- Title
- Degradation of Paracetamol and other constituents in Perfalgan®: subtitle if needed. If no subtitle follow instructions in manual
- Creator
- Curran,Catherine
- Description
- Abstract text. 5.1 Background Paracetamol (acetaminophen) is useful for the treatment of mild to moderate pain as well as being opiate–sparing. In recent years the problem of poor solubility of paracetamol in water has been overcome and an intravenous formulation of paracetamol developed. In South Africa this is marketed by Bristol-Myers Squibb as Perfalgan®. Each 500 mg or 1g ampoule of Perfalgan® is recommended for single use only and is to be discarded once opened (Medicines.org, n.d.). This is most likely due to concerns about degradation of paracetamol or other ingredients in the solution once exposed to air and sterility issues. However in South Africa where this drug is expensive, some centers use one ampoule for multiple cases over the course of 12-24 hours. No obvious clinical adverse effects have been reported. 5.2 Objective of study The aim of this study was to examine the practice of using a single vial of Perfalgan® in divided doses over the course of a day for different patients by way of assessing the stability of Perfalgan® on exposure to air. The study has three components, namely: 1. In vitro assessment of paracetamol levels on exposure to air and stressors over time. 2. In vitro assessment of levels of the excipients, namely mannitol and cysteine on exposure to air and stressors over time. 3. Assessment of the lipid permeability of paracetamol in Perfalgan® on exposure to air and stressors over time. C Curran 2014 Degradation of paracetamol and other constituents in Perfalgan® 8 5.3 Methodology High performance liquid chromatography (HPCL-UV) was used to determine the concentration of paracetamol and the presence of degradation products in samples taken at set time periods following exposure of Perfalgan® to air and stressors. Initial work was done using pure paracetamol to determine optimal measurement conditions prior to analysing Perfalgan®. The concentrations of the additives and their degradation products were measured using nuclear magnetic resonance (1 H NMR). Appreciable changes in these could indicate a safety hazard or decreased bioavailability. Finally ultraviolet spectroscopy was performed to assess samples at a wider spectrum of wavelengths, instead of the single wavelength used in HPLC. This was used to assess for degradation products which absorb at different wavelengths and therefore may be missed if HPLC was used alone. Ultraviolet spectroscopy was also used to test bioavailability of the drug via the octanol:water partition coefficient under stressed and unstressed conditions. 5.4 Results The paracetamol in Perfalgan® did not degrade on exposure to air over 24 hours. Neither did it degrade on exposure to acid, alkali, oxidative or heat stress. The HPLC retention time was constantly between 3.17-3.29 minutes. 1 H NMR revealed no change in the formulation of Perfalgan® except for the conversion of the oxygen scavenger cysteine to cystine. The octanol:water partition coefficient likewise stayed constant and was in agreement with the value of 0.46-0.49 quoted in the literature (International Programme on Chemical Safety, 2008; McNeil Consumer Healthcare, 2010). 5.5 Conclusion The paracetamol in Perfalgan® did not degrade on exposure to air and other stressors over 24 hours. The formulation as Perfalgan® was likewise found to be stable. The drug retained its lipid permeability over this period.
- Description
- Thesis (MMED) -- Faculty of Health Sciences, 2014
- Date
- 2014
- Type
- Masters theses, text
- Identifier
- http://hdl.handle.net/11260/3165
- Identifier
- vital:43181
- Format
- computer, online resource, application/pdf, 1 online resource (74 pages), pdf
- Publisher
- Walter Sisulu University, Faculty of Health Sciences
- Language
- English
- Rights
- Walter Sisulu University, All Rights Reserved, Open Access
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| Thumbnail | File | Description | Size | Format | |||
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| View Details | SOURCE1 | Degradation of Paracetamol and other Constituents in Perfalgan.pdf | 2 MB | Adobe Acrobat PDF | View Details |