No description available.

In this work, the radiolysis mechanisms in solids as well as in liquid and frozen aqueous solutions have been studied. Liquid chromatography tandem mass spectrometry has evolved so that mass spectral information can now be used to determine the most probable structures of radiolysis products, even those present in traces amounts. Theoretical routes explaining the formation of radiolysis products can be deduced from their structures. The development of strategies to limit the degradation of the active pharmaceutical ingredient during irradiation of the drug requires a better knowledge of the radiolysis mechanisms responsible for the drug degradation. Metoclopramide, an antiemetic drug, has been selected as a model, due to the variety of its chemical bonds. In the solid state, radiation-induced degradation of the drug was very low (<0.1%) and only four radiolysis products were detected in traces. The “major” radiolysis product was formed after the loss of the chlorine by dissociative electron capture. For metoclopramide liquid aqueous solutions, the loss of the drug was important (~30% loss at 25 kGy) and several radiolysis products were detected. The majority of the degradation products were generated following the attacks of hydroxyl radicals and aqueous electrons. The loss of metoclopramide could be lowered up to acceptable levels (<10% loss) provided that radioprotective additives were added and the irradiation dose was limited to 15 kGy, which could be sufficient to reach the required SAL. The selected excipients were mannitol (which reacts mainly with the hydroxyl radical), nicotinamide and pyridoxine that react with both the aqueous electron and the hydroxyl radical. The irradiation of frozen aqueous solutions allowed to minimize the loss of active substance even for a 25 kGy dose. This approach seems to be the most promising method for terminal sterilization of aqueous solutions by ionizing radiations. The major radiolysis product was formed after the attack of the electron. Some of the radiolysis products detected were attributed to the attack of the hydroxyl radical, demonstrating the feasibility of a reaction between the hydroxyl radical from ice radiolysis and the solute. A comparison was performed with irradiated frozen solutions of metoprolol, which has been studied in liquid aqueous solutions (C. Slegers’ thesis). Degradation of metoprolol when irradiated in frozen solutions was negligible.

No description available.

Biomaterial-associated infections remain a significant complication of medical implants. Of the different strains of bacteria associated with nosocomial infections, 70% are resistant to at least one of the drugs used for treatment (Bren 2002). In 2000 the Center for Disease Control ranked microbial agents as the 4th leading actual cause of death in the United States of America (Mokdad et al. 2004).In an effort to improve the prevention and treatment of infections, this research has three objectives: the development of an alternative sterilization method for medical devices; assessing a new antimicrobial material for the prevention of infections in situ; and assessing mechanisms of acquired microbial resistance. The biocide being investigated in this body of work is chlorine dioxide gas.While multiple sterilization methods are available, there are limitations to all of these technologies. For example, chemical sterilization can leave residues on the surface of the material. These residuals can be toxic, causing sensitization reactions when the materials are implanted in the body (Dolovich et al. 1984; Marshall et al. 1985; Chapman et al. 1986; Dolovich et al. 1987). Research has shown that materials sterilized with increasing concentrations of the chemical sterilizing agent have increasing quantities of residuals (Lyarskii et al. 1984). The studies presented here will ascertain the environmental parameters required for sterilization of biomaterials with low concentrations of chlorine dioxide gas and assess polymers sterilized using these conditions for the cytotoxicity of possible chemical residuals.Investigations into preventing biomaterial-based infections in situ have focused on changing the biomaterial properties. Materials with altered physicochemical characteristics to prevent bacterial adhesion have been developed, and antibiotics and silver have been incorporated into the biomaterials to inhibit bacterial colonization. Unfortunately, the rapid depletion of incorporated antimicrobial agents, altered bactericidal activity in vivo, and the development of antibiotic resistance, have all limited the effectiveness of current technologies. In these studies a chlorine dioxide generating material was assessed using in vitro and in vivo assays.While assessing the bactericidal efficacy of a selection of chlorine dioxide generating materials, a spontaneous bacterial mutant with a reduced susceptibility to chlorine dioxide was isolated. The final section of this work will investigate a potential mechanism of resistance to chlorine dioxide.

Graduation date: 1960

Graduation date: 1959

Graduation date: 1960

Graduation date: 1961

Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1996. / Includes bibliographical references (leaves [240]-267).

Thesis (doctoral) - Universität, Erfurt, 2009. / Includes bibliographical references.