The pore geometry of pharmaceutical coatings: statistical modelling, characterization methods and transport prediction
Doctoral thesis, 2020
In Paper I, a Gaussian random field based pore model was developed and fitted to microscopy images of the coating material. Due to the large size of the data, the model was formulated using a Gaussian Markov random field approximation, which allows for efficient inference. A new method for solving linear equations with Kronecker matrices which reduced the complexity of the model fitting algorithm considerably was developed. The pore model was found to fit the microscopy images well. In Paper II, characterization measures that have been shown to provide good regression models for diffusive transport rates were developed further and implemented. Multiplicative regression models were fitted to pore structures from the model from Paper I, and the new methods were shown to give improved results. In Papers III and V characterization measures that capture a type of bottleneck effect which was observed in another set of microscopy images of the coating material (Papers III and IV), but which is not captured by existing methods, were invented. Pore structures with this type of bottleneck were generated using 3-D statistical pore models, and the new type of bottleneck was found to be an important determinant of diffusive transport rates when the regression models were fitted to simple pore structures (Paper V).
Sandra Eriksson Barman
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
A three-dimensional statistical model for imaged microstructures of porous polymer films
Journal of Microscopy,; Vol. 269(2018)p. 247-258
Prediction of diffusive transport through polymer films from characteristics of the pore geometry
AICHE Journal,; Vol. 65(2019)p. 446-457
Barman, S., Fager, C., Röding, M., Lorén, N., von Corswant, C., Olsson, E., Bolin, D., Rootzén, H. New characterization measures of pore shape and connectivity applied to coatings used for controlled drug release
Fager, C., Barman, S., Röding, M., Olsson, A., Lorén, N., von Corswant, C., Bolin, D., Rootzén, H., Olsson, E. 3D high spatial resolution visualisation and quantification of interconnectivity in polymer films
Barman, S., Rootzén, H., Bolin, D. New measures of bottleneck effects in pore geometries evaluated through prediction of diffusive transport
We have developed methods which capture properties of the pore geometry that determine the drug release rate. The methods are based on a virtual experimental setup, where virtual materials were generated from statistical models of the coating and drug transport was computed in each generated material using a computer model. Virtual experiments have the advantage that it is easy to generate a large dataset in the computer, and large datasets are needed to create good models of how the pore geometry influences the drug transport. Real experiments are much more time-consuming and costly. We also developed statistical methods which were used to create realistic 3D statistical models of the coating structure. One of the main results from the virtual experiments was a set of new methods for capturing a type of bottleneck effect that can slow down the rate the drug is released.
Material structures seen through microscopes and statistics
Swedish Foundation for Strategic Research (SSF), 2014-04-01 -- 2019-06-30.
Probability Theory and Statistics
Areas of Advance
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4740
Chalmers University of Technology
Pascal, Matematiska vetenskaper, Chalmers tvärgata 3
Opponent: Prof. Rasmus Waagepetersen, Department of Mathematical sciences, Aalborg University, Denmark