Multiscale X-ray Characterisation of Cellulose-based Solid Dispersions
Licentiate thesis, 2022

Cellulose-based solid dispersions are a promising formulation strategy for providing controlled drug release and dissolution enhancement of poorly soluble drugs. These dispersions can from structures on multiple length scales which can have both positive and negative effects on the functional properties of the formulation. For instance, phase separated morphologies can affect the solubility and release profile of a drug dispersion. Such structures can form both during the processing step or evolve during storage and dissolution. For the development of new pharmaceutical dosage forms and drug delivery systems it is important to develop a better understanding of how these structures are formed and how they will affect the properties of the dispersion. A first step towards establishing this is to develop methodologies for structural characterisation over multiple length scales. 

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

PJ-salen, Fysik Origo
Opponent: Dr. Tomas Rosén, Treesearch/Department of Fiber and Polymer Technology, KTH Royal Institute of Technology, Sweden

Author

Martina Olsson

Chalmers, Physics, Materials Physics

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

More information

Latest update

10/27/2023