Multiscale X-ray Characterisation of Cellulose-based Solid Dispersions
Licentiate thesis, 2022
This thesis explores the use of X-ray analysis methods to reveal relationships between structures and morphologies of cellulose-based dispersions to the processing conditions and functional properties of the formulation. The focus is to develop methodologies for multiscale structural characterisation that address the challenges of the inherently low contrast between phases of similar densities and the high sensitivity for radiation damage. In this thesis I show how scanning small and wide-angle X-ray scattering (SAXS and WAXS), ptychographic X-ray computed nanotomography (PXCT) and scanning transmission X-ray microscopy (STXM) can be applied and combined to evaluate multiscale morphologies. First, a partly crystalline solid dispersion of carbamazepine dispersed in ethyl cellulose is imaged with scanning SAXS and WAXS as well as PXCT to develop a workflow for multiscale imaging of solid dispersions. This demonstrates how the nanostructure and type of polymorph can be mapped over a macroscopic sample and image the interior structure of the dispersion with a resolution of 80 nm over an extended sample volume. Secondly, phase separated polymer blends of PLA and HPMC, intended as a polymeric carrier for controlled drug release, are imaged with PXCT and STXM. This reveals the drug distribution as well as the morphology of the two polymer phases, which is related to the dissolution profile of the dispersions, showing a release rate dependent on the morphology of the compound. Finally, the molecular arrangement in melt pressed films is investigated with WAXS to explore changes from water exposure of modified cellulose and relate it to the substituted side chains in the cellulose derivative.
PXCT
WAXS
pharmaceutical formulations
multiscale characterisation
STXM
radiation damage
SAXS
X-ray imaging
solid dispersions
cellulose
Author
Martina Olsson
Chalmers, Physics, Materials Physics
Screening of hydrogen bonds in modified cellulose acetates with alkyl chain substitutions
Carbohydrate Polymers,;Vol. 285(2022)
Journal article
Multiscale X-ray imaging of pharmaceutical dosage forms, M. Olsson, R. Govender, A. Diaz, M. Holler, A. Menzel, M. Sadd, S. Abrahamsen Alami, A. Liljeblad, A. Larsson, A. Matic, M. Liebi.
Morphological analysis of phase separated polymer blends in amorphous solid dispersions for controlled drug release, M. Olsson, R. Nilsson, L. Björn, L. Krupnik, P. Naidjonoka, Y. Chen, J. Avaro, A. Diaz, M. Holler, B. Watts, A. Ziolkowska, A. Larsson, M. Liebi, A. Matic.
Subject Categories
Polymer Chemistry
Physical Sciences
Areas of Advance
Nanoscience and Nanotechnology
Publisher
Chalmers
PJ-salen, Fysik Origo
Opponent: Dr. Tomas Rosén, Treesearch/Department of Fiber and Polymer Technology, KTH Royal Institute of Technology, Sweden