Saudi Cultural Missions Theses & Dissertations
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Item Restricted Electrochemical dissolution of Fe in concentrated aqueous electrolyte(University College London, 2024) Almalki, Hind; Holt, KatherineAll-iron aqueous redox flow batteries provide a low-cost, safe solution for energy storage by utilising the Fe(II)/Fe(0) couple (Fe0 → Fe2+ + 2e-) at the anode and the Fe(III)/Fe(II) couple (Fe3+ + e- → Fe2+) at the cathode. While the simplicity of this battery design is attractive, several fundamental challenges must be overcome to allow full exploitation. These include slow kinetics for the Fe2+/Fe0 plating and stripping reaction leading to decreased coulombic efficiency and competing H2O reduction at the Fe electrode leading to harmful H2 generation. In this thesis the Fe2+/Fe0 redox response, measured using cyclic voltammetry, varies with electrolyte concentration (from 0.1 M to 2.5 M Li2SO4). At lower concentrations (from 0.1 M to 1.8 M), the iron dissolution rate increases with the electrolyte concentration and the reaction is rapid. At high concentrations (2.0 M and above), the CV results found that the current drops and the iron dissolution reaction stops. To understand these results, the viscosity, conductivity, and infrared spectra of lithium sulfate solutions were measured with different concentrations. The viscosity increases with increasing concentration from 0.1 to 1.8 M. Also, the conductivity increases as the concentration increases from 0.1 to 1.8 M. When concentrations exceed 1.8 M, the viscosity increases more significantly and there is no further increase in conductivity values. Turning to the infrared result, there are changes in the structure of water in the electrolyte with increasing concentration. From 0.1 to 1.8 M, ions are more independent of each other. When concentrations reach higher than 1.8 M, an ionic interaction occurs between sulfate and lithium, which causes sulfate to lose its symmetry, which is reflected in the IR spectra. Changes also occur in the hydrogen bonds of water as a result of the trapping of water molecules by electrolyte ions. These results together suggest that the slower oxidation of iron at higher concentrations could be due to increased solution viscosity or decreased conductivity due to ions interacting with each other through ion-pairing. Raman spectroscopy of the iron electrode after oxidation shows formation of iron sulfate surface films in Li2SO4, which indicates that electrode passivating reactions within the aqueous electrolyte are taking place at 2.0 M and above. This result is consistent with the CV results where the dissolution of iron stopped, and the current became passivated. This passivation is due to the formation of the iron sulfate film. In-situ IR spectroelectrochemistry data shows changes to water and electrolyte structure at potentials at which Fe dissolution takes place. At low concentrations, the sulfate peak is more symmetrical, and sulfate does not lose its symmetry, and therefore each ion dissolves separately and does not interact much with other ions. At high concentrations, the IR results show changes in the asymmetric sulfate stretch due to the loss of sulfate symmetry and the appearance of a new peak in the symmetric stretch region. This indicates the presence of interactions between ions in the solution and the formation of ion pairs. The effect of adding 4.5 M MgCl2 to different concentrations of Li2SO4 was also investigated to improve the dissolution efficiency of the iron electrode. The results of cyclic voltammetry showed that the dissolution of iron became faster and the deposition of a layer of iron sulphate on the electrode was prevented as the Raman spectra showed few vibrational peaks of sulfate. The IR absorption results show the sulfate peak loses its symmetry at low concentrations. This is because the increase in the number of ions in the solution leads to increased interaction of sulfate with surrounding ions, which leads to broadening and splitting of the peak. Finally, the redox response of Fe2+/Fe0 in LiTFSI from 0.1 M to 15 m was studied. The reaction current decreased and the dissolution rate of iron decreased due to the large size of TFSI anions and the high viscosity of the solution. However, no passivation layer was formed on the surface with adsorption of TFSI- anions on the surface according to the Raman and IR results.11 0Item Restricted Studies of class II drugs-amino acid hydrotrope and dissolution of freeze dried co-amorphous formulations(2023-05-01) Alsalhi, Mohammed Suleiman; Chan, Ka Lung AndrewBackground The aqueous solubility and dissolution of active pharmaceutical ingredients (APIs) are defined as the most critical issues plaguing the development pipeline of solid formulations in the pharmaceutical industry. An estimated 40% of market approval drugs and 90% of the new API suffer from poor water solubility. Amino acids have shown promising abilities to form complexes with poorly water-soluble drugs (PWSDs) and improve their physicochemical properties. Amino acids have the advantages of being generally regarded as safe, organic, natural and low molecular weight excipients with varying in size, hydrophobicity and polarity, and the ability to produce various non-ionic or/and ionic interactions or as hydrotropes with drug molecules to improve the solubility and dissolution of PWSDs. However, there is still a lack of understanding of amino acids at the molecular level in their ability to enhance the aqueous solubility of PWSDs. A freeze drying method also has not been investigated yet for its ability to successfully produce a CAM system that has non-ionic interactions between PWSD and amino acid. Aim The main aim of this thesis is to demonstrate the potential to enhance the aqueous solubility and dissolution properties of class II BCS drugs using amino acids either as hydrotrope or as the low molecular weight (LMW) hydrophilic excipients via formulating co-amorphous (CAM) system by freeze drying method using TBA-water solvent system. Methods The molecular basis of hydrotropic interactions was demonstrated by investigating two model class II BCS drugs (carbamazepine and indomethacin) combined with 12 amino acids including phenylalanine, tryptophan, isoleucine, proline, valine, glycine, serine, threonine, arginine, lysine, histidine and aspartic acid in water by UV-Vis and NMR spectroscopies at 25 ◦C, 30 ◦C and 45 ◦C. The amino acids were chosen based on their different side chains (neutral aromatic, aliphatic, polar charged or uncharged) to investigate their hydrotropic performance. II The mechanism of solubility enhancement study has evaluated the contribution of non-ionic interactions in salt-based CAM systems between a model acidic drug, indomethacin, and basic amino acids, arginine, lysine and histidine in a water solvent system using UV-Vis and FTIR spectroscopies. Freeze drying was used to produce the salt drug-amino acid CAM for further characterization of their interactions in the solid phase using thermal analysis (DSC and TGA) and spectroscopy. The non-salt-based CAM system study has explored the potential of freeze drying as an efficient manufacturing process to produce a CAM system that has weak non-ionic interactions between the amino acid and the drug using the tert-butyl alcohol (TBA)-water cosolvent system. The liquid, frozen solutions and freeze-dried materials were systemically characterised for their thermal properties or physical cake appearance, residual solvent, amorphous formation, molecular interactions and drug content using a number of techniques (e.g., DSC, TGA, XRPD, FTIR and UV Vis). The optimal drug: co-former ratio for dissolution profile and long-term storage stability was also evaluated. Results In the hydrotropic study, a linear solubility curve was observed between indomethacin and mono-neutral hydrophobic amino acids (phenylalanine, tryptophan, isoleucine, proline and valine) at a molar ratio of well beyond 1:1 indicating that the interaction is predominantly non ionic between the drug and the hydrotropes. Interestingly, the aqueous solubility of carbamazepine (a neutral compound) was enhanced by neutral, charged basic or acidic amino acids, confirming the presence of hydrophobic interactions that involve H-bonds, H/π and π/π stacking. The results were confirmed by UV-Vis and NMR spectroscopies. The combination of multiple neutral amino acids has shown an additive hydrotropic effect in the indomethacin solubility study with up to 7-fold increase being observed. In the mechanism of solubility enhancement study, at low concentrations of amino acids, indomethacin-arginine or lysine complexes have shown a linear relationship (AL-type phase solubility diagram) between indomethacin solubility and amino acid concentrations, producing III 0.92:1 or 0.97:1 (near stoichiometry) molar ratio of drug-arginine or lysine complexes, respectively as expected due to the strong electrostatic interactions. However, indomethacin histidine complexes have shown a nonlinear relationship with lower improvement in indomethacin solubility due to the weaker electrostatic interactions when compared to arginine and lysine. Interestingly, the results have also shown that at high arginine concentrations, the linearity was lost between indomethacin solubility and amino acid concentration with a negative diversion from linearity, following the type-AN phase solubility. This is indicative of that the electrostatic interaction is being interrupted by non-electrostatic interactions, as seen with histidine. The indomethacin-lysine complex, on the other hand, has shown a complex curved phase solubility diagram (type BS) as lysine self-assembles and polymerizes at higher concentrations with results showing the involvement of weak non-ionic interactions. Non-ionic interactions including H-bonds, H/π and π/π stacking were confirmed to be involved in the salt based CAM systems between acidic drugs and basic amino acids using FTIR spectroscopy. In the non-salt-based CAM system study, freeze-drying appears to be able to successfully produce non-salt CAM with a uniform and elegant cake appearance using the cosolvent system. The molecular interactions involved H-bonds, H/π and π–π between compounds have been confirmed to be involved. Interestingly, the drug release rate of 70% w/w drug loading and below formulations were superior compared to the pure crystalline drug. Further, formulations with below 80% w/w drug loading have shown to be physically stable over 9 months at dry condition/25 °C. The optimal ratio between indomethacin and tryptophan, based on the long term storage physical stability result and dissolution profile is higher than the 1:1 molar ratio (1:0.53 weight ratio), although a 1:1 ratio is often used in producing the CAM system. Conclusion This research demonstrates for the first time the potential of amino acids as hydrotropes to improve aqueous solubility of PWSDs. It also confirms the solubility improvement of the insoluble acidic drug in the presence of basic amino acids was due to not just the ionic interactions but also has some contribution from non-ionic interactions. The gentle freeze drying method has also shown to be a feasible technique for producing non-salt CAM poorly class II drug to amino acid IV with the TBA-water cosolvent system, with an improved dissolution rates and physical stability upon long-term storage. The non-ionic CAM system is important as these interactions do not alter the structural or functional properties of drugs, and also are less dependent on the pH, and thus may help to overcome issues such as disproportionation on storage and dissolution. An understanding, at the molecular level, of the CAM systems is important to achieve their full performance and optimum use in the oral delivery route12 0