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DTU Studieprojekt - Precipitation mixing and scale up down

Danmarks Tekniske Universitet (DTU)

Virksom - a-kasse og faglig organisation for selvstændige


Precipitation mixing and scale up down

Udbyder
Vejleder
Sted
København og omegn
Precipitation in the pharmaceutical sector refers to the rapid formation of a sparingly soluble amorphous, semi-crystalline or crystalline solid phase from solution. The technique is rather poorly understood when compared with crystallization due to the spontaneous and rapid way in which nucleation, growth, and secondary phenomena such as agglomeration occurs together. In many cases, these processes are difficult to separate and investigate independently and mechanistically (Karpiński & Bałdyga, 2019).

While many decades of scientific and engineering endeavor have been invested in the development and understanding of crystallization, such as the prediction of solubility with population balance modelling, there is a significant gap in our understanding of precipitation processes.

In precipitation the final particle size distribution and its amenability to e.g. filtration, drying and further downstream processing is influenced by:

· the initial solvent composition,

· temperature and other physical properties,

· the rate or position of precipitant addition and the ensuing mixing conditions (i.e. macro, meso and micro mixing times),

· the rates of nucleation, growth and agglomeration of the developing solid phase.

Often we end up with complex models that include numerous fitted terms, for example, for “induction time” and “birth rates” (Zauner & Jones, 2000). As such there are a range of approaches to modelling, design, operation and optimization of precipitation reactors (Baḱldyga, Podgórska, & Pohorecki, 1995, Bałdyga, 2016).

LEO Pharma’s Global MSAT team is interested in learning more about practical and theoretical approaches to the characterization of precipitation processes, and how they may be successfully scaled up and down. As such, we propose an MSc project where the student is expected to initially update us regarding the present state of the art on precipitation, and characterize and verify how one of our seemingly simple precipitation processes obey the existing rules. The student together with the supervisors will then need to demonstrate some creativity to discover good scale up or scale down rules for reproducing a desired precipitation process in laboratory or production scale.

LEO has well equipped laboratories as well as production scale equipment and is a short bus ride from DTU. DTU has some of its own facilities but also has considerable expertise in modelling and simulation, including CFD. The student will have considerable autonomy in managing the required time spent at the different sites, the design of any experiments (DoE), and the final approach taken (completely empirical? or guided by CFD? PAT technology?).

This might seem like a simple project, but as with many things in Chemical Engineering, the devil is very much in the detail. It is not expected to be a walk in the park, but if you make good progress you will find that LEO is very interested in the work, and you will have an excellent thesis and experience for your CV.

Karpiński, P., & Bałdyga, J. (2019). Precipitation Processes. In A. Myerson, D. Erdemir, & A. Lee (Eds.),

Handbook of Industrial Crystallization (pp. 216-265). Cambridge: Cambridge University Press.

doi:10.1017/9781139026949.008

  • Baḱldyga, J., Podgórska, W., & Pohorecki, R. (1995). Mixing-precipitation model with application to double feed semibatch precipitation. Chemical Engineering Science, 50(8), 1281–1300. https://doi.org/10.1016/0009-2509(95)98841-2
  • Bałdyga, J. (2016). Mixing and fluid dynamics effects in particle precipitation processes. KONA Powder and Particle Journal, 2016(33), 127–149. https://doi.org/10.14356/kona.2016021
  • Zauner, R., & Jones, A. G. (2000). Scale-up of continuous and semibatch precipitation processes. Industrial and Engineering Chemistry Research, 39(7), 2392–2403. https://doi.org/10.1021/ie990431u

I samarbejde med
Leo Pharma A/S

Forudsætninger
Experience in CFD

Emneord

  • Bioteknologi og biokemi
  • Fysik
  • Informationsteknologi
  • Kemi
  • Matematik
  • Transport og logistik
  • Teknisk kemi
  • Sundhed og sygdomme
Tags
  • CFD
  • pilotscale
  • Precipitation
  • scaleup
Kontakt
Virksomhed/organisation
DTU Kemiteknik

Navn
Ulrich Krühne

Stilling
Lektor

Mail
ulkr@kt.dtu.dk

Vejleder-info
Kandidatuddannelsen i Kemisk og Biokemisk Teknologi
Vejleder
Ulrich Krühne

ECTS-point
30 - 35

Type
Kandidatspeciale

Skal have taget
28831 Desired

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Danmarks Tekniske Universitet (DTU)
Danmarks Tekniske Universitet (DTU)
DTU er et teknisk eliteuniversitet med international rækkevidde og standard. Vores mission er at udvikle og nyttiggøre naturvidenskab og teknisk videnskab til gavn for samfundet. 11.200 studerende uddanner sig her til fremtiden, og 6.000 medarbejdere har hver dag fokus på uddannelse, forskning, myndighedsrådgivning og innovation, som bidrager til øget vækst og velfærd.

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