Simon Bock is a Pharmacist by training and PhD student at the Department of Pharmaceutics and Biopharmaceutics at Kiel University, Germany. His research focuses on DPI formulation development through implementation of Additive Manufacturing technologies in pharmaceutical processes. His PhD project comprises the evaluation of complex dispersing aids and unconventional carrier geometries in dry powder inhalation. Prior to his academic research, he completed his studies of pharmacy at the Technical University of Braunschweig, Germany, in 2016. After graduation, he worked for several local pharmacies in Hamburg and the Frankfurt area, Germany. In addition, he gained first experiences in the pharmaceutical industry working in the quality management unit of Sanofi Germany. Since April 2018, he has been employed as a research associate in the working group of Prof. Regina Scherließ at the Institute of Pharmacy in Kiel, Germany. Besides research on particle engineering of DPI formulations he has been responsible for the practical academic teaching to undergraduates. To present his scientific findings he was previously selected for giving several live talks including the NordicPOP conferences in Oslo in 2019 and Copenhagen in 2020.

Project summary

My PhD project entitled Application of additive manufacturing in the development of DPI formulations has two objectives: On the one hand, the application of additive manufacturing (AM) processes to fabricate complex, uniform carrier geometries. On the other hand, the development and production of accessories with intricate details to improve dispersion of dry powder formulations. For such formulations, API particles are oftentimes blended with coarse carrier particles. The production process of the standard carrier, irregularly shaped lactose particles, implies a high degree of inter-particle variability, which can potentially lead to dose-to-dose variations. Despite the advantages of processability and dosability, perfect spheres may be similarly unsuitable as carriers with regards drug loading capacity, surface properties, fluidisability, etc. It remains unclear which specific carrier geometry and size is most suitable. The production of non-spherical and uniform particles on a microscale to systematically assess the influence of geometry and size has not been technically possible in the past.
The aim of the project is thus to systematically assess the influence of both characteristics by high-precision fabrication of uniform particles. The focus is on how such techniques could contribute to a better understanding of fundamental processes that occur during inhalation of DPI formulations. Small-scale manufacturing and processing enable the production and evaluation of innovative interactive blends with tailored API capacity and delivery performance. As a hypothetical result, it might be feasible in the future to make active substances available for inhalation therapy that hitherto could only be administered to the lungs in insufficient or uncontrolled doses by specifically altering the carriers.
In addition to the production of customised carriers as such, my project includes the investigation of relatively large dispersing aids as free-levitating accessories in DPI devices. It remains unclear to what extend such accessories can influence the dispersion of powder formulations within an inhaler. Since the deagglomeration of formulation components is influenced by particle-particle interactions, dispersing aids could provide additional kinetic energy to overcome particle adhesion forces. This might result in a better aerosolisation and thus higher dispersing efficiency. The magnitude and intensity of energy input might be related to the behaviour of the object in the fluid within the device, which is influenced by its’ morphology and size. Furthermore, surface structure and roughness of such aids are considered to influence the particle interactions and thus the dispersing capacity. Only state-of-the-art manufacturing techniques, which are challenging and costly, can guarantee accurate control of such properties. Hence, using appropriate fabrication techniques allow a better statement of the actual impact of various types of dispersing aids.

Career Development Award Proposal

As a pharmacist by training and a formulation scientist in the current position, the combination of classic pharmaceutics with AM techniques offers a broad widening of my personal and professional horizon.
The urge to wander off the beaten track has always been part of my professional lifetime. In 2016, I finished my studies of pharmacy at Technische Universität Braunschweig, Germany, with the 2nd state examination. During my studies I spent some time at the University of Agder, Norway, with a non-pharmaceutical curriculum. Furthermore, voluntary internships at Boehringer Ingelheim and Bayer Healthcare allowed me to gain insights in the pharmaceutical industry. After my 2nd state examination, I spent the following practical year in a pharmacy and at the pharmaceutical company Sanofi. Having been licensed as a pharmacist in 2017, I worked in the Frankfurt area in various pharmacies but also on the development of a smartphone app for pharmaceutical professionals. With work experience from pharmacies, the pharmaceutical industry and other ventures, the research related to respiratory drug delivery intrigued me the most. It stroke me, that this particular branch of medicine and pharmaceutics, respectively, is still relatively small and that there could be a lot to explore. In addition, I have found that my personal interest lies mainly in research and development. Therefore, I applied as a PhD student in the research group of Prof. Regina Scherließ at the Department of Pharmaceutics and Biopharmaceutics at Kiel University, whose research activities already covered this topic for many years.
Since April 2018, academic teaching and student supervision is an essential part of my current work at Kiel University. The content covered in lectures and practical courses comprises a wide range of topics related to pharmaceutics and biopharmaceutics: from solid, liquid and sterile dosage forms to inhalatives and transdermal application systems etc. To explain the need of established but also of innovative dosage forms is a crucial part of the lectures. In addition to the teaching as such, for the time being I am responsible for the overall organisation and scheduling of an extensive lab class on pharmaceutics. It involves the transformation from analogue to digital teaching, which became necessary due to the current pandemic. This digitalisation of academia offers novel ways of communication and collaboration. As an additional effect, the potential of computational tools for research and development in all aspects of pharmaceutics gets increasingly into focus.
On top of the daily routine of academic teaching, to provide insights into research to undergraduates means a lot to me. In 2019, I initiated and was responsible for an internship in the Department of Pharmaceutics and Biopharmaceutics for a student from the United States of America. With the student being a chemical engineer, the internship was characterized by a lively exchange of different scientific perspectives from both parties. This period strengthened my conviction, that interdisciplinarity is always beneficial in research. I am convinced, that to wander off the beaten tracks can generally be worth it.
From the very beginning of my doctorate, I have been working on particle engineering of dry powder inhalation carriers in interactive blends. Initially, I worked with basic operations such as carrier coating to investigate the effect of surface modification on the aerodynamic performance. In this work package, model MCC-carriers with relatively consistent sphericity and narrow particle size distribution were covered with several amino acids in a fluidised bed coating process. Subsequently, the effect of both the particle size and the coating of the carrier on emitted dose and fine particle fraction of API were investigated. The diversity and magnitude of variability in production and processing of carriers has hindered a systematic study of isolated, individual parameters ever since. In the framework of this work package, the question arose whether novel technologies could provide new investigatory concepts. As a result of attending the NordicPOP conference in January 2019, at which I was accepted to give a live talk on my research, an opportunity for a scientific collaboration with the institute of pharmacy in Oslo, Norway, came up. Specifically, a temporary stay in Prof. Ingunn Tho's research group was arranged. The aim of this visit was to work out how 3D printing (3DP) could generally be useful for the development of orally inhaled and nasal drug products.
During that two-week stay in March 2019, I was kindly introduced to the principles of AM with the help of Eric Kissi, Postdoctoral Research Fellow at the University of Oslo. Hands-on experiments with standard equipment supplemented my theoretical knowledge about 3DP. With two undergraduates, who accompanied me for one week, plenty of tools and prototypes were manufactured to acquire advanced knowledge. From digital design, slicing, preparation of filament or resin to printing and post-processing, the variability of 3DP workflows is unimaginably high. Therefore, and in view of the following work package, I decided to focus on refining a handful of prototypes. These prototypes were then used as accessories in DPI formulations. Particularly, several relatively large prints with well-defined shape were inserted into the main chamber of a Twister® device. The aim of this insertion was to proof, if such free-levitating structures provide additional dispersing effects. Proof of concept on whether these prints could be used as dispersing aids was first mentioned in an abstract submitted for the DDL 2019 conference. This concept and its preliminary results matured not only into the central theme of my doctoral research but also into a submission for a European patent.
The task now is to further evaluate the optimal geometry and size of a dispersing aid. Based on the prototypes previously used, a handful of geometries with intricate details and much higher complexity were selected for three-dimensional printing. Once these objects will each be fabricated in different sizes with highest resolution, the influence of the resulting products on the DPI performance can be investigated. For this purpose, the aids will be inserted into an inhaler device together with interactive powder blends or soft pellet formulations, using different APIs in each case. In the course of an aerodynamic assessment, the effect on the dispersion performance can then be analysed.
The considerable degrees of freedom of AM in terms of particle morphology and manufacturing allow new routes to tackle long-standing challenges. This technology is still considered to be in its infancy. However, with the progress made in the recent past, the applicability and accessibility are steadily increasing. At this point in time, the first use of additively manufactured, extraordinarily complex DPI carriers in a size of a few micrometres is within reach. Nevertheless, sound decision-making for the allocation of finances, software, equipment, and personnel is imperative for further progress in this area.
Due to the need to fabricate objects with intricate details in high resolution, access to suitable manufacturing technologies is a major bottleneck. Therefore, the progress of the current work package is heavily dependent on financial and technical support. In the long term, numerical simulations complemented with formulation-specific parameters and coupled with deep-learning algorithms could yield a continuous optimisation of both carrier and dispersing aid designs. With technologies capable of producing such geometries, access to an in-depth study of particle characteristics and behaviour appears attainable in the future.
It took two years of theoretic, hands-on and collaborative experience in 3DP to reach the current state. Technology for manufacturing of complex designs down to a few microns is now available. With the knowledge acquired in the past, the DDL Career Development Grant would open a new chapter of interdisciplinarity in my personal and professional career as a scientist. Financial support could help to give general insights how AM processes can potentially be applied in respiratory sciences. My personal goal is to elaborate explanations of fundamental mechanisms in DPI formulations and to raise new scientific questions in the intersect of formulation development and AM. This grant would provide access to state-of-the-art printing technologies, enable collection and validation of data and accelerate the research process.
My intention is to publish a comprehensive scientific paper outlining initial explorations of the potential capabilities of complex dispersing aids and unconventional carrier geometries in dry powder inhalation. Since the use of the corresponding fabrication technologies is still unexplored in many respects, it can be expected that research in this area will continue in both academic and institutional settings. Contributing to the expansion of this emerging field of research is my personal goal. I would be delighted if this work would eventually culminate in a presentation to an international auditorium of aerosol scientists. The Career Development Grant could substantially support this project that would mark a cornerstone of interdisciplinarity in my personal career in the field of drug delivery to the lungs