AYRES, CHARLOTTE,LOUISE (2021) Approaches to Monitoring Dissolution, both on the Surface and in the Bulk. Doctoral thesis, Durham University.
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Dissolution of tablets into their component parts is an important method by which orally-administered formulations are assessed by the pharmaceutical industry. Analysis of dissolution is routinely performed using UV-Vis spectroscopy, which enables compounds containing chromophores to be monitored in the bulk dissolution media. Two additional techniques for monitoring dissolution have been explored with a plan to improve analytical resolution and enhance mechanistic understanding.
The first technique explores surface dissolution imaging (SDI) through UV-Vis technology. Dual-wavelength imaging equipment was used to record changes occurring at the interface between a chromophore-containing solid and a liquid during dissolution. The SDI technique was successfully applied to single crystals, solvates and gels allowing physical and concentration changes to be monitored concurrently. Image analysis software was additionally applied to the UV-Vis absorbance data and the relative stability of a series of solvates was determined.
The second technique monitors dissolution using mass spectrometry (MS) of the bulk liquid. The detection and quantification of a range of APIs and excipients (with and without chromophores) was achieved. Analysis of multiple components by MS without chromatography was found to be subject to significant variability as a result of ion suppression and ion enhancement phenomena. These effects were explored in a step-wise manner to determine the impact of interference and the potential for developing a robust instrumentation configuration to monitor dissolution on-line and in real-time.
The work concludes that each technique has the potential to enhance our understanding of dissolution: SDI through visualising the changes occurring directly in-between the solid and liquid, and MS by enabling the monitoring of soluble excipients in addition to APIs. Although SDI and MS both have limitations preventing their use in conventional dissolution monitoring, each offers a unique opportunity to guide the research and development of new chemical entities and formulations, particularly those exhibiting challenging poorly soluble behaviour.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||"dissolution" "mass spectrometry" "UV-Vis spectroscopy" "surface dissolution imaging"|
|Faculty and Department:||Faculty of Science > Chemistry, Department of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||19 Oct 2021 15:14|