Analysis of the molecular speciation of organic compounds in solution is essential for the
understanding of ionic complexation. The Raman spectroscopic technique was chosen for
this purpose because it allows the identification of compounds in different states and it
can give information about the molecular geometry from the analysis of the vibrational
spectra. In this research the ionisation steps of relevant pharmaceutical material have been
studied by means of potentiometry coupled with Raman spectroscopy; the protonation
and deprotonation behaviour of the molecules were studied in different pH regions. The
abundance of the different species in the Raman spectra of aqueous salicylic acid,
paracetamol, citric acid and salicylaldoxime have been identified, characterised and
confirmed by numerical treatment of the observed spectral data using a multiwavelength
curve-fitting program. The non-destructive nature of the Raman spectroscopic technique
and the success of the application of the multiwavelength curve-fitting program
demonstrated in this work have offered a new dimension for the rapid identification and
characterisation of pharmaceuticals in solution and have indicated the direction of further
research.
The work also covers the formation of novel cocrystal systems with pharmaceutically
relevant materials. The existence of new cocrystals of salicylic acid-nicotinic acid, DLphenylalanine
, 6-hydroxynicotinic acid, and 3,4-dihydroxybenzoic acid with oxalic acid
have been identified from stoichiometric mixtures using combined techniques of Raman
spectroscopy (dispersive and transmission TRS), X-ray powder diffraction and thermal
analysis. Raman spectroscopy has been used to demonstrate a number of important
aspects regarding the nature of the molecular interactions in the cocrystal. Cocrystals of
II
salicylic acid ¿ benzamide, citric acid-paracetamol and citric acid -benzamide have been
identified with similar analytical approaches and structurally characterised in detail with
single crystal X-ray diffraction.
From these studies the high selectivity and direct micro sampling of Raman spectroscopy
make it possible to identify spectral contributions from each chemical constituent by a
peak wavenumber comparison of single-component spectra (API and guest individually)
and the two- component sample material (API/guest), thus allowing a direct assessment of
cocrystal formation to be made. Correlation of information from Raman spectra have
been made to the X-ray diffraction and thermal analysis results.
Transmission Raman Spectroscopy has been applied to the study cocrystals for the first
time. Identification of new phases of analysis of the low wavenumber Raman bands is
demonstrated to be a key advantage of the TRS technique. / Libyan government and Misurata University
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4467 |
| Date | January 2010 |
| Creators | Elbagerma, Mohamed A. |
| Contributors | Edwards, Howell G.M., Scowen, Ian J. |
| Publisher | University of Bradford, Division of Chemical and Forensic Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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