AbstractThis thesis proposes a range of experimental factors to be considered in the production of quality dissolution data which can potentially speed up drug choice in the preformulation stages of drug delivery using UV imaging. The reduction of variation between datasets, often problematic with small scale-dissolution, was considered the primary focus of method development. Focus variation microscopy was used as the complementary imaging technique of choice to quantitatively map the surface topography of drug compacts according to their relative roughness.
Sample preparation which is key for intrinsic dissolution rate measurements (IDR) is covered in Chapters 4 and 5, the parameters used in data collection are also covered in chapter 5. Data analysis is covered in Chapters 6 and 7. Chapter 4 investigated the impact of compaction force and the surface against which the compacts were compressed on the surface topography of the compacts and the IDR data collected. It was observed that the force and compaction surface had an impact on the topography of the compacts for some drugs, however little effect on the IDR values. Chapter 5 explored the effects of varying flow rate on IDR and the surface of drug compacts. The results showed that lower flow rates may not be appropriate for soluble drugs such as paracetamol. Also covered in chapter 5 is the impact of drug particle size on the topography of drug compacts and their IDR values. It was observed that particle size had an impact on the surface topography and the IDR values. This was however API dependent.
Chapter 6 studied the impact changes in the IDR measurement zone size and position had on IDR values. It was observed that alterations in the IDR position were more impactful than changes in zone size. Chapter 7 investigated the duration of IDR experiments required to produce quality IDR data. It was found that decreasing the experimental duration is unlikely to significantly affect IDR determinations.
The varying impact of experimental factors highlights that care and consideration needs to be taken/given when conducting IDR determinations using surface dissolution imaging. Also shown is the propensity of APIs to behave differently suggesting many factors are API dependent. This thesis also highlights the value UV imaging has in the ability to visualise dissolution events not commonplace with compendial methods as well as the benefits of surface topography measurements and UV effluent studies as complementary techniques.
|Date of Award||1 Dec 2022|
|Supervisor||Kofi Asare-Addo (Main Supervisor), Karl Walton (Co-Supervisor) & Liam Blunt (Co-Supervisor)|