Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

South Africa’s electricity supply is under pressure. Mining is one of South Africa’s largest electricity consumers with electricity-intensive services such as compressed air, cooling, ventilation, etc. More than 40% of mine electricity consumption is used for cooling and ventilation. There is a need to reduce the operational cost on a mine as electricity prices are set to increase at least 2% above South Africa’s inflation target. The mine-cooling and ventilation system was investigated for energy cost-saving. No clear energy and cost-saving strategy for the entire mine-cooling and ventilation system was found. Projects are implemented ad hoc and scattered throughout the system. A strategy is needed to help realise the total saving available on the entire mine-cooling and ventilation system. An implementation strategy for load-management and energy-saving projects on a mine-cooling and ventilation system was developed. A peak clip project on the surface BAC was developed and added to the strategy. The resultant strategy attains all savings throughout the entire mine-cooling and ventilation system. A peak clip project on the surface BAC of a typical mine results in an annual saving of R1.4 million. Implementing this new project on other mines could save R11 million annually. Implementing the sequenced combination of cooperative projects on a typical mine results in a saving of R30 million. That is a saving of 38% on the ventilation and cooling cost and 16% on the total mine electricity bill. / PhD (Mechanical Engineering), North-West University, Potchefstroom Campus, 2014

South Africa’s electricity supply is under pressure. Mining is one of South Africa’s largest electricity consumers with electricity-intensive services such as compressed air, cooling, ventilation, etc. More than 40% of mine electricity consumption is used for cooling and ventilation. There is a need to reduce the operational cost on a mine as electricity prices are set to increase at least 2% above South Africa’s inflation target. The mine-cooling and ventilation system was investigated for energy cost-saving. No clear energy and cost-saving strategy for the entire mine-cooling and ventilation system was found. Projects are implemented ad hoc and scattered throughout the system. A strategy is needed to help realise the total saving available on the entire mine-cooling and ventilation system. An implementation strategy for load-management and energy-saving projects on a mine-cooling and ventilation system was developed. A peak clip project on the surface BAC was developed and added to the strategy. The resultant strategy attains all savings throughout the entire mine-cooling and ventilation system. A peak clip project on the surface BAC of a typical mine results in an annual saving of R1.4 million. Implementing this new project on other mines could save R11 million annually. Implementing the sequenced combination of cooperative projects on a typical mine results in a saving of R30 million. That is a saving of 38% on the ventilation and cooling cost and 16% on the total mine electricity bill. / PhD (Mechanical Engineering), North-West University, Potchefstroom Campus, 2014

Because the development of resources in any language is an expensive process, many languages, including the indigenous languages of South Africa, can be classified as being resource scarce, or lacking in tagging resources. This study investigates and applies techniques and methodologies for optimising the use of available resources and improving the accuracy of a tagger using Afrikaans as resource-scarce language and aims to i) determine whether combination techniques can be effectively applied to improve the accuracy of a tagger for Afrikaans, and ii) determine whether structural semi-supervised learning can be effectively applied to improve the accuracy of a supervised learning tagger for Afrikaans. In order to realise the first aim, existing methodologies for combining classification algorithms are investigated. Four taggers, trained using MBT, SVMlight, MXPOST and TnT respectively, are then combined into a combination tagger using weighted voting. Weights are calculated by means of total precision, tag precision and a combination of precision and recall. Although the combination of taggers does not consistently lead to an error rate reduction with regard to the baseline, it manages to achieve an error rate reduction of up to 18.48% in some cases. In order to realise the second aim, existing semi-supervised learning algorithms, with specific focus on structural semi-supervised learning, are investigated. Structural semi-supervised learning is implemented by means of the SVD-ASO-algorithm, which attempts to extract the shared structure of untagged data using auxiliary problems before training a tagger. The use of untagged data during the training of a tagger leads to an error rate reduction with regard to the baseline of 1.67%. Even though the error rate reduction does not prove to be statistically significant in all cases, the results show that it is possible to improve the accuracy in some cases. / MSc (Computer Science), North-West University, Potchefstroom Campus, 2015

Because the development of resources in any language is an expensive process, many languages, including the indigenous languages of South Africa, can be classified as being resource scarce, or lacking in tagging resources. This study investigates and applies techniques and methodologies for optimising the use of available resources and improving the accuracy of a tagger using Afrikaans as resource-scarce language and aims to i) determine whether combination techniques can be effectively applied to improve the accuracy of a tagger for Afrikaans, and ii) determine whether structural semi-supervised learning can be effectively applied to improve the accuracy of a supervised learning tagger for Afrikaans. In order to realise the first aim, existing methodologies for combining classification algorithms are investigated. Four taggers, trained using MBT, SVMlight, MXPOST and TnT respectively, are then combined into a combination tagger using weighted voting. Weights are calculated by means of total precision, tag precision and a combination of precision and recall. Although the combination of taggers does not consistently lead to an error rate reduction with regard to the baseline, it manages to achieve an error rate reduction of up to 18.48% in some cases. In order to realise the second aim, existing semi-supervised learning algorithms, with specific focus on structural semi-supervised learning, are investigated. Structural semi-supervised learning is implemented by means of the SVD-ASO-algorithm, which attempts to extract the shared structure of untagged data using auxiliary problems before training a tagger. The use of untagged data during the training of a tagger leads to an error rate reduction with regard to the baseline of 1.67%. Even though the error rate reduction does not prove to be statistically significant in all cases, the results show that it is possible to improve the accuracy in some cases. / MSc (Computer Science), North-West University, Potchefstroom Campus, 2015