ESR Project 3

Solubility of crystalline APIs and stability of crystal suspension

PhD awarded by:

Technische Universität Dortmund, Germany

Placement:

Janssen (18 months), Technische Universität Dortmund (15 months), University of Limerick (3 months)

Supervisors:

Gabriele Sadowski (TUD), Sarah Hudson (UL), Philippe Fernandes (Janssen)

Eligibility Criteria:

  • MSc in chemical engineering or physical chemistry
  • Applicants must not have resided or carried out their main activity in Germany for more than 12 months in the 3 years immediately before the date of application.

Start Date:

March 2020

Project Details

The objective of this project is for the researcher to gain skills and knowledge on thermodynamic solubility, both from the experimental and theoretical point of view. The researcher will determine solubilities of active pharmaceutical ingredients (API´s) in supercritical CO2 and supercritical CO2 / organic solvent mixtures as a function of pressure, temperature and concentration.

Therefore, a high-pressure apparatus will be used to determine them experimentally. From the theoretical point of view, the PC-SAFT equation of state will be utilized to calculate the relating phase diagrams.   Additionally, the size-dependency of the API solubility in both water and organic solvents will be investigated, especially how the thermodynamic equilibrium solubility changes if the diameter of the API particles reaches the nanoscale. For that manner, the interfacial tension between the solid and the liquid phase will be determined experimentally. Regarding the modelling of this phenomenon, a new theoretical framework will be developed to incorporate this size-dependency into, namely PC-SAFT.   Furthermore, the influence of polymeric excipients on API solubilities will be investigated and best stabilizing excipients for long acting (LA) formulations will be identified.

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