- Title
- Development of a continuous flow process towards the synthesis of fluvastatin: a lipid lowering drug
- Creator
- Singata, Mzuvukile
- Subject
- Drug development – South Africa
- Subject
- Drugs --Law and legislation
- Subject
- Pharmaceutical technology -- South Africa
- Date Issued
- 2022-12
- Date
- 2022-12
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/59587
- Identifier
- vital:62175
- Description
- Access to pharmaceuticals in low to middle income countries affects not only the health of a nation, but also the economy. Global pandemics such as the SARS COVID-19 pandemic have demonstrated this disparity. A potential solution to this crisis is an efficient and reliable means of local production of active pharmaceutical ingredients. Current manufacturing plants heavily rely on batch processes as their primary form of production. Batch production has been shown to have numerous disadvantages that impede the reliable production of drugs. Flow chemistry presents a possible solution to this impediment. Numerous advantages of flow chemistry make this technology a better and safer option for production; these include improved safety, faster reaction times and improved reaction control. In this research we present the use of flow chemistry towards the synthesis of fluvastatin, a lipid lowering drug for individuals that suffer from hypercholesterolemia, which is characterised by elevated levels of low-density lipoprotein that is sometimes referred to as bad cholesterol. Chapter 1 provides a detailed description of the background to the problem of hypercholesterolemia; in this chapter the role of cholesterol in the body and how it can end up becoming a problem is outlined. An in-depth analysis of flow chemistry is provided and finally the problem statement, aims and objectives are presented. Chapter 2 give a detailed description of the instrumentation and chemicals used in the research. A description of experimental methodology towards the synthesis of all intermediates in batch and flow systems is provided. Chapter 3 provides all the data collected from the research and describes a multivariate optimization of the intermediates towards the synthesis of fluvastatin. The first intermediate was successfully synthesized in batch (60%) and flow systems at an improved conversion of 98% in a residence time of 15 minutes. The second intermediate was also obtained in batch (32%) and using continuous flow systems at a conversion of 75% and a residence time of 25 minutes. The third intermediate was successfully cyclized in batch using ZnCl2 (50%) and via continuous flow using Amberlite IR120 in a packed column reactor at a residence time of 15 minutes at 95°C, to obtain a conversion of 98%. The final intermediate was successfully synthesized in batch (62%) and in flow; it was obtained at 98% at a residence time of 15 minutes using continuous flow. Chapter 4 provides a conclusion of the study; it also provides a description of the future work and recommendations for this research.
- Description
- Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2022
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (141 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Singata, M Dec 2022.pdf | 3 MB | Adobe Acrobat PDF | View Details Download |