Co-crystals are multi-component, single phase materials in which the co-crystal formers exist in an uncharged state. This interaction between components occurs without affecting the intra-molecular covalent bonding of the involved components or altering their chemical integrity. This class of materials has recently gained the interest in the pharmaceutical industry for modifying the physico-chemical properties of some active pharmaceutical ingredients (APIs) such as solubility, hygroscopicity, and mechanical properties. However like all multi-component systems, there are some analytical challenges associated with using traditional quality control (QC) tools that involve sample preparation steps prior to the analysis. This can sometimes have an impact on the physical state of such systems and therefore affect the outcomes of analysis correlated with the actual materials. Flurbiprofen (FBP) and nicotinamide (NCT) in this work were selected to form a model co-crystal system. FBP falls in the carboxylated group of non steroidal anti-inflammatory drugs (NSAIDs), used herein as an API. It belongs to class II of the Biopharmaceutics Classification System (BCS), therefore its low aqueous solubility and dissolution rate affect its bioavailability. NCT is a vitamin B3 derivative and generally regarded as safe (GRAS) substance. It is used as co-crystallising agent due to its solubility enhancing property. FBP-NCT co-crystal system was previously studied by Berry et al., where a FBP-NCT co-crystal was prepared using Kofler method and screened by means of the hot-stage microscopy (HSM). FBP-NCT co-crystal was recently prepared via rapid evaporation from ethanol solution, and screened for its physicochemical and mechanical properties by Shing et al. who found an improvement in such properties compared to the pure API (FBP). There is a wide range of methods for preparing co-crystals, of which methodologies with minimal environment impact were mainly adopted in this work i.e., Ko er fusion and co-grinding methods. Within the Kofler fusion method, it was feasible to identify and screen simultaneously parent components as well as the emerging material at room temperature (RT) by means of confocal Raman microscopy. Detailed information from Raman mapping on the investigated phases were achieved using statistical analysis. The analysis resulted in a refinement regarding the traditional assumption about the binary phase diagram. It also revealed the presence of two forms of FBP-NCT co-crystals which were consequently explored by coupling thermal analysis with Raman spectroscopy and X-ray diffraction. Using co-grinding preparation, FBP-NCT co-crystals were prepared on a large scale; enough for solid dosage formulation. Subsequent crystallisation of the resulting compound using a solution method generated single crystals suitable for x-ray crystal structure determination. Moreover in this work, a solid-state dosage form of FBP-NCT co-crystal was prepared for the first time, then investigated using transmission Raman spectroscopy. The investigation included the presence of drug and excipient, and their composition in tablets. This procedure can be considered as a platform for studying the QC of drug preparation, using a reliable, non-destructive, non-invasive, and very rapid analytical tool. Such type of study complied well with the food and drug administrative (FDA) outlines on employing process analytical technology (PAT) protocol for analysing and controlling pharmaceutical manufacturing processes.

The bactericidal mechanism of hydrogen peroxide is poorly understood, with most evidence being obtained from studies involving greatly reduced concentrations aimed at investigating the effects of stress. Current theory suggests that this mechanism is based on the oxidation of protein, DNA and lipids within the cell by the production of free hydroxyl radicals through the interaction of hydrogen peroxide and intracellular iron. The mechanism of vapour phase hydrogen peroxide treatment remains unstudied, despite evidence that it may be different to the liquid phase. This study aimed to investigate the effects of bactericidal treatments of liquid and vapour phase hydrogen peroxide on the macromolecular components of a model organism, Escherichia coli strain K12. A set of treatment conditions producing a range of reductions in colony forming units was identified, and the effects of these conditions on the protein, DNA and lipid constituents of the cells assayed. No effect on the lipid contents and membrane integrity of treated cells was found. Liquid hydrogen peroxide was found to reduce the thiol content of cytoplasmic protein, but this was not found to be a major mechanism of bactericidal action. Extensive fragmentation of DNA was found to result by treatment with both phases, the degree of which was correlated with a reduction in colony forming unit counts. No effect on bactericidal action was found on addition of a hydroxyl radical scavenger or an inhibitor of protein synthesis, showing that DNA damage was due to the primary action of hydrogen peroxide, and that this damage was not caused by the production of free radicals within the cell. A modifed mechanism of hydrogen peroxide bactericidal action is proposed, whereby lethality is due solely to DNA damage caused by the production of ferryl radicals by the interaction of hydrogen peroxide and iron associated with the DNA backbone.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban Institute of Technology, 2007. / Group analysis of homoeopathic remedies is a relatively new methodology, linking naturally related substances via their common symptomatology. At its very basic level of understanding, it is an attempt to identify a mechanism for understanding groups of related remedies according to the natural classification of various sources used in homoeopathic practice (Scholten, 1993). This not only offers new aspects to well known remedies, but illuminates the smaller, less well known remedies, resulting in a more comprehensive and rounded understanding of the materia medica / M

Dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2007. / Until recently the most important method of studying homoeopathic remedies has been to look at each remedy separately and not in the context of a particular group to which it belongs. Group analysis, as defined by pioneering authors such as Sankaran (2002) and Scholten (1993), is an attempt to identify a mechanism for understanding groups of related remedies according to natural classification of the various sources used in homoeopathic practice. / M

This mini-dissertation was submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban Institute of Technology, 2005. xxvii, 153 p. / Chronic fatigue syndrome (CFS) remains a medically unexplained syndrome, with differing aetiological models, case definitions and treatment recommendations (Ranjith, 2005:13). Sharpe & Wessely (1997:179) state that the current case definition for CFS has assumed acceptance as representing nothing more than a working definition of a clinical problem, pending further understanding. CFS has subsequently become the focus of much research and debate (Wessely, Hotopf & Sharpe, 1999:13). Notwithstanding, the definition in terms of diagnostic criteria is adequate in meeting the needs of research studies (Rutherford, 2003). Anecdotal reports, espousing the effectiveness of homoeopathic treatment of CFS, points to the use of the similimum. (Bailey, 1995:189; De Schepper, 2001:6-7; Hardy, 2005:8-10). However, the limited research available on the subject suggests that more research needs to be conducted in this regard (Wessely, Hotopf & Sharpe, 1999:371; Walach, 2004:210-211). This double-blind placebo-controlled study was conducted to determine the effectiveness of homoeopathic similimum treatment in chronic fatigue syndrome (CFS). / M

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Technikon Natal, Durban, 2002. / The fungus Pycnoporus sanguineus was selected for this research project because of its similarity in appearance to a human kidney. It was initially thought that a connection to the Doctrine of Signatures could be proved, however, this was not the ultimate purpose of this research project. The purpose of this placebo-controlled investigation was to determine the effects of the thirtieth centesimal (30CH) potency of Pycnoporus sanguineus on individuals of average health; in order to discover the totality of symptoms produced by the remedy so that it may be prescribed according to the law of similars, as required by Homoeopathic science. It was hypothesised that this study would produce a list of symptoms associated with this substance, Pycnoporus sanguineus, which, can then be used Homoeopathically (according to the totality of symptoms produced by the drug so that it may be prescribed according to the law of similars) in the treatment of disease where no other remedy has yet acted precisely and thus be able to cure a class of cases that until then could only have been partially covered by existing remedies (Sherr 1994:58). This Homoeopathic drug proving of Pycnoporus sanguineus 30CH took the form of a double blind, placebo controlled trial on 30 subjects who met all the inclusion criteria. Fifty percent (15 of the 30) of the subjects received placebo in a randomised fashion, so that neither the provers nor the researcher knew who was receiving placebo or verum. As an added control measure, the provers were unaware of the substance, which they were proving or in which potency it was being proved. The study design consisted of two groups: one control group with placebo controls and the other experimental group, which also has intraindividual controls in which the prover serves as his or her own control i.e. the recorded state of the prover prior to the administration of the proving substance served as a control or baseline for comparison to the prover under the influence of the proving substance. (Stephenson 1960; Vithoulkas 1986:150). / M

El eje central del desarrollo de esta tesis lo constituye el trabajo elaborado a partir de la idea de vacío como concepto operativo; teniendo como principal objetivo experimentar operacionalmente la manera en que este podría ser visualizado por el espectador. A partir de la mezcla de diferentes materialidades y diversos medios (fotografía, video, instalación), las obras que a continuación se presentan buscan hacer visible diferentes estados de energía o densidades, que asociadas entre sí, permiten desestabilizar la noción de espacio y categorizarlo entre situaciones formales y dicotomías conceptuales tales como: visible/invisible, dentro/fuera, vacío/lleno, materia/no-materia, entre otras. La respuesta a la pregunta planteada inicialmente y que da origen a esta tesis, es paradójicamente su negación y superación, es decir, un encuentro de los límites que nunca llegan a colisionar del todo. Además se ha constatado que esto ocurre independientemente de la materialidad con la que se produce dicho vacío.

Mini-dissertation submitted in partial compliance with the requirements for a Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2008. / The purpose of this placebo controlled study was to evaluate the efficacy of a homoeopathic complex (Carbo Vegetabilis D9, Lycopodium clavatum D9, Nux Vomica D9 and Robinia Pseudoacacia D9) in the treatment of patients suffering from functional dyspepsia; in terms of the patient’s perception of the treatment. It was hypothesized that the patients treated with the complex would respond favorably in terms of the symptoms associated with dyspepsia. In this experimental study the single variable design was used for its ‘before and after with control’. Thirty patients with functional dyspepsia were selected after been screened according to diagnostic criteria identified by the researcher. These patients were divided into two groups according to simple random sampling. Data was collected at the Homoeopathic Day Clinic at the Durban University of Technology. Group one received the homoeopathic complex and group two received a placebo complex. Patients received treatment over a period of six weeks (three consultations). The patients, during each consultation, in the presence of the researcher, completed the Patient Perception Questionnaire. Results were statistically analysed using the FriedmansTest (inter group comparison) and The Wilcoxon signed Rank Test (intra group comparison). When the three questionnaires for each patient were compared it was found that neither the placebo group, nor the experimental group yielded significant improvement. Therefore the results of this clinical trial demonstrated that this homoeopathic complex is not effective in the treatment of functional dyspepsia, when compared to placebo, in terms of patient perception. / M

En el presente trabajo de investigación se evaluó el efecto antiinflamatorio y cicatrizante del extracto etanólico de hojas de Senna reticulata (Willd.)H.Irwin and Barneby “Retama” procedente del Departamento de San Martín (Tarapoto). Se determinaron los metabolitos secundarios mediante la marcha fitoquímica, identificando flavonoides, alcaloides, taninos, saponinas y glicósidos. Luego se efectuó el screening cromatográfico, para posteriormente realizar las lecturas al espectrofotómetro. Para la investigación farmacológica se preparó una crema base cold-cream a la cual se le añadió concentraciones de 5%, 10% y 20% del extracto, realizando el estudio antiinflamatorio y cicatrizante en ratones albinos de 25 a 30 g. Comparándose con Diclofenaco al 1% en gel para el efecto antiinflamatorio dando resultados no significativos. Mostró acción cicatrizante significativa confrontando con Neomicina-Bacitracina, glicina, L- cisteina, DL – treonina; obteniendo mayor efecto con la crema al 20% luego la crema al 10% y la crema al 5% del extracto etanólico. / In the present thesis there was evaluated the antiinflammatory and healing effect of the extract etanolic of leaves of Senna reticulata (Willd.) H Irwin and Barneby “Broom” proceeding from the departament of San Martín (Tarapoto). The secundary metabolitos were identified by phytochemistry procedure identifying flavonoids, alkaloids, tannins, saponines and glicosides. Then the chromatographic screening was effected later to realize the readings to the spectrophotometer. For the pharmacological investigation a cream was prepared base cold-cream to which were added concentrations of 5%, 10% and 20% of the extract, realizing the antiinflammatory and healing study in albino mice from 25 to 30 g. being compared by Diclofenaco to 1% in gel for the antiinflammatory effect giving not significant results. Showed healing significant action bordering with Neomicine – Bacitracine, glicine, L-cisteine, DL –treonine; obtaining major effect with the cream to 20% then the cream to 10% and the cream to 5% of the extract etanolic.

One third of the world’s population is estimated to be infected with M. tuberculosis, a pathogen which causes more human death and misery than any other bacterial disease. Whilst treatment is available, resistance to commonly used antimicrobials is a growing problem. Thus there is an urgent need to identify new compounds that can kill drug resistant isolates and are able to potentiate the activity of currently available antibiotics. The plant kingdom is a rich source of antibacterial compounds and a plant which has attracted particular interest is Humulus lupulus, more commonly known as the hop, which has been used as an antibacterial in beer for hundreds of years. Its antibacterial properties are thought to be due to the combined action of alpha and beta acids and polyphenols such as xanthohumol although the precise nature of their interactions and relative importance has yet to be determined. An optimised agar antimicrobial assay was developed and employed based on Mycobacterium smegmatis, to characterize the antibacterial activity of fifty commercially available hop varieties with a view to identifying novel antibacterial compounds. Surprisingly, no correlation was found between alpha and beta acid content and antibacterial activity. Chemical analysis of the most (Citra) and least (Galena) active hop variants using a combination of bioactivity based thin layer chromatography, mass spectrometry and HPLC revealed differences in the relative amounts of antimicrobial compounds such as humulone (alpha acid), lupulone (beta acid) and xanthohumol but failed to identify the presence of novel antibacterial compounds. Whilst no new antimicrobial compounds were identified, the Citra hop extract was able to potentiate the activity of the antibiotics imipenem and ciprofloxacin against clinical isolates of M. abscessus, a fast growing member of the mycobacterium family which infects individuals suffering from cystic fibrosis. The Citra hop extract also inhibited the growth drug resistant isolates of M. abscessus suggesting that it may have activity against other antibiotic resistant mycobacteria such as M. tuberculosis With regards to the mode of action, scanning electron microscopy revealed distinct changes to the outer cell structure of the bacteria, suggesting that hops contain compounds that interact with the bacterial cell membrane and/or cell wall. These changes were more profound in the presence of sub-inhibitory concentrations of imipenem, a compound which also targets the cell wall. Overall hops were shown to contain compounds which inhibited the growth of mycobacterium and were able to potentate the activity of antibiotics currently used to treat these pathogens. These findings suggest hops may be a fruitful source from which to isolate next generation compounds with which to treat increasingly drug resistant strains of mycobacteria.