applications in pharmaceutical industry. Given that many novel drug candidates in pipelines are poorly water-soluble drugs, development of bio-enabling strategies such as sLBDDS are needed. Supersaturated lipid systems have the advantage of low-tech manufacturing methodology, ability to load high drug concentrations and improved drug absorption via excipient-mediated effects relative to conventional formulations. The work in my research project showed that sLBDDS can be designed for a range of poorly water-soluble drugs, that should have good lipid solubility and a high glass forming ability. Furthermore, it was concluded that simple one or two component lipid systems have the advantage of streamlining drug development processes and the better performance in comparison to more complex three component systems was shown. Furthermore, the use of two in vitro dispersion/digestion-permeation models has been successfully investigated with sLBDDS. Optimizations such as inclusion of precipitation inhibitors in sLBDDS improved drug absorption of cinnarizine, a drug which presented poor stability in lipid systems. To sum up, the work tackled three research pillars of design, development and optimization of supersaturated lipid-based drug delivery systems.    
 
2. What impact does your research project and your outcomes have? 
The different insights into design, development and optimization of supersaturated lipid-based drug delivery systems in a pharmaceutical industry setting sparked the interest of formulation scientists for such technology. The guidance maps and flow charts presented in my PhD thesis will be shared with the different groups in R&D and will serve as starting point for further development of these lipid systems. These will potentially determine inclusion of sLBDDS as formulation options in preclinical and clinical testing and will advance the development in the field. 

3. What were your personal highlights over the course of your research project?
To me, the whole PERAAL experience was like a “dream come true” since I always wanted to do a PhD project in pharmaceutical industry. Even though in some aspects I missed the academic student life, the leanings I got from my colleagues in Janssen Pharmaceutica were of immense importance for my development. I feel that I was shaped as a rigorous scientist, who can handle different scientific or practical challenges, pays great attention to details and is always ready to “advertise” the research in order to set-up novel experimental designs. Several workshops and courses were also very relevant and covered very important topics such as development of scientific writing competencies, presentation and communication skills.
 
4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
From PEARRL, I enjoyed the most the possibility to go on secondments. I think inclusion of these are a fantastic idea. For me both the regulatory secondment at the Medicines and Healthcare products Regulatory Agency and at the University of Southern Denmark were exceptional experiences where I learned so many novel skills, interacted with very interesting people and also expanded my experimental results and publications portfolio.

5. How did the PEARRL network impact your doctoral experience? 
The PEARRL network greatly benefited my doctoral experience from both professional and personal perspectives. From a professional point of view, I enjoyed a lot sharing my research at international conferences or during symposia, discussing my results and identifying opportunities for improvement. Getting to know so many highly educated people enriched my ability to communicate, to network and create strong interpersonal connections.   

6. What are your plans for the future? 
After my PhD, I returned to my home country, to bring some of the knowledge accumulated internationally “back home” and to add value to social and professional aspects in Romania. I will soon start a position at a Romanian pharmaceutical company as Formulation and Analytical Scientist. This will allow me to continue my career in R&D, while advancing my knowledge in late stage drug development processes and manufacturing technological transfers for Parenterals.

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Interview with Laura Henze

9/4/2020

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Laura Henze has recently successfully defended her PhD online on exploring the utility of the porcine model for predicting bio-enabling oral drug products performance in humans. We have taken this opportunity to ask her some questions in an interview on her research, her experience in PEARRL and her plans for the future.
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1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research project focused on the suitability of the pig as a preclinical model in oral drug product development. We established in vitro- in silico models for the pig that improve interpretation of preclinical results which can streamline the drug development process.
 
2. What impact does your research project and your outcomes have?

The pig biorelevant medium developed as part of this work will be hugely beneficial to industry during the drug development process, streamlining early phases in preclinical development phases. Obtaining relevant information at an early stage of development facilitates a more efficient development process, which can save time and money for industry, as well as enabling earlier access of patients to new medicines. By incorporating species specific in vitro – in silico tools, a better understanding of the factors affecting the performance of the drug can be achieved. This should help to reduce the number of animals required in the future, highly beneficial from both a resource and ethical point of view.

3. What were your personal highlights over the course of your research project?
The training provided within the PEARRL project helped me to continue to develop and progress professionally by gaining new skills and knowledge. It was a great experience to work in an international network with experts in the field, with an added benefit of getting very constructive feedback to improve your research, and discuss the latest results of your research. In addition, it was a great opportunity to build collaborations between all the projects, work packages and partners involved in PEARRL. Several conferences and workshops gave us an opportunity to present and talk about our research.

4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
I think the regulatory secondments were a great part of the PEARRL project. I really enjoyed my secondment at the HPRA in Dublin, it was great to experience the regulatory environment. Further training provided at the PEARRLs of wisdom weeks were hugely enjoyable.

5. How did the PEARRL network impact your doctoral experience?
Being part of the PEARRL network hugely benefited my doctoral experience, a key part was European wide network that combines academia, industry and regulatory authorities. Especially the chance of being in contact and getting feedback from experts around the globe improved my work enormously.
 
6. What are your plans for the future?
I have recently started a position as a Postdoc at Janssen Pharmaceutica in Beerse Belgium, as part of the Dissolution Sciences team.
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Interview with Sandra Jankovic

9/3/2020

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Sandra (ESR5) has been studing computational methods and novel in vitro tools according to their suitability to support the development of solid dispersions. She recently successfully defended her PhD and we held a short interview with her to find out more about her experience within PEARRL.

1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research project was about new analytical approaches for solid dispersion characterizations. Solid dispersions are one of the technologies employed to improve the apparent solubility of poorly soluble drugs. In my dissertation thesis I worked on Fluorescence Spectroscopy and Diffusing Wave Spectroscopy and show their potential as a novel approaches to gain a deeper understanding of both manufacturing but also dissolution behavior of amorphous solid dispersions.

2. What impact does your research project and your outcomes have?
There is still a lack of understanding of the dissolution behaviour of ASDs so there is a high need for novel analytical approaches mainly for the drug development.

3. What were your personal highlights over the course of your research project? 
I improved my presentation and writing skills and at the same time living abroad gave me the opportunity to learn a new culture and new research approaches.  What I liked most about the Marie Curie Fellowship is the opportunity to live and learn about another country and its research environment. I am grateful to the people I meet who enriched my journey.

4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
I would integrate more presentations and scientific discussions at my local University. One of mine wishes is that a Marie Curie Fellowship implement free courses of the local language. It helps to integrate in the new environment and the research would benefit as well.

5. How did the PEARRL network impact your doctoral experience?
I enjoyed collaborating within PEARRL on different topics and broader my knowledge in other fields of pharmaceutical sciences.
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Interview with ESR10, Patrick O'Dwyer

6/15/2020

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Patrick O'Dwyer (ESR10) has recently successfully defended his PhD. We held a short interview with Patrick to find out more on his project and plans for the future. We would like to congratulate Patrick and wish him all the best.
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1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research project focused on the development of small-scale lab tests to replicate the transfer of a medicine from the stomach to the small intestine. Many of the new chemical entities and drug formulations in the development pipelines are sensitive to this change of environment, resulting in supersaturation and precipitation of drug in the intestine. As this supersaturation and precipitation can greatly affect the oral absorption of the drug, it is critical to understand this behaviour at an early stage of development. In early stage development, very limited quantities of drug are available, thus necessitating the use of small-scale methods. The tests developed as part of my work show the effect of the transfer from gastric to intestinal conditions using only small quantities of drug. In addition, we have incorporated the results from our lab-based tests into computational modelling software to gain a better understanding of the oral absorption prospects of a drug / drug product .         


2. What impact does your research project and your outcomes have?
The tests developed as part of this work will be hugely beneficial to industry during the drug development process. Obtaining relevant information at an early stage of development facilitates a more efficient development process. This efficiency can save time and money for industry, with a knock-on benefit of enabling earlier access of patients to new medicines. By incorporating results from our labs tests into computer models, a better understanding of the factors affecting the performance of the drug / drug product can be achieved. This combination of lab tests with computer modelling should help to reduce the number of animal and human trials required in the future, highly beneficial from both a resource and ethical point of view.

3. What were your personal highlights over the course of your research project?
The PEARRLs of wisdom weeks were hugely enjoyable and a particular highlight during my PhD. It was a great experience to present work to experts in the field, with an added benefit of getting very constructive feedback to improve your research. In addition, it was a great opportunity to build your network and establish collaborations between all the projects. Several training workshops were also included as part of the weeks and they covered very valuable topics such as scientific writing skills, presentation skills and commercialisation, just to mention a few!

4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
I think the secondments were a brilliant part of the PEARRL project. I hugely enjoyed my secondment at the European Medicines Agency. It was great to experience the regulatory environment and it really opened my eyes to the work of the regulators. My academic secondment to the National and Kapodistrian University of Athens was also hugely beneficial by learning new laboratory techniques and running many experiments.

5. How did the PEARRL network impact your doctoral experience?
The PEARRL network hugely benefited my doctoral experience. From a professional point of view, it opened up many opportunities for collaboration, drawing on expertise from all parties. In addition, it was brilliant to regularly receive feedback on my work from experts across Europe. From personal point of view, I have gained many close friends from the network (giving me a great excuse to travel across Europe to visit them all!!)  

6. What are your plans for the future?
I have recently started a position as Lecturer in Pharmaceutics in University College Cork. This will allow me to continue to my research from the project and lead innovative research in the future.


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Niklas Köhl (ESR1) successfully defends his PhD

6/3/2020

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We are happy to congratulate Niklas Köhl (ESR1) on successfully defending his PhD. We have also interviewed Niklas about his research project, his time within PEARRL and plans for the future.
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1. What has your research project focused on and what are your key results and innovations coming from your research project?
My research focused on the development of lipid-based formulations for new emerging drug types to improve oral bioavailability. We focused on poorly lipid and aqueous soluble drugs and the development of different lipid based formulation types for these compounds. Such an approach allows to explore the benefits and risks associated with the different lipid-based formulations in order to guide the formulation development of low lipid soluble compounds within the field of lipid-based formulations.
As a result of this project, we developed various lipid-based formulations, which are applicable from very early phases of the drug product development process to formulations that can be marketed. Furthermore, we demonstrated that lipid-based formulations have the ability to improve oral bioavailability for low lipid soluble drugs.  
 
2. What impact does your research project and your outcomes have?
Lipid-based formulations is a rarely used formulation approach due to a low solubility in lipid excipients of many new drugs. Our research informed the scientific community that lipid-based formulations are a viable approach for drugs that show a limited lipid solubility. Therefore, potentially more drugs can be formulated as a lipid-based formulation to improve oral bioavailability from very early phases to late phases as well as the commercial stage of drug product development. The wider application of lipid-based formulations potentially increases patient compliance and results in improved drug products on the market.
 
3. What were your personal highlights over the course of your research project?
A key highlight was being part of such a European wide network that combines academia, industry and regulatory authorities. Throughout my research project, it was great to get insights into all three areas in the context of pharmaceutical development. Moreover, I enjoyed collaborating with fellow scientists and project partners, which fostered great science and allowed me to acquire a unique set of skills and encouraged my personal development. Especially, events such as the PEARRL weeks of wisdom stimulated such collaborations within, but also with scientists outside of PEARRL.
 
4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
Besides transferable skills training such as scientific writing and presentation training, I think within the pharmaceutical doctoral programmes training on regulatory topics/requirements are beneficial.
 
5. How did the PEARRL network impact your doctoral experience?
The training within PEARRL gave me the opportunity to look beyond my own research topic and allowed me to broaden my knowledge in different research areas and acquire an unique set of skills. In addition, I had great support, resources and manifold possibilities to collaborate which lead to great scientific results. Also, the relocation to Ireland was great to learn about a different culture and meet new people.
 
6. What are your plans for the future?
After PEARRL, I am going to start at Janssen Pharmaceutica in the area of formulation development, which matches the work I have been doing during my PhD.

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Georgia Tsakiridou (ESR4) successfully defends her PhD and gives an interview!

5/29/2020

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Congratulations to Georgia Tsakiridou (ESR4) which after successfully defending her thesis via online meeting, has received her PhD. Find below a short interview with Georgia Tsakiridou about PEARRL and her future goals.
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1. What has your research project focused on and what are your key results and innovations coming from your research project?
Nowadays, more and more active pharmaceutical ingredients (APIs) present solubility problems. A common formulation choice for these APIs is the formulation of ASDs, where the API in the amorphous state is dispersed in a polymeric carrier. However, the development of these formulations is often hindered by the possible instability of the amorphous API, that tends to revert to its crystalline state during manufacturing and storage, and  by our difficulty in predicting adequately their in vivo behavior. With this work we introduced a workflow that enables the acceleration of the development of ASDs in a step by step manner, using Tacrolimus as a model API. First we introduced a novel rheology based method to the field of ASDs which enables the selection of appropriate polymers for the preparation of stable and successful ASDs, by connecting the viscosity of the API-polymer solutions to the miscibility of API and polymer, as it has been reported that API-polymer miscibility is crucial for ASD stability. The polymers deemed most appropriate were used in order to prepare tacrolimus ASDs via the Spray drying method in a design of experiment approach. Stability experiments showed that amorphous tacrolimus remained stable even 6 months after preparation, further verifying the importance of the rheology-based method. On the second front of predicting the in vivo behavior of ASDs we investigated the usefulness of the apparatus IV, using biorelevant media that mimic the conditions in the gastrointestinal lumen, in predicting the in vivo performance of 2 commercial tacrolimus formulations and one test formulation prepared based on the output of the rheology based method. It was revealed that the dissolution data from the apparatus IV showed a good predictive ability for the initial exposure of these formulations in vivo, which underlines the need to move towards more biorelevant set-ups and apparatuses that better mimic the physiological conditions in order to better capture the in vivo performance of ASDs.

2. What impact does your research project and your outcomes have (in your field of research, in drug development, any benefits for the general public etc.)?
ASDs are a very important part of drug development, as a formulation choice, because they provide many advantages. However, their commercial use is not as pronounced as it could be due to the bottlenecks in their development. In my opinion, this work provided a systemic way of dealing with these bottlenecks from early formulation choices to the in vivo performance of ASDs. Undoubtedly, this work shows many limitations but it could provide a framework for the potential acceleration of ASDs development, especially for APIs with similar characteristics to tacrolimus.

3. What were your personal highlights over the course of your research project (training, results, awards, networking etc.)?
It is definitely a combination of all those but I also distinguish the effect of the “PEARRL people” in this experience. It was a great opportunity to be able to converse with leaders in the field of pharmaceutics, who approached each of us with a truly inspiring love for teaching and science. It was also a wonderful experience to meet and collaborate with the other ESRs of the PEARRL network which was a great learning environment.

4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
The importance of Physiologically based pharmacokinetic (PBPK) modelling is constantly being proven in the field of Pharmaceutics. Consequently, the fact that the PEARRL network gave me the opportunity to attend related workshops and familiarize with the topic was a great training experience that I believe would benefit other PhD candidates. Moreover, another great learning experience was the three months I spend in the Greek regulatory agency for medicines, as it provided an inside view of the work being done in the regulatory agencies, which is another aspect of the drug development process.

5. How did the PEARRL network impact your doctoral experience?
The fact that I was a member of the PEARRL network greatly affected my doctoral experience, as the sense of a team was very prominent from the beginning, not only due to the collaboration opportunities and monthly virtual meetings and annual conferences, but also due to the sense of moving towards the common goal of providing better medicine in a safer manner to the public. Moreover, another thing that greatly impacted my experience was the mobility that was introduced in the PEARRL program that allowed me to experience different working environments in academia, industry and the regulatory sector.

6. What are your plans for the future?
My future plans include working in the pharmaceutical sector at Pharmathen S/A in the department of Clinical Operations, where I can apply many skills acquired during my PhD, potentially including PBPK modelling. Moreover, my future plans, also, include raising a family.
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An interview with Felix Ditzinger (ESR2)

5/5/2020

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Felix Ditzinger (ESR2) has recently received his PhD. We would like to congratulate Felix on successfully defending his PhD and have held a short interview to hear about his experience in PEARRL.

1. What has your research project focused on and what are your key results and innovations coming from your research project?
The key aspect of my research was to explore new excipient combinations for hot melt extrusion (HME). We focussed on interacting small molecular additives in combination with established polymers to change the physico-chemical properties for a more feasible processing in HME. Such an approach should lead to new modified polymeric matrices, which broadens the selection of carriers for the development of an amorphous solid dispersion.
As a result of this project, we were able to develop various modified polymeric matrices and have demonstrated  the beneficial properties with regards to stability of the amorphous form, amount and duration of supersaturation in biorelevant media as well as downstream processing capabilities. Moreover, we could show in an in vivo rat study that the matrices are capable of improving the oral absorption of a poorly water-soluble drugs.
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2. What impact does your research project and your outcomes have (in your field of research, in drug development, any benefits for the general public etc.)?
The concept of my research, which includes the combination of small molecular additives with polymeric compounds, can be applied in the development of new drug products, especially if a feasible carrier cannot be found. In brief, this concept has the potential to enable more drugs to be formulated as an amorphous solid dispersion and consequently can lead to improved drug products on the market.

3. What were your personal highlights over the course of your research project (training, results, awards, networking etc.)?
In my opinion, the personal highlights of this project are not awards or only the results. The personal benefit of my research project lies also in the collaboration with my fellow ESRs and other partners. Through such a network, personal growth and the capability to work in a team-orientated environment are encouraged, which should be the focus in such a network.


4. Are there any elements of the training you received that you find should be integrated in local doctoral programmes?
The scientific writing training and the presentation training, I received during the Wisdom Weeks should be integrated in more doctoral programs, since those two things are a key aspect to success of every PhD.

5. How did the PEARRL network impact your doctoral experience?
Through my participation in the PEARRL network, I got the opportunity to collaborate with many fellow scientist and other people, which provided significant scientific results. Moreover, on the personal side I learned to organize projects with fellow ESRs, who were not located at my university. In line with the growth in social skills throughout the project, I was encouraged to become a more team-oriented researcher.

6. What are your plans for the future?
In the future, I am going to be working in the pharmaceutical industry at Roche, which gives me the opportunity to apply the capabilities I learned during my years in the PEARRL network. My working field will be the formulation development, which fits perfectly to the field I did my PhD in.
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This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 674909.
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