Thesis
Three-dimensional spectroscopic chemical imaging of pharmaceutical tablets
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2022
- Thesis identifier
- T16362
- Person Identifier (Local)
- 201968815
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- There are recognised knowledge gaps in understanding pharmaceutical tablet manufacturing processes, particularly those relating to the relationship between components in the formulation, processing conditions and the resultant final product characteristics. Being able to quantitatively visualise the microstructure of a tablet matrix is essential for better product and process understanding. Vibrational spectroscopic chemical imaging is an established tool in the pharmaceutical industry to characterise the size and distribution of components within tablets. Current methods, however, do not go beyond examining a sample’s single exposed surface area. There are limitations associated with estimating domain size and shape statistics from a two-dimensional (2D) chemical image as the values obtained will depend on where the domain is sectioned, often over- or underestimating its true value. Three-dimensional (3D) imaging has been reported in the literature by using confocal Raman measurements to obtain a depth profile of a sample. However, this depth is typically less than 50 microns, which is smaller than the particle size of many commonly used excipients and active ingredients. This approach is therefore unsuitable for visualising the spatial arrangement of components within pharmaceutical products. For enhanced drug product and tablet manufacturing understanding, new 3D imaging techniques that can provide full visualisation of a tablet’s microstructure must be developed. This thesis presents an alternative method of obtaining 3D chemical images of pharmaceutical tablets by combining Raman mapping and serial sectioning. 3D quantitative image processing methods were developed to provide a means of objectively assessing differences in the spatial distribution of components. A novel domain adjacency method was devised to calculate the contact surface area between each component to provide superior knowledge on the relative position of a material within the tablet matrix and quantify the association between components. To demonstrate the advanced understanding provided by the proposed 3D chemical imaging approach, the method was used to explore differences in the microstructure of tablets with known good and atypical stability behaviour. The physical structure of the tablets could be used to explain the difference in the stability and provided some insights into the possible types of manufacturing techniques used during production. By providing a means to quantify the 3D microstructure of a tablet matrix, these new capabilities provide a method to link product performance with 3D physical characteristics and thereby enhance manufacturing process understanding. This fundamental knowledge could be used to optimise formulation development through designing manufacturing processes that deliver effective medicines with desired performance characteristics, to ultimately reduce development timelines.
- Advisor / supervisor
- Graham, Duncan (Professor of Chemistry)
- Resource Type
- DOI
- Embargo Note
关系
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File | 2022-10-18 | 限制运用 |