https://www.um.edu.mt/library/oar/handle/123456789/90864 Mon, 15 Jun 2026 07:46:43 GMT 2026-06-15T07:46:43Z https://www.um.edu.mt/library/oar/handle/123456789/96430 Title: Probing the solid-state behaviour of pharmaceuticals under different environmental conditions Abstract: The aim of this study is to understand the solid-state properties of imatinib, the free base of imatinib mesylate (Gleevec ®), an active pharmaceutical ingredient (API) that is used to treat chronic myelogenous leukaemia under different environmental conditions using crystal engineering techniques. The behaviour of imatinib after grinding with acidic co-crystal formers was studied, where the API’s solubility was measured in water using UV-Vis techniques. The solubility of imatinib in water improved significantly when ground with acidic co-crystal formers and when ground with pyridoxine. Imatinib free base was recrystallised from several solvents and solvent mixtures, from which one major polymorphic form was detected. The unit cell parameters as well as the atomic co-ordinates were determined. The crystal structure of imatinib free base has been determined but further parameters are still required. Rietveld refinement would be required so that any differences between the experimental powder pattern and modelled crystal data are minimised. This process would validate the structure solution which can eventually be published. Description: M.Sc.(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/96430 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/96429 Title: Characterisation and solid-state behaviour of Sunitinib Malate in its various crystalline forms Abstract: The aim of this project was to study and characterise the solid- state behaviour of sunitinib malate in its various crystalline forms. Sunitinib malate is an active pharmaceutical ingredient (API) used for the treatment of renal cell carcinoma, neuroendocrine tumours and imatinib- resistant gastrointestinal stromal tumours. This API is characterised by low bioavailability as it has pH- dependent solubility, where as pH increases, the solubility decreases. A solubility screen was carried out to compile information regarding the behaviour of the API in different solvents and solvent mixtures. This was followed by a polymorph screen. All polymorph samples were analysed through optical and hot stage microscopy, IR- spectroscopy and powder X-ray diffraction (PXRD). From the proposed solid- state characterisation techniques, three samples exhibited changes. Definite confirmation of formation of three different polymorphs or solvates was given based on PXRD data. Cocrystal screening was carried out to study the effect of different stoichiometric ratios on cocrystal formation. Eight GRAS molecules were chosen throughout the author’s B.Sc. and 1: 1- API: coformer samples were synthesised. For this project, identical conformers were chosen and 1: 2- API: coformer samples were prepared. All prepared samples where characterised using hot stage microscopy, IR- spectroscopy and PXRD. It was deduced that different stoichiometric ratios allow the formation of different products. This was confirmed through analysis of PXRD data where there was the formation of a total of seven new crystalline forms. The solid- state behaviour was also tested through solubility screen of the various crystalline forms of the API, in various pH, mainly pH 1.06, 4.01 and 7.03. Such screen confirmed that methods of solid- state chemistry and crystal engineering, lead to changes in physical properties without altering the structure of the API. An overall improvement in all polymorphs and cocrystal samples was noted. This suggests that various crystalline forms of the API might be more effective for treatment purposes, as the higher the solubility, the more the bioavailability of the drug. Description: M.Sc.(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/96429 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/96427 Title: Fluorescent Naphthalimide logic gates in Micelles Abstract: A series of novel 4-amino-1,8-naphthalimide H± sensors were designed and synthesised with an ‘anchor1-spacer1-fluorophore-spacer2-receptor1-anchor2’ format. A scaffold based on the naphthalimide fluorophore, piperazine receptor and butyl chain anchor remained constant throughout the compounds. The variable anchor1 at the imide position was either a methyl, phenyl or 3,4-dimethoxyphenyl substituent. A fourth sensor bears a crown ether with a ‘receptor1-spacer1-fluorophore-spacer2-receptor2-anchor1’ format. A green fluorescence emission is modulated by photoinduced electron transfer (PET) and internal charge transfer (ICT) mechanisms, and by solvent polarity. Experiments were performed in aqueous solutions of CTAC (cetyltrimethylammonium chloride), Triton X-100TM and SDS (sodium dodecyl sulphate). UV-Vis absorbance and steady-state fluorescence spectroscopy were used to study the response of these novel compounds upon altering the nanoenvironment of the micelles. Acid titrations were conducted in surfactant solutions to obtain ΔpKa , lambda maximas and fluorescence quantum yields. These results clearly highlight the repulsive and attractive forces of each surfactant brought about by the charged headgroups and hydrophobic effects. Another set of acid titrations were carried out using model pH probes based on a ‘receptor1-spacer1- fluorophore-spacer2-receptor2’ format without an anchor on the piperazine receptor. These models exhibits a lack of fluorescence switching indicating the butyl chain is essential as an anchor for sensing in micelles. Na± titrations with the crown ether variant uncovered the redundancy of the metal ion as it is dominated by the H± input. Hence all novel sensors function as single-input H±-driven YES gates when probing the micellar interface. Description: M.Sc.(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/96427 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/94800 Title: Investigation of levels of some heavy metals (Cr, Cu, Zn, As, Se, Cd, and Pb) present in cattle fodder, water, milk, hair and manure in Malta Abstract: The objective of this study was to assess the levels of seven heavy metals, four essential elements, Cr, Cu, Zn and Se, and three toxic elements, As, Cd and Pb, through the life cycle of cattle from the dairy cattle farm in Malta, to determine the pollution levels, by using two different equipment. The first technique used was Atomic Absorption Spectrometry (AAS) in which 110 milk, 110 hair, 15 fodder, and 11 manure samples were collected in 11 weeks, started at the last week of September and finished in mid-December, and their heavy metal concentrations were determined for Cu only. The conventional method was used to prepare all these samples. Cu concentration in milk samples showed high levels in each animal separately during this study’s period, which was found to be higher than the maximum level of 0.010mg/l, in accordance with FAO & WHO. The concentration was significantly high in Autumn, whereas it reached its lowest in Winter. On the other hand, the hair samples results had much higher concentrations than those in milk. The Cu concentration was relatively affected by colour. The highest Cu concentration was noted in black haired cows, while the cows with brown hair colour presented similar results but less than the black-haired one. In addition, Cu concentration in fodder showed that there is a significant difference between several types of fodder. Moreover, in manure samples the highest Cu concentration was in week 5, while the lowest was noted in week 7. Manure, fodder and hair had no significant seasonal effect. The second technique, Inductively Coupled Plasma - Optical Emission Spectrometry (ICPOES), was used on all seven heavy metals for a period of one year for all samples, except for hair which had a period of 8 months instead, to observe the seasonal effect. The microwave digestion preparation method was used. Cr resulted to have the highest seasonal effect, for all types of samples, during Winter, Spring and early Summer, with its highest concentrations being 0.880 ]] ppm in fodder, 0.720 ppm in hair, and 0.027 ppm in milk. Cu had the highest seasonal effect during the seasons of Winter and Spring for all samples and was also high in early Summer in hair. Its concentrations were 17.9 ppm in fodder, 10.9 ppm in hair, and 0.213 ppm in milk. Zn was found to be predominant in all samples during the season of Winter, along with milk and hair also having high levels during Summer, with concentrations of 63.1 ppm in fodder, 149 ppm in hair and 6.81 ppm in milk. As had the most seasonal effect during Summer or Winter, with the majority being in Summer. The concentration in fodder was 0.780 ppm, 1.22 ppm in hair, and 0.181 ppm in milk. Se reached seasonal effect during each season except for Winter, with most elements being mostly affected in Spring and Summer. Its highest fodder concentration was 0.740 ppm, hair was 0.130 ppm and milk 0.113 ppm. Cd concluded with seasonal effect being mostly present during Spring, except for Manure, which was highest during Winter, with concentrations of 0.080 ppm in fodder, 0.060 ppm in hair and 0.017 ppm in milk. The overall concentrations of Cd were lower than the permissible limit of 0.005 ppm. Lastly, Pb, resulted in being affected in each season, except for Autumn, with concentrations of 0.380 ppm in fodder, 0.130 ppm in hair and 0.007 ppm in milk. Pb was found to be higher than the permissible limit of 0.020 ppm. With regards to water, all samples were seasonally affected, however, their concentrations remained within the permissible limit. As for manure, it had the highest concentrations out of all the inputs and outputs, which is a positive result since manure does not directly affect the human food chain. The analysis of all the seven heavy metals’ concentrations in milk were determined using two digestion methods and comparing them for the preparation of samples. It was concluded that good recovery was achieved for both methods, in which method 1 presented higher concentrations in all elements, except for As and Se. Zn presented no changes. Furthermore, a comparison between black and white hair was carried out, resulting in no noticeable significance, except for a mild difference in Cr. This study concluded that the presence of some heavy metals’ concentrations are alarming indicators of high level of pollution in Malta. Description: Ph.D.(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/94800 2021-01-01T00:00:00Z