Background

The Institute of Process and Particle Engineering is a world leader in the development of pharmaceutical products and processes.

In this context, we are offering a paid master thesis where the student is employed at an external company.

The goal of the master thesis is to create the basis for product development, focusing on a novel drug delivery system where the medicine is contained in a flavored gel, either as solution, emulsion or suspension. Drug delivery occurs via breaking a seal of a snap-package and sucking out the flavored gel. Target patient populations includes:

• Geriatric patients (frail & old patients)
• Pediatric patients (kids)
• Emergency applications

Tasks

• Literature study on competitor products and patent situation
• List of the 20-30 most important medicines for the three target populations and corresponding biopharmaceutical classification
• Research on formulation strategies (solutions, emulsions, suspension) with sufficient stability
• Selection of 3 model APIs (different categories) and formulation of the gels
• Stability testing under stress conditions

Requirements

• Background in pharmaceutical sciences, pharmaceutical engineering or medicines
• Student in pharmacy, pharmaceutical engineering, chemical engineering or related

What we offer:

• Integration in an internationally leading team
• Opportunity to be part of a commercialization project
• Paid thesis

Start: Spring 2021

Contact: Univ.-Prof. Dr. Johannes Khinast, khinastnoSpam@tugraz.at

Background

Continuous flow synthesis has recently emerged as the new paradigm for the manufacturing of active pharmaceutical ingredients (APIs). Many benefits come with implementing continuous processes, such as increased throughput, constant product quality, the possibility of controlling and automating the process, increased safety and waste reduction. Continuous flow processes are also widely considered a valid platform where to implement and test new technologies that can change  the way fine chemicals are traditionally manufactured. Lately, there has been increasing interest in the application of biocatalysts as a tool for synthetic chemistry, since it is considered a very promising  and greener alternative to conventional catalysts, which are mostly metal-based. Enzymes have many advantages, such as low toxicity and environmental impact, high activity in mild conditions, and high selectivity. Therefore, the possibility of exploiting the advantages of continuous flow synthesis as well as biocatalysis is very attractive for both researchers and industry. However, still a lot of work needs to be done to increase the feasibility of biocatalysts and to design continuous flow biocatalytic processes that can be industrially competitive.

Figure 1 – Generic scheme of a multistep (bio)catalytic process

The aim of this project is to develop a process for multistep (bio)catalytic cascade reactions for the production of APIs in continuous flow. The process can be flexible and feature different modules: reaction modules that can host packed bed reactors filled with the immobilized enzymes or catalyst, as well as modules for other unit operations (e.g. heating/cooling, mixing, extraction). A great part of the work will be dedicated to identify an optimal immobilization strategy onto innovative supports (e.g. 3D printed, see Figure 2).  The possible challenges include: finding an optimum immobilization protocol that minimizes leaching and optimizes the stability of the enzymes; the choice of an optimal solvent compatible with multiple reaction steps; the possible interaction of by-products within the system. To increase process understanding and efficiency, the possibility of implementing process analytical tools, such as inline sensors for real-time analyses, will be explored as well.

Figure 2 -  CAD design of a honeycomb type of  support structure

Tasks

• Literature study on industrial biocatalysis in continuous flow and enzyme immobilization
• Study of the enzymatic reaction kinetics in batch
• Design of an adequate continuous process
• Optimization of the reaction/process conditions
• Implementation of real-time analytics (e.g. UV-vis probes)

Requirements

• Background in chemical engineering, chemistry or biotechnology
• Interest in the above mentioned fields
• Basic lab work experience

What we offer:

• Integration in an internationally leading institute (IPPT) of TU Graz
• Support from the CoSy Pro Team
• Paid thesis (in case of the Masters’ thesis)

Start
At any time

Contact:
Dipl. Ing. Dott.ssa Alessia Valotta
valottanoSpam@tugraz.at - +43 316 873 - 30428

Assoc. Prof. Dipl.-Ing. Dr.techn. Heidrun Gruber-Wölfler
woelflernoSpam@tugraz.at