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M. Sc. Birte Grönniger

M. Sc. Birte Grönniger Foto von M. Sc. Birte Grönniger



Fakultät Bio- und Chemieingenieurwesen
Emil-Figge-Str. 70
44227 Dortmund

Raum G2-114b

Influence of the viscosity on the crystallization behavior of ASD‘s


The poor aqueous solubility of active pharmaceutical ingredients (APIs) is a major challenge in pharmaceutical industry as it leads to low bioavailability. Stabilizing APIs in polymers and thus producing an Amorphous Solid Dispersion (ASD) has proven to be a successful way to overcome this issue [1]. ASDs are often thermodynamically unstable under storage conditions, such that re-crystallization of the API will occur. Thereby, a strong dependency of the crystallization kinetics on the storage conditions is observed, whereby molecular mobility turns out to be a key factor [2].


The aim of this project is to predict the crystallization kinetics of ASDs under different storage conditions by understanding and connecting thermodynamic factors and molecular mobility. To this end the thermodynamic properties of the system in equilibrium are described using the PC-SAFT equation of state, whereas the experimental determination of the viscosity is used as an indicator for molecular mobility [3]. The viscosity as a function of temperature, Polymer/API ratio and humidity is described using the well-known Williams-Landel-Ferry (WLF) equation. Beyond, the change in viscosity in the region of the glass transition is investigated.

Understanding the influence of storage conditions on molecular mobility and thermodynamic driving forces is needed in order to make reliable predictions of crystallization onset as well as crystallization velocity of the drug in a polymer matrix.




[1] T. Vasconcelos, B. Sarmento, P. Costa:
"Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs"
Drug discovery today 12 (23-24), S. 1068–1075, 2007.
[2] J. A. Baird, L. S. Taylor:
"Evaluation of amorphous solid dispersion properties using thermal analysis techniques"
Advanced drug delivery reviews 64 (5), S. 396–421, 2012.
[3] J. Gross, G. Sadowski:
"Perturbed-Chain SAFT: An Equation of State Based on a Perturbation Theory for Chain Molecules"
Ind. Eng. Chem. Res. 40 (4), S. 1244–1260, 2001.