Graduation date: 1956

Graduation date: 1959

Graduation date: 1960

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.

Graduation date: 1960

Graduation date: 1959

Graduation date: 1960

Graduation date: 1961

The storage life at 43°F of ground dover sole fillets (Microstomas pacificus) was determined microbiologically after treatment with ionizing radiation and antimicrobial agents. Sodium benzoate, potassium sorbate and the sodium salts of the methyl and propyl esters of parahydroxybenzoic acid (MPB and PPB) all approximately doubled the refrigerated storage life of irradiated dover sole. The dose levels employed were 0.1, 0.3, and 0.5 Mrad. The concentration of the agents used in each case was 0.1 percent. The normal spoilage of dover sole is caused predominately by the outgrowth of pseudomonads. After irradiation, however, the spoilage is due to the outgrowth of Achromobacter and certain Gram positive organisms. The spoilage pattern was not changed by the antimicrobial agents tested except at the higher dose level (0.5 Mrad), at which the spoilage was caused by yeasts. The additives had no effect on the growth rate of the microorganisms of dover sole. They merely prolonged the length of microbial dormancy that followed radiation exposure. Possible mechanisms involved in the combined effect of antimicrobial agents and irradiation are discussed. / Graduation date: 1965

Graduation date: 1962