O metronidazol é usado no tratamento de infecções causadas por protozoários e naquelas causadas por microrganismos anaeróbicos, no tratamento das formas intestinais e extra-intestinais de amebíase, em tricomoníase e em infecções bacterianas aeróbicas graves. Após administração oral, a absorção é rápida e completa sendo amplamente distribuído, atinge concentração plasmática máxima em 1-2 horas. A meia-vida de eliminação do metronidazol é de 6-12 horas. O objetivo deste trabalho foi avaliar a equivalência terapêutica por meio da bioequivalêmcia entre duas formulações de comprimidos revestidos contendo metronidazol, produzidos por dois fabricantes distintos, permitindo assim a intercambiabilidade entre as formulações. O ensaio de bioequivalência entre o produto teste (FUNED metronidazol) e o produto referência (Flagyl® - Aventis Pharma Ltda.) foi do tipo randomizado, cruzado e aberto. O medicamento foi administrado em dose única de 250 mg de metronidazol aos 24 voluntários sadios. Amostras de sangue foram coletadas até 48 horas após a administração e analisadas por método, desenvolvido e validado, de cromatografia líquida de alta eficiência acoplada à espectrometria de massas (CLAE- MS/MS). As curvas de decaimento plasmático obtidas para o produto teste (FUNED metronidazol) e para o produto referência (Flagyl® - Aventis Pharma Ltda.) foram semelhantes, assim como os parâmetros farmacocinéticos Cmax (teste: 6,66 µg/mL; referência: 6,77 µg/mL), tmax (teste: 1,26 h; referência: 1,90 h), ASC0-t (teste: 73,42 µgxh/mL; referência: 73,56 µgxh/mL), ASC0-∞ (teste: 75,15 µgxh/mL; referência: 75,23 µgxh/mL) e t½el (teste: 8,00 h; referência: 7,76 h). Os intervalos de confiança 90% para a razão de Cmax (92,2 - 106,4 %), ASC0-t (97,2 - 102,5 %) e ASC0-∞ (97,1 - 102,8 %) encontram-se entre 80 e 125 %, intervalo proposto pela ANVISA e FDA para a bioequivalência. A comparação estatística por meio de análise de variância (ANOVA) dos parâmetros Cmax, ASC0-t e ASC0-∞ indica claramente não haver diferença significativa entre os dois produtos contendo 250 mg de metronidazol. Baseado nos resultados farmacocinéticos e estatísticos, conclui-se que os dois produtos são bioequivalentes e, podem ser considerados intercambiáveis na terapêutica. / Metronidazole is used to treat infections caused by protozoa and those caused by anaerobic microorganisms. It is the drug of choice for the treatment of amebiasis in the intestinal and extra-intestinal forms, trichomoniasis and bacterial aerobic diseases. After oral administration, its absorption is rapid, complete and widely distributed, reaching maximum plasma concentration in 1 to 2 hours. The half-life of elimination of metronidazole is 6 to 12 hours. The objective of this study was to evaluate the therapeutic equivalence through bioavalability between two formulations of tablets containing metronidazole, produced by two different manufacturers, thus allowing the interchangeability between the formulations. The bioequivalence assay between the test product (FUNED Metronidazole) and reference product (Flagyl® - Aventis Pharma Ltda.) was a randomized, crossover and open study. The drug was given at a 250 mg metronidazole single dose to 24 healthy volunteers. Blood samples were collected until 48 hours after administration and analyzed by method, developed and validated in high performance liquid chromatography coupled to mass spectrometry (HPLC - MS / MS). The plasma decay curves obtained for the product test (FUNED metronidazole) and the reference product (Flagyl® - Aventis Pharma Ltda.) were statistically similar in the same way as the pharmacokinetic parameters Cmax (test: 6.66 µg/mL, reference: 6.77 µg/mL), tmax (test: 1.26 h; reference: 1.90 h), AUC0-t (test: 73.42 µgxh/mL, reference: 73.56 µgxh/mL) AUC0-∞ (test: 75.15 µgxh/mL, reference: 75.23). The 90% confidence intervals for the ratio of Cmax (92.2 - 106.4%), AUC0-t (97.2 - 102.5%) and AUC0-∞ (97.1 - 102.8%) are between 80 and 125%, range proposed by ANVISA and FDA for bioequivalence assays. This statistical parameters comparison using analysis of variance (ANOVA) Cmax, AUC0-t and AUC0-∞ clearly indicate no significant difference between the two products containing 250 mg of metronidazole. Based on the pharmacokinetic and statistical results, it is possible to conclude that the two products are bioequivalent and could be considered interchangeable in therapy.

The photocatalytic properties of titanium dioxide have been widely studied over recent decades since the discovery in 1972 of water photolysis by TiO2 electrodes. There are a number of different TiO2 polymorphs. Rutile and anatase are the most studied due to their chemo-physical properties. Under ultraviolet light, TiO2 is able to absorb photons, creating a charge separation on the surface, an electron and a positive “hole”. This electron-hole pair then reacts with water and oxygen, generating radicals, very unstable and reactive species which show great potential for neutralisation of pollutants. In the introduction the state of art of photocatalysis; chemo-physical principles, applications and current analysis are described. A number of protocols to test photoactivity are discussed with particular emphasis on the importance of gas phase reactions. The development of a novel system to study gas phase reactions by mass spectrometry was explored, detailing the conditions and parameters that were optimised. This instrument was used to analyse photocatalytic properties of TiO2 powders and photocatalytic coatings under different UV light conditions. The results showed how TiO2 in the form of anatase and rutile removed nitrogen and carbon dioxide under different UV light sources, with anatase being more effective. A comprehensive study of several commercially available TiO2 powders and coatings was performed to identify the differences between photocatalytic properties, using electron microscopy, Raman and UV-vis diffusive spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. An important question that was answered in this thesis is whether the physical properties of nanoparticles or their electronic properties are critical for their photocatalytic behaviour. Results for anatase powders of different particle size and surface area showed how the positioning of their electronic band gap with the wavelength of the UV light source was fundamental for an effective photocatalyic process. In order to improve the photocatalytic process, “self-doping” TiO2 was investigated. Different reduction temperatures were studied to generate the best ratio of Ti3+-Ti4+ that stabilised the charge distribution process to maximize the electron-hole pairs generated per photon in the gas phase. From a wide range of reduction temperatures, titanium sub-oxime reduced at 400 oC showed the best performance in removing carbon dioxide. In the application of TiO2 for the built environment, the best commercially available TiO2 powder, anatase P25 was applied with two different techniques. Electrophoretic deposition has the potential to scale up the process for prefabricated panels in construction. Solvent, iv deposition time, voltage and substrate were optimised. The resulting photoactivity of the coatings was evaluated showing a higher efficiency than a compressed pellet of anatase P25. The final part of the thesis was dedicated to the formulation and application of a photocatalytic enhanced lime based coatings for the built heritage. The use of calcium hydroxide dispersions is widely used in the conservation and restoration community, reinforcing limestone when it carbonates. Anatase P25, was added to improve the performance in polluted atmospheres, acting as a sacrificial barrier. Results showed that by adding anatase to the formulation, calcium hydroxide reacted preferentially with sulphur dioxide over carbon dioxide. The final product in the formulation with anatase was calcium sulphate, whereas the final product for the calcium hydroxide formulation was calcium sulphite. Finally, a general discussion of the results is presented and the conclusions of this research are drawn. Recommendations for further work are presented in the last chapter.

O metronidazol é usado no tratamento de infecções causadas por protozoários e naquelas causadas por microrganismos anaeróbicos, no tratamento das formas intestinais e extra-intestinais de amebíase, em tricomoníase e em infecções bacterianas aeróbicas graves. Após administração oral, a absorção é rápida e completa sendo amplamente distribuído, atinge concentração plasmática máxima em 1-2 horas. A meia-vida de eliminação do metronidazol é de 6-12 horas. O objetivo deste trabalho foi avaliar a equivalência terapêutica por meio da bioequivalêmcia entre duas formulações de comprimidos revestidos contendo metronidazol, produzidos por dois fabricantes distintos, permitindo assim a intercambiabilidade entre as formulações. O ensaio de bioequivalência entre o produto teste (FUNED metronidazol) e o produto referência (Flagyl® - Aventis Pharma Ltda.) foi do tipo randomizado, cruzado e aberto. O medicamento foi administrado em dose única de 250 mg de metronidazol aos 24 voluntários sadios. Amostras de sangue foram coletadas até 48 horas após a administração e analisadas por método, desenvolvido e validado, de cromatografia líquida de alta eficiência acoplada à espectrometria de massas (CLAE- MS/MS). As curvas de decaimento plasmático obtidas para o produto teste (FUNED metronidazol) e para o produto referência (Flagyl® - Aventis Pharma Ltda.) foram semelhantes, assim como os parâmetros farmacocinéticos Cmax (teste: 6,66 µg/mL; referência: 6,77 µg/mL), tmax (teste: 1,26 h; referência: 1,90 h), ASC0-t (teste: 73,42 µgxh/mL; referência: 73,56 µgxh/mL), ASC0-∞ (teste: 75,15 µgxh/mL; referência: 75,23 µgxh/mL) e t½el (teste: 8,00 h; referência: 7,76 h). Os intervalos de confiança 90% para a razão de Cmax (92,2 - 106,4 %), ASC0-t (97,2 - 102,5 %) e ASC0-∞ (97,1 - 102,8 %) encontram-se entre 80 e 125 %, intervalo proposto pela ANVISA e FDA para a bioequivalência. A comparação estatística por meio de análise de variância (ANOVA) dos parâmetros Cmax, ASC0-t e ASC0-∞ indica claramente não haver diferença significativa entre os dois produtos contendo 250 mg de metronidazol. Baseado nos resultados farmacocinéticos e estatísticos, conclui-se que os dois produtos são bioequivalentes e, podem ser considerados intercambiáveis na terapêutica. / Metronidazole is used to treat infections caused by protozoa and those caused by anaerobic microorganisms. It is the drug of choice for the treatment of amebiasis in the intestinal and extra-intestinal forms, trichomoniasis and bacterial aerobic diseases. After oral administration, its absorption is rapid, complete and widely distributed, reaching maximum plasma concentration in 1 to 2 hours. The half-life of elimination of metronidazole is 6 to 12 hours. The objective of this study was to evaluate the therapeutic equivalence through bioavalability between two formulations of tablets containing metronidazole, produced by two different manufacturers, thus allowing the interchangeability between the formulations. The bioequivalence assay between the test product (FUNED Metronidazole) and reference product (Flagyl® - Aventis Pharma Ltda.) was a randomized, crossover and open study. The drug was given at a 250 mg metronidazole single dose to 24 healthy volunteers. Blood samples were collected until 48 hours after administration and analyzed by method, developed and validated in high performance liquid chromatography coupled to mass spectrometry (HPLC - MS / MS). The plasma decay curves obtained for the product test (FUNED metronidazole) and the reference product (Flagyl® - Aventis Pharma Ltda.) were statistically similar in the same way as the pharmacokinetic parameters Cmax (test: 6.66 µg/mL, reference: 6.77 µg/mL), tmax (test: 1.26 h; reference: 1.90 h), AUC0-t (test: 73.42 µgxh/mL, reference: 73.56 µgxh/mL) AUC0-∞ (test: 75.15 µgxh/mL, reference: 75.23). The 90% confidence intervals for the ratio of Cmax (92.2 - 106.4%), AUC0-t (97.2 - 102.5%) and AUC0-∞ (97.1 - 102.8%) are between 80 and 125%, range proposed by ANVISA and FDA for bioequivalence assays. This statistical parameters comparison using analysis of variance (ANOVA) Cmax, AUC0-t and AUC0-∞ clearly indicate no significant difference between the two products containing 250 mg of metronidazole. Based on the pharmacokinetic and statistical results, it is possible to conclude that the two products are bioequivalent and could be considered interchangeable in therapy.