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Title: Analytical method development for structural studies of pharmaceutical and related materials in solution and solid state : an investigation of the solid forms and mechanisms of formation of cocrystal systems using vibrational spectroscopic and X-ray diffraction techniques
Author: Elbagerma, Mohamed A.
ISNI:       0000 0004 2719 2786
Awarding Body: University of Bradford
Current Institution: University of Bradford
Date of Award: 2010
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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 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.
Supervisor: Edwards, Howell G. M. ; Scowen, Ian J. Sponsor: Libyan government and Misurata University
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: In situ monitoring ; Acidity constants ; Multiwavelength spectroscopy ; pH ; Cocrystal ; Raman spectroscopy ; X-Ray diffraction ; DSC ; Organic compounds ; Ionic complexation