Sildenafil citrate (SC) is a phosphodiesterase-5 inhibitor that is used to treat pulmonary hypertension (PH) in paediatric patients. The purpose of these studies was to develop a formulation and manufacture an orodispersible tablet (ODT) that can be easily administered to neonates and children with PH. The advantages of ODT dosage forms include ease of administration, rapid dissolution of the API, SC. Furthermore the dosage form can be taken without water which is beneficial to patients without immediate access to potable fluids. A simple, rapid, accurate, precise and selective reversed-phase HPLC method was developed and validated in accordance with International Conference on Harmonization (ICH) guidelines and was successfully used for the analysis of SC as raw material and in SC containing pharmaceutical dosage forms. Preformulation studies were performed on SC, alone and in combination with potential excipients that could be used to make tablets. Investigations into potential interactions between SC and the excipients were performed using Differential Scanning Calorimetry (DSC) and Infrared Spectroscopy (IR). DSC results revealed that SC was compatible with all potential excipients except mannitol and magnesium stearate. However these interactions were not observed with IR and therefore it was concluded that the interactions were induced by the high temperatures that DSC operates at. Particle size and shape was also established by use of Scanning Electron Microscopy (SEM) and flow properties were monitored by calculating Carr’s Index (CI) and the Hausner Ratio (HR). Direct compression was used as the method of manufacture for SC tablets as this approach is simple and the most economic production approach. The powder blends were assessed for bulk and tapped density and the CI and HR were used to determine the flowability of the blends. The quality attributes of the resultant tablets that were monitored included uniformity of weight, friability, crushing strength, tensile strength, disintegration, wetting and in vitro dispersion times. Design of Experiments is an efficient statistical approach that has become a popular tool used in the pharmaceutical industry to optimize formulation compositions, as it allows for the investigation of several input factors at the same time whilst not using the tedious and traditional “ modification of one variable at a time” approach. A Central composite experimental design was chosen as the most appropriate means to optimize the formulation as it produces more accurate results as opposed to other experimental designs approaches as input factors are investigated at five different levels. Through the use of mathematical modelling, optimum concentrations of disintegrant(s) and an appropriate blending time were established. Analysis of the data from the experimental design and mathematical modelling studies reveal that no changes in disintegrant concentration or blending time altered the disintegration time of the formulation to any significant extent. This result is most likely due to the fact that the critical disintegrant concentration has been reached and increasing the disintegrant concentration further has no effect on disintegration time. It was also established that a change in the concentration of CMS and CRP altered the wetting time of the tablet significantly. Finally it was noted that there was a linear relationship between blending time and the uniformity of content of the tablets produced in these studies. The optimized product was a white tablet with a diameter of 7.31 mm with a thickness of 2.80mm.The dosage form had no visible cracks or evidence of picking or sticking. The tablet exhibits suitable friability and tensile strength while exhibiting a disintegration time of only 8s. Therefore an orodispersible tablet containing SC intended for paediatric use has been successfully developed, manufactured and optimized through the use of preformulation studies, appropriate quality control monitoring and mathematical modelling. These formulations require further optimization in respect of addition of flavours and or additional sweetening agents.

Based on oral histories of agriculture and health in the Mae Chaem valley, northern Thailand, this work documents changing child health and medical practice since the 1950's and explores possible connections with increasing pesticide use. The research shows how local knowledge can help us understand relationships between changing technology, ecology, and human health. Parents and farmers in the Mae Chaem valley of Chiang Mai province, Northern Thailand, live at the intersection of multiple local and global streams of land use and child health biotechnology. Based on systematically collected autobiographical oral histories from parents and farmers, as well as interviews and participant observation with land use and child health experts the study considers the relationships between child health and land use change, and particularly the rise of pesticide intensive cash cropping, since the late 1950’s. Introductory chapters on theory and methods precede a description of the ethnographic context. Case studies illustrating parent and farmer histories of child health and land use change spanning fifty years are provided. Seven streams of biotechnical expertise are identified, and mini-ethnographies are provided for each including domestic, Buddhist, Muang, spirit, market, national, and Christian. These seven streams are analyzed using actor-network theory (ANT) with relationships to particular notions of ontology, cosmology, and ecology. Results demonstrate the ongoing importance of parents and farmers as decision making agents at the intersection of multiple and competing cultural and biotechnical streams, even where they face efforts by large multinational corporations or other agencies to advertise, constrain and monopolize local biotechnical choice. Within the fifty year time period under consideration, the oral histories describe particular child health and land use trends. These locally perceived trends provide challenging perspectives on the relationship between ‘development’ and child health in Thailand. While children die far less often now than in the past, oral histories suggest that both children and fields now suffer from more kinds of illness, and more often, than before. In particular, both qualitative and more quantitative analysis suggests differences in the experience of child health among pesticide and non-pesticide using households.

Based on oral histories of agriculture and health in the Mae Chaem valley, northern Thailand, this work documents changing child health and medical practice since the 1950's and explores possible connections with increasing pesticide use. The research shows how local knowledge can help us understand relationships between changing technology, ecology, and human health. Parents and farmers in the Mae Chaem valley of Chiang Mai province, Northern Thailand, live at the intersection of multiple local and global streams of land use and child health biotechnology. Based on systematically collected autobiographical oral histories from parents and farmers, as well as interviews and participant observation with land use and child health experts the study considers the relationships between child health and land use change, and particularly the rise of pesticide intensive cash cropping, since the late 1950’s. Introductory chapters on theory and methods precede a description of the ethnographic context. Case studies illustrating parent and farmer histories of child health and land use change spanning fifty years are provided. Seven streams of biotechnical expertise are identified, and mini-ethnographies are provided for each including domestic, Buddhist, Muang, spirit, market, national, and Christian. These seven streams are analyzed using actor-network theory (ANT) with relationships to particular notions of ontology, cosmology, and ecology. Results demonstrate the ongoing importance of parents and farmers as decision making agents at the intersection of multiple and competing cultural and biotechnical streams, even where they face efforts by large multinational corporations or other agencies to advertise, constrain and monopolize local biotechnical choice. Within the fifty year time period under consideration, the oral histories describe particular child health and land use trends. These locally perceived trends provide challenging perspectives on the relationship between ‘development’ and child health in Thailand. While children die far less often now than in the past, oral histories suggest that both children and fields now suffer from more kinds of illness, and more often, than before. In particular, both qualitative and more quantitative analysis suggests differences in the experience of child health among pesticide and non-pesticide using households.

Based on oral histories of agriculture and health in the Mae Chaem valley, northern Thailand, this work documents changing child health and medical practice since the 1950's and explores possible connections with increasing pesticide use. The research shows how local knowledge can help us understand relationships between changing technology, ecology, and human health. Parents and farmers in the Mae Chaem valley of Chiang Mai province, Northern Thailand, live at the intersection of multiple local and global streams of land use and child health biotechnology. Based on systematically collected autobiographical oral histories from parents and farmers, as well as interviews and participant observation with land use and child health experts the study considers the relationships between child health and land use change, and particularly the rise of pesticide intensive cash cropping, since the late 1950’s. Introductory chapters on theory and methods precede a description of the ethnographic context. Case studies illustrating parent and farmer histories of child health and land use change spanning fifty years are provided. Seven streams of biotechnical expertise are identified, and mini-ethnographies are provided for each including domestic, Buddhist, Muang, spirit, market, national, and Christian. These seven streams are analyzed using actor-network theory (ANT) with relationships to particular notions of ontology, cosmology, and ecology. Results demonstrate the ongoing importance of parents and farmers as decision making agents at the intersection of multiple and competing cultural and biotechnical streams, even where they face efforts by large multinational corporations or other agencies to advertise, constrain and monopolize local biotechnical choice. Within the fifty year time period under consideration, the oral histories describe particular child health and land use trends. These locally perceived trends provide challenging perspectives on the relationship between ‘development’ and child health in Thailand. While children die far less often now than in the past, oral histories suggest that both children and fields now suffer from more kinds of illness, and more often, than before. In particular, both qualitative and more quantitative analysis suggests differences in the experience of child health among pesticide and non-pesticide using households. / Arts, Faculty of / Anthropology, Department of / Graduate