Thesis--Wisconsin. / Vita. Includes bibliographical references.

The characteristics and applications of a novel design of a thin film photocontactor based on the principle of irradiating a 'water bell' with ultraviolet (UV) light a,e considered in this work. Measurements of UV doses received by the liquid films in single passes were made using both actinometric and bioassay-based methods. The chemical actinometer employed was potassium ferrioxalate (K,Fe(C,o.l,)) and the microorganisms used in the bioassay were Pseudomonas stutzeri (mRG) and a repair-deficient strain of Escherichia coli (NCIMB 11190). Good agreement was obtained between the doses measured using actinometry and the E. coli-based bioassay. At higher doses, good agreement was also obtained for the dose estimates made using actinometry and the Ps. stutzeri bioassay. In addition, a hydrodynamic water bell model, previously developed in the literature, was combined with a UV intensity model to predict UV doses with generally good results. Microbially contaminated metal working fluids were identified as a suitable medium for disinfection using the thin film contactor because they are not treatable using conventional UV contactors, and because the systems employed in industry vary widely in scale. Batches of contaminated emulsion ranging in volume from 200 to 1000 L were successfully disinfected. Representative members of the microbial population were isolated, and their changing status throughout treatment recorded. Against expectations, the population showed no capacity for the post-irradiation repair of UV-induced damage. A simplified disinfection model was established in order to model the treatment of batches of contaminated metal working fluids. Preliminary predictions made using a combination of experimental data for the population as a whole and that for individual species coupled with that generated using the hydrodynamic bell model, gave encouraging results.

This study aims at tackling some of the problems often encountered in photostability testing and liquid formulation development. Three anti-cancer drugs will be employed as models; Dacarbazine (DBZ) has well established photostability issues, Axitinib (AXI) and Sunitinib (SUT) are two new drugs only commercially available in solid dosage forms. In ethanol, the photokinetics of these drugs were well described by the newly proposed Φ-order kinetic mathematical model. This has confirmed the photoreversible character of AXI and SUT’s and unimolecular photoreaction of DBZ’s photodegradations. Also, the Φ-order kinetics is proven to describe them better than the usually used classic thermal reaction orders. In aqueous solution, the drugs were found to undergo thermal and photochemical complex degradations, involving at least 3 photoproducts. A new photokinetic approach has been proposed in this work to solving and unravelling the attributes of such complex mechanisms. For the first time, the quantum yields (QY) of the three drugs were determined and found to increase with irradiation wavelength. SUT’s QY were comparable in ethanol and water (QY460 = 0.02), DBZ was found to be more photoefficient in water (QY330 = 0.04 and 0.1, respectively) and AXI in water (QY330 = 0.06 and 0.03). Φ-order kinetics’ potential for the development of reliable actinometers of the three drugs, without prior knowledge of unknown reaction parameters, has also been established. A general equation to describe the isotherm of a (Gn:Hm) guest-host multicomponent complex was proposed in this work to palliate the lack of a strategy for characterising nanosponge-drug complexes. It provides information on both stiochiometry and association constant of the complex. The results indicate that hydrophobic AXI forms a 1:0.8 complex, indicating the possibility of multiple association sites and/or different types of binding. The newly developed AXI/nanosponge liquid formulation has significantly increased solubility (5000-fold) and thermal stability. Furthermore, the photostability of DBZ and SUT were considerably improved by using a strategy based on light-absorption competitors. Their initial velocities reduced from 10 and 3 s-1 (respectively) to 1 and 0.13 s-1. The successful application of these methods to the model anti-cancer drugs has set out new approaches that might be found useful for future treatments of photodegradation data, development of drug-actinometers and liquid formulations of drugs.