Coriolis Scientist wins Prize for PhD Thesis about Freeze-drying
Ghent University awards Dr. Brecht Vanbillemont
The Faculty of Pharmaceutical Sciences at the Ghent University in Belgium has just awarded the best PhD theses of the academic year 2019/2020. Coriolis scientist Dr. Brecht Vanbillemont is among the laureates with his thesis on “Development and evaluation of next-generation pharmaceutical freeze-drying technologies”.
The entire Coriolis team congratulates Brecht to this great achievement! We are happy to have him on-board and are looking forward to developing many robust lyophilization processes together.
![Ghent University awards Dr. Brecht Vanbillemont](/sites/default/files/styles/w800/public/images/phdprize.png?itok=2bRHZHUy)
Image of the virtual award ceremony
Abstract of the PhD Thesis
The pharmaceutical industry of the 21st century is facing some challenges due to a changing landscape. With the rise of biopharmaceuticals, product development is becoming more advanced and research more costly. Profound scientific process understanding is promoted and could eventually lead to a high level of automatization and supervisory process control. Process analytical technologies are essential in establishing that goal. Another trend is the transition to continuous processing. These next-generation technologies are developed and evaluated in the thesis in the field of pharmaceutical freeze-drying. One major research section of the thesis focuses on research concerning the freeze-drying of parental unit doss. At first a high-level supervisory control and optimization algorithm was successfully developed and verified for batch freeze-dryer apparatus that are common in industry. This next-generation technology is fully compatible with the Quality-by-Design guidelines and allows for a more economical operation of the process while guaranteeing the product quality. Next, process knowledge on the continuous manufacturing of parenteral vials via spin-freeze-drying was deepened. More specifically, the impact of the different spin-freeze-drying process phases on the stability of bio-pharmaceutical formulations was investigated. The research showed that the destabilization mechanisms and their extend were similar in comparison to the current batch freeze-drying methods. At last, an X-ray micro-computed tomography (μCT) based analytical technology was developed, to in-situ image the primary drying phase of spin-frozen vials. This allowed for a mechanistic unravelling of the mass balance of sublimation. The other major research section targeted orally disintegrating tablets (ODTs) manufactured by freeze-drying. To develop the next-generation technologies, a thorough assessment of these tablets were necessary. A wide range of specific characterization techniques was tested and where needed adjusted for the needs of ODTs. Later, a systematic evaluation was done on the results to learn more on the functionality of these tablets. Next, a successful formulation platform was developed with polyvinyl acetate as the polymeric binder of lyophilized ODTs. Both a low-dose and high-dose formulation were optimized using design of experiments (DoE) methodology. Finally, a design of a continuous manufacturing technology for ODTs was proposed. A Proof-of-Concept (PoC) apparatus was developed and evaluated. The experimental work on the PoC proved that thermoelectric coolers were suitable for use in the continuous SMART mold concept. Moreover, a heat flux monitoring and process control was proposed and proved successful in optimizing the primary drying process in the SMART mold. At last, a model-based design of a technical prototype for continuous manufacturing of ODTs was elaborated with the help of uncertainty analysis of mechanistic models on essential process dynamics.