3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item A bioactive association platform delivery system for enhanced efficacy of pharmaceutical products(2015) Braithwaite, Miles CharlesOral delivery of drugs is inundated by formulation challenges predominantly due to poor physicochemical properties of chemical entities resulting in anomalies in serum levels and inconsistent pharmacokinetics and pharmacodynamics. Similar challenges exist for nutraceutical products however, there has been a recent shift in research paradigms towards novel formulation strategies to render these agents invaluable complementary treatments. In this view, vitamin D has gained interest, however it’s effective therapeutic use is limited by low aqueous solubility, erratic inter-patient response, and inadequate formulation design. Cholecalciferol (D3), being a potent form of the vitamin, is widely supplemented and prescribed and was selected as the model agent for proof of concept in the design of a novel oral Drug Delivery System (DDS) in the current research. An ideal physiological milieu is often essential for intended performance of even advanced DDS’s. GIT topology may have an even greater impact on modified dosage forms compared to conventional dosage forms. The use of absorption and solubility enhancers is a tried and tested formulation strategy to improve bioavailability and efficacy of drugs with unfavourable physicochemical characteristics. Despite being an integral part of modern formulation design, these bioenhancers may prove only marginally effective in oral delivery unless the physiological state is considered during formulation. It was therefore imperative that the DDS designed in this investigation included measures to mitigate this effect and achieve robust efficacy regardless of the dynamic GIT condition. In addition, most nutraceuticals typically occur as multicomponent products, yet different combined BCS class vitamins may encounter erratic absorption due to differences in solubility and flocculation effects that impede dispersion in aqueous media. It is therefore imperative to formulate and evaluate a DDS containing more than one nutraceutical agent for greater “real-world” relevance instead of a single vitamin DDS formulation that has been pursued in past studies. The current work therefore set out to develop a DDS capable of orally delivering multiple nutraceutical actives and biological constituents from a single formulation framework with modifiable release kinetics and a unified release of synergistic vitamins, with D3 as the focus agent for enhanced oral bioavailability. Few researchers have investigated the use of multiple biological enhancers combined with synthetic carriers in a dosage form to aid nutraceutical deliveryItem A laboratory model for studying inhalation therapy in traditional healing rites(2008-06-04T11:58:18Z) Braithwaite, Miles CharlesABSTRACT The burning of selected indigenous plants and the inhalation of the smoke liberated from them has been a widely accepted and practised form of administration in traditional healing therapy dating back to as far as the Koi and San, and is a method still widely practised in South Africa today. Inhalation has various advantages as a method of administration in both allopathic and traditional practices. Not only is inhalation a highly effective mode of administration because of its direct and local effect on the lungs for the treatment of respiratory ailments, but also because of its ability to deliver drugs effectively systemically. This study elucidated the rationale behind this widely practised treatment by examining chromatographic and antimicrobial data. Five plants that are commonly administered traditionally through inhalation were chosen: Heteropyxis natalensis, Myrothamnus flabellifolius, Artemisia afra, Pellaea calomelanos, and Tarchonanthus camphoratus. An apparatus was designed and constructed and the burning process that occurs in the traditional setting was simulated with the selected plants. The induced volatile fraction (smoke) was captured for analysis. Control solvent extracts were made for each plant using conventional extraction solvents, methanol, acetone, water, and the essential oil of the aromatic plants was also investigated. Antimicrobial assays revealed that the extracts (smoke) obtained after burning had lower minimum inhibitory concentration (MIC) values than the corresponding solvent extracts in most cases. For Klebsiella pneumoniae all five inhalation samples were far more active than the conventional extracts. When tested against the pathogen B. cereus, M. flabellifolius and P. calomelanos inhalation samples proved to exhibit superior antimicrobial activity compared to the respective solvent extracts. Pellaea calomelanos inhalation extract had the lowest MIC values compared to the solvent extracts for all pathogens (P. calomelanos inhalation extract MIC values: 0.53; 1.00; 0.53; 0.53 mg/ml for S. aureus, B. cereus, K. pneumoniae and C. neoformans respectively). Inhalation extracts exhibited different chemical profiles from the solvent extracts of the same plant. For example, A. afra inhalation extract had an abundance of peaks at various retention times from 3.2 to 5.4 minutes, which were not present in the chromatograms of the acetone and methanol extracts of the same plant. These results, albeit preliminary, suggest that the chemistry and antimicrobial activity of plants are influenced by the combustion process which is often used in traditional healing rites.