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Master Thesis – Characterization and optimization of a 3D printed continuous crystallizer for pharmaceutical applications

Background:

Crystallization is one of the most important unit operations in the production of active pharmaceutical ingredients (APIs) in a solid form. It defines product properties like purity, crystalline structure, crystal size and the crystal size distribution, which is especially important for further downstream operations like filtration and formulation of pharmaceuticals. Because of lower production volumes in the pharmaceutical industry compared to industrial inorganic salt production, the development of continuous processes for the production of certain APIs was not profitable in the pharmaceutical industry in the last decades.

Nevertheless, companies are now investing into the development of continuous processes for synthesis and also crystallization, since a constant quality can be ensured and no service time in between production batches is necessary. Therefore, crystallizers and crystallization processes for continuous applications have to be developed.

The aim of this master thesis is to design and characterize a continuous crystallizer by exploiting recent advances that have been accomplished in the field of additive manufacturing (3D-printing). Based on the working principle of an OSLO-type crystallizer, this technique will facilitate realizing a modular setup. Thereby, rapid replacement of parts of the reactor is feasible, allowing to analyze their influence on the overall behavior. This strategy aims to provide previously unattainable insights into the behavior of continuous crystallizers. The main challenge of the thesis will be the characterization of the current crystallizer using simple model systems. In a possible second step, alternative designs should be evaluated and produced, using additive manufacturing, to optimize the overall performance of the crystallizer.

Figure 1: Current Design of the OSLO type crystallizer.

Tasks:

Literature study on crystallization / especially continuous crystallization
Simple crystallization experiments and evaluation of the results (Particle size distribution, concentration measurements [HPLC, optical methods], Residence time distribution measurements)
CAD drawing and 3D printing

Requirements:

Background in chemical engineering, chemistry or related studies
Interest in the above mentioned fields
Basic lab work experience
NO PRIOR KNOWLEDGE in CAD or 3D printing required
Good work ethic

What we offer:

Integration in a research project supported by an industrial partner
Support from the CoSy Pro Team
Paid Thesis
Experience in an upcoming field of greatest importance
Start: As soon as possible.

Contact:

Dipl.-Ing. Nys Nico, BSc
nico.nysnoSpam@tugraz.at - Tel.: +4331687330438

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

Paid Master’s Thesis – Molecular Dynamics Simulations of Transport in Polymers

Background
Polymers are used in the electrical industry to insulate devices. Especially in corrosive atmospheres the investigation of the degradation of these polymers and the protected devices is of vital importance to increase their longevity. One main influence is the diffusion of corrosive substances through the protective layer of a device. In recent years as computational power became cheaper, using molecular dynamics simulations to quantify transport properties of polymers became more commonly used.

In this thesis molecular dynamics (MD) simulations should be used to quantify the transport processes of different penetrator molecules in polymers. Investigations regarding the polymer’s chain-length, the degree of cross-linking, as well as the charge of the penetrator molecules under different environmental conditions should be conducted.

Tasks

Running and analyzing molecular dynamics simulations of polymers
Investigation of physical properties of polymers

Requirements

Solid background in chemical engineering
Knowledge of Matlab or Python
Enthusiasm to work with theories, software, and computer algorithms
Interest and enthusiasm for performing simulation on supercomputers

Work on the thesis is paid (6 months), and we offer office space, computers, simulation software and expertise, as well as integration to a highly-relevant research project

Contact
Dr. Stefan Radl (radlnoSpam@tugraz.at; 0680 12 22 168)
Dipl.-Ing. Philipp Mayr, BSc. (philipp.mayrnoSpam@tugraz.at)

Paid Master’s Thesis – Optimizing Chemical Reactions via Machine Learning

Background

The optimization of chemical reactions has always been a critical step in both industrial, as well as laboratory scale processes. Recent advances in the field of continuous flow synthesis have led to the possibility of running automated chemical reactions with minimal human intervention. Combining these automated reactions with machine learning optimization algorithms offers exciting new possibilities in this regard.

The goal of this project is to compare different algorithms by letting them optimize several chemical reactions in continuous flow. For this, the reactions have to be tested generally in batch, and then translated into an automated continuous reaction setup, which will run experiments automatically. The automation and optimization software is coded in Python.

Tasks

Literature study on prominent chemical reaction steps relevant in pharmaceutical engineering
Testing of the chosen chemical reactions in batch
Translation of batch experiments into continuous flow
Automation of the developed continuous flow setup
Optimization of the reactions via different algorithms

Requirements

Background in chemical engineering, chemistry or similar
Basic laboratory work experience
Interest in the above-mentioned topics
No programming knowledge needed (but being interested is advantageous)

Contact

Dipl. Ing. Sebastian Soritz
s.soritznoSpam@tugraz.at - +43 316 873 - 30409

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

Paid Master Thesis or Student Job - Developing a Novel Drug Delivery System for Special Patients

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

Paid Master Thesis or student job: Comparing Bioreactors with different scales and/or geometries

Background

The Institute of Process and Particle Engineering is a world leader in the development of simulation tools for industrial-scale bioprocessing units, funded by the Spin-Off Fellowship Program of the FFG. For example, our current code can model processes in large-scale bioreactors, up to 200m³ .
We are therefore offering a student job with the possibility to do a master thesis with the goal of creating a comparison algorithm for bioreactors. The objective is to find the influencing factors that determine the productivity difference between reactors. This should be done by comparing reactors of different scales and for reactors at the same scale but different geometry and should aid scale up or process transfer processes in the industry.

Tasks

Literature study on available influencing factors or comparison concepts for the production in bioreactors using cells or microorganisms
Propose an algorithm for the comparison of reactors
Do scale ups or process transfer virtually

Requirements

Background in biotechnology, biochemistry, molecular microbiology or similar
Being familiar with industrial production in bioreactors

What we offer:

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

Start: Fall 2020

Contact
Dr. Christian Witz
0316 873 30416
christian.witznoSpam@tugraz.at

Continuous Cooling Crystallization

Background

For this construction thesis we are looking for a student to design a water bath made of stainless steel for continuous cooling crystallization in a tubular reactor (plug flow crystallizer).

Using such a tubular crystallizer the continuous cooling crystallization process should be carried out in two water baths of different temperature. Each water bath has separate glass inserts which enable the visual observation of the crystallization process within the tubes via a high speed camera. To achieve high resolution images a backlight source e.g. a LED panel in addition to the camera is necessary. Due to the reflection of the water inside the bath the distance between the backlight and the camera should be as short as possible. To keep the tube cycles uniformly immersed and to guide them special tube mountings are also required.

Tasks Waterbaths Setup

To design a water bath of stainless steel with glass inserts for the image-based observation of a continuous cooling crystallization within a transparent tubular crystallizer.
To make a selection of necessary materials and equipment and process the orders
Image-based monitoring and observation of crystal segments via high speed camera and backlight
Doing some final experiments to demonstrate the applicability of the two water baths for visual investigations.

Requirements

Background in chemical / pharmaceutical engineering or chemistry
Basic experience in working with CAD drawing desirable
Basic experience in lab work

What we offer

Integration in an internationally leading team

Contact

Dipl.-Ing. Alexander Meister, BSc
Inffeldgasse 13 / III, 8010 Graz
alexander.meisternoSpam@tugraz.at

PAID MASTER’S THESIS: Influence of powder composition on macroscopic powder properties

To dedicated students who are interested in the pharmaceutical field (i.e. students of chemical engineering, pharmaceutical engineering, biomedical engineering, pharmacy, or related disciplines), we offer an opportunity to write a paid Master’s thesis.

OBJECTIVE:
Powder processing steps, such as feeding and mixing, are critical in many industries, including the pharmaceutical industry. For example, within a continuous tablet manufacturing environment, powder feeding impacts functionality and quality of the final product. For the rational design of such operations the powder properties need to be known, including the particle size distribution, bulk (poured) and tapped density, flowability, compressibility, electrostatic chargeability and tendency to segregate.

Thus, the development of solid dosage forms and the associated manufacturing processes requires a good understanding of the relationship between powder composition and the properties of the powder.

WITHIN THE FRAMEWORK OF THIS MASTER’S THESIS WE OFFER THE FOLLOWING:

Extensive participation in a top-level and industrially relevant research project in an international environment Supervised training in the task
Assistance of experienced staff with the implementation of innovative ideas
Access to highly modern infrastructure on campus of Graz University of Technology
Assistance with the publication of results Adequate compensation and opportunities for personal and professional development

FINANCING:
Compensation on the basis of a service contract

If you are interested in writing your thesis at the process and particle engineering institute of TUGraz, please contact us indicating the reference number. Candidates will be selected on a competitive basis and will be selected without regard to sex, race or nationality.

Contact: Sara Fathollahi (sara.fathollahinoSpam@tugraz.at, 0316 873 30938)