The Development and Application of Oil-in-Water Microemulsion Liquid and Electrokinetic Chromatography for Pharmaceutical Analysis

McEvoy, Eamon (2008) The Development and Application of Oil-in-Water Microemulsion Liquid and Electrokinetic Chromatography for Pharmaceutical Analysis. PhD thesis, Waterford Institute of Technology.

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Since the term ‘microemulsion’ was first coined almost fifty years ago to describe clear, isotropic, thermodynamically stable systems composed of oil, water, surfactant and cosurfactant, numerous and varied reports of the applications of microemulsions have appeared in the literature. Reports of the use of microemulsions in separation science began to appear in the literature in the early 1990’s when they were first used as mobile phases for HPLC and as carrier electrolytes for CE separations, particularly for pharmaceutical applications. Although both MELC and MEEKC have been used for the separation of a wide range of components, MEEKC has received the most attention in recent years as it can be used for the separation of both charged and neutral solutes has been shown to be particularly useful for rapid chiral separations. The main objective of this study was the development of rapid O/W MELC and MEEKC methods for the analysis of pharmaceutical compounds in highly hydrophobic formulations which require lengthy sample preparation and extraction procedures prior to analysis using currently preferred techniques such as titration and RP-HPLC. Both cationic and anionic microemulsions were successfully utilised for the O/W MELC analysis of paracetamol in a suppository and ibuprofen in a cream formulation. The results of validation studies were very favourable and the method for the analysis of the suppository was extremely rapid and easy compared to the reference method. Analysis times for the cream were also rapid and were comparable to sample preparation and analysis times using the reference method. Similarly O/W MEEKC methods for the analysis of paracetamol in a suppository using cationic and anionic microemulsions were very rapid and validation results were comparable to those achieved with O/W MELC. Investigations into the stability of microemulsions under gradient MELC conditions showed that the length of the surfactant alkyl chain was the major factor affecting the systems stability and hence chromatographic reproducibility. The reproducible separation of paracetamol and five of its related impurities in a suppository sample was achieved using a novel isocratic MELC method with a stable diluted CTAB microemulsion as eluent. The most stable microemulsions under diluted conditions were found to be formed with surfactants of longer alkyl chain lengths. Rapid O/W MEEKC methods for paracetamol impurity profiling using both anionic and cationic microemulsions were also developed, however the methods sensitivities were too low for impurity detection at 0.1% levels. The higher solubilising power of longer alkyl chain surfactants was highlighted One of the most active areas of MEEKC research to date has been chiral separations. Various chiral selectors such as; cyclodextrins, chiral oils, chiral alcohols etc have been incorporated into the microemulsions and successfully used to achieve enantioseparation using MEEKC. To date there have been no reports of chiral separations using MELC techniques. The effects of using chiral components in the microemulsion mobile phase for the separation of a number of chiral pharmaceutical compounds were assessed. Microemulsions modified with β-cyclodextrin, a chiral bile salt and a chiral oil phase were used to assess the separations achieved for ibuprofen, ketoprofen, baclofen, atenolol and procyclidine HCl. No chiral separations were achieved, however the effects of surfactant type, microemulsion pH, modifier type & concentration and column temperature were found to effect the achiral separations of the test compounds.

Item Type: Thesis (PhD)
Uncontrolled Keywords: Microemulsion, Electrokinetic chromatography
Departments or Groups: Pharmaceutical and Molecular Biotechnology Research Centre
Divisions: School of Science > Department of Chemical and Life Sciences
Depositing User: e- Thesis
Date Deposited: 23 Oct 2008 10:41
Last Modified: 22 Aug 2016 10:25

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