The South African coastal and marine environment is an essential ecologic and economic asset. Its associated services and products are substantially contributing to economic growth and sustainable development of the country. However, it is internationally and nationally recognised that land-based marine pollution (LBMP) is the most important single risk to the health and sustainability of coastal and marine waters and the associated ecosystems. The regulation of LBMP at the national level is still difficult and challenging. The issue of LBMP management has only recently been introduced in South Africa with the development of the National Programme of Action to Protect Marine Environment from Land-based Activities, 2008. South Africa is only starting to consider the question of LBMP regulation. This thesis aims to conduct a critical analysis of the South African regulatory framework pertaining to LBMP in comparison to international best practice and the French regulatory framework, in order to identify the key South African challenges in this regard and to make recommendations to address them. In order to do so, this research commences by providing an analysis of LBMP and the theoretical foundations associated with LBMP regulation, as promoted by international best practice. The study identifies and assesses the main regulatory features to be considered in the development, implementation and/or assessment of a regulatory framework pertaining to LBMP. These features will form the methodological framework to conduct the comparative legal assessment between the French and South African regulatory frameworks pertaining to LBMP. This thesis then provides a detailed and thorough legal analysis of the French and South African regulatory frameworks pertaining to LBMP using the methodological framework developed using guidance from international best practice. Finally, based on lessons learnt from the comparative legal study, this study concludes with a set of recommendations for the South African context. / Thesis (LL.D.)--North-West University, Potchefstroom Campus, 2011.

The South African coastal and marine environment is an essential ecologic and economic asset. Its associated services and products are substantially contributing to economic growth and sustainable development of the country. However, it is internationally and nationally recognised that land-based marine pollution (LBMP) is the most important single risk to the health and sustainability of coastal and marine waters and the associated ecosystems. The regulation of LBMP at the national level is still difficult and challenging. The issue of LBMP management has only recently been introduced in South Africa with the development of the National Programme of Action to Protect Marine Environment from Land-based Activities, 2008. South Africa is only starting to consider the question of LBMP regulation. This thesis aims to conduct a critical analysis of the South African regulatory framework pertaining to LBMP in comparison to international best practice and the French regulatory framework, in order to identify the key South African challenges in this regard and to make recommendations to address them. In order to do so, this research commences by providing an analysis of LBMP and the theoretical foundations associated with LBMP regulation, as promoted by international best practice. The study identifies and assesses the main regulatory features to be considered in the development, implementation and/or assessment of a regulatory framework pertaining to LBMP. These features will form the methodological framework to conduct the comparative legal assessment between the French and South African regulatory frameworks pertaining to LBMP. This thesis then provides a detailed and thorough legal analysis of the French and South African regulatory frameworks pertaining to LBMP using the methodological framework developed using guidance from international best practice. Finally, based on lessons learnt from the comparative legal study, this study concludes with a set of recommendations for the South African context. / Thesis (LL.D.)--North-West University, Potchefstroom Campus, 2011.

Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is effective against drug-resistant Plasmodium falciparum strains and is of significance in the current antimalarial campaign. As formulating an ACT double fixed-dose combination is technically difficult, it is essential that fixed-dose combinations are shown to have satisfactory ingredient compatibility, stability, and dissolution rates similar to the separate oral dosage forms. Since the general deployment of a combination of artesunate and mefloquine in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of Plasmodium falciparum malaria in the experimental studies (Nosten et al., 2000:297; WHO, 2010:17). However, the successful formulation of a solid oral dosage form and fixed dosage combination of artesunate and mefloquine remains both a market opportunity and a challenge. Artesunate and mefloquine both exhibited poor flow properties. Furthermore, different elimination half-lives, treatment dosages as well as solubility properties of artesunate and mefloquine required different formulation approaches. To substantiate the FDA’s pharmaceutical quality by design concept, the double fixed-dose combination of artesunate and mefloquine required strict preliminary formulation considerations regarding compatibility between excipients and between the APIs. Materials and process methods were only considered if theoretically and experimentally proved safe. Infrared absorption spectroscopy (IR) and X-ray powder diffraction (XRPD) data proved compatibility between ingredients and stability during the complete manufacturing process by a peak by peak correlation. Scanning Electron Micrographs (SEM) provided explanations for the inferior flow properties exhibited by the investigated APIs. Particle size analysis and SEM micrographs confirmed that the larger, rounder and more consistently sized particles of the granulated APIs contributed to improved flow under the specified testing conditions. A compressible mixture containing 615 mg of the APIs in accordance with the WHO recommendation of 25 mg/kg of mefloquine taken in two or three divided dosages, and 4 mg/kg/day for 3 days of artesunate for uncomplicated falciparum malaria was developed. Mini-tablets of artesunate and mefloquine were compressed separately and successfully with the required therapeutic dosages and complied with pharmacopoeial standards. Preformulation studies eventually led to a formula for a double fixed-dose combination and with the specific aim of delaying the release of artesunate due to its short half-life. A factorial design revealed the predominant factors contributing to the successful wet granulation of artesunate and mefloquine. A fractional factorial design identified the optimum factors and factor levels. The application of the granulation fluid (20% w/w) proved to be sufficient by a spraying method for both artesunate and mefloquine. A compatible acrylic polymer and coating agent for artesunate, Eudragit® L100 was employed to delay the release of approximately half of the artesunate dose from the double fixed-dose combination tablet until a pH of 6.8. A compressible mixture was identified and formulated to contain 200 mg of artesunate and 415 mg of mefloquine per tablet. The physical properties of the tablets complied with BP standards. An HPLC method from available literature was adapted and validated for analytical procedures. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the double fixed-dose combination. The initial dissolution rate (DRi) of artesunate and mefloquine in the acidic dissolution medium was rapid as required. The enteric coated fraction of the artesunate exhibited no release in an acidic environment after 2 hours, but rapid release in a medium with a pH of 6.8. The structure of the granulated particles of mefloquine may have contributed to its first order release profile in the dissolution mediums. A linear correlation was present between the rate of mefloquine release and the percentage of mefloquine dissolved (R2 = 0.9484). Additionally, a linear relationship was found between the logarithm of the percentage mefloquine remaining against time (R2 = 0.9908). First order drug release is the dominant release profile found in the pharmaceutical industry today and is coherent with the kinetics of release obtained for mefloquine. A concept pre-clinical phase, double fixed-dose combination solid oral dosage form for artesunate and mefloquine was developed. The double fixed-dose combination was designed in accordance with the WHO’s recommendation for an oral dosage regimen of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. The specifications of the double fixed-dose combination were developed in close accordance with the FDA’s quality by design concept and WHO recommendations. An HPLC analytical procedure was developed to verify the presence of artesunate and mefloquine. The dissolution profiles of artesunate and mefloquine were investigated during the dissolution studies. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

In terms of section 186(1)(e) of the Labour Relations Act 66 of 1995 constructive dismissal occurs where an employee terminated a contract of employment with or without notice because the employer made continued employment intolerable. Work stress is becoming more and more imminent in the workplace. Some employees feel that the amount of work stress also makes their continued employment intolerable, and then they claim constructive dismissal. This raises the question whether the courts should apply the same tests they apply in constructive dismissal cases as well as in cases where the employee resigns because of work stress. But, if the same tests that are used to determine if there has been a constructive dismissal are used in a case where an employee resigns because of work stress, a real danger exists because then it can lead to the misuse of a claim of constructive dismissal by employees who cannot handle a minimum amount of work stress. Over the years the courts have indicated that they apply an objective test in cases of constructive dismissal. This leads to the argument whether subjectivity should play a role, and whether one should look at the subjective perspective of both the employer and the employee. This research looks at numerous court decisions, from both the South African legal system as well as the United Kingdom legal system, in order to determine which tests the South African courts need to apply when they are confronted with a constructive dismissal claim where the employee resigned due to work stress. Constructive dismissal – resignation – work stress – stress due to an excessive workload – work stress and employee wellness – stress based claims. / Thesis (LL.M. (Labour Law))--North-West University, Potchefstroom Campus, 2011

Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is effective against drug-resistant Plasmodium falciparum strains and is of significance in the current antimalarial campaign. As formulating an ACT double fixed-dose combination is technically difficult, it is essential that fixed-dose combinations are shown to have satisfactory ingredient compatibility, stability, and dissolution rates similar to the separate oral dosage forms. Since the general deployment of a combination of artesunate and mefloquine in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of Plasmodium falciparum malaria in the experimental studies (Nosten et al., 2000:297; WHO, 2010:17). However, the successful formulation of a solid oral dosage form and fixed dosage combination of artesunate and mefloquine remains both a market opportunity and a challenge. Artesunate and mefloquine both exhibited poor flow properties. Furthermore, different elimination half-lives, treatment dosages as well as solubility properties of artesunate and mefloquine required different formulation approaches. To substantiate the FDA’s pharmaceutical quality by design concept, the double fixed-dose combination of artesunate and mefloquine required strict preliminary formulation considerations regarding compatibility between excipients and between the APIs. Materials and process methods were only considered if theoretically and experimentally proved safe. Infrared absorption spectroscopy (IR) and X-ray powder diffraction (XRPD) data proved compatibility between ingredients and stability during the complete manufacturing process by a peak by peak correlation. Scanning Electron Micrographs (SEM) provided explanations for the inferior flow properties exhibited by the investigated APIs. Particle size analysis and SEM micrographs confirmed that the larger, rounder and more consistently sized particles of the granulated APIs contributed to improved flow under the specified testing conditions. A compressible mixture containing 615 mg of the APIs in accordance with the WHO recommendation of 25 mg/kg of mefloquine taken in two or three divided dosages, and 4 mg/kg/day for 3 days of artesunate for uncomplicated falciparum malaria was developed. Mini-tablets of artesunate and mefloquine were compressed separately and successfully with the required therapeutic dosages and complied with pharmacopoeial standards. Preformulation studies eventually led to a formula for a double fixed-dose combination and with the specific aim of delaying the release of artesunate due to its short half-life. A factorial design revealed the predominant factors contributing to the successful wet granulation of artesunate and mefloquine. A fractional factorial design identified the optimum factors and factor levels. The application of the granulation fluid (20% w/w) proved to be sufficient by a spraying method for both artesunate and mefloquine. A compatible acrylic polymer and coating agent for artesunate, Eudragit® L100 was employed to delay the release of approximately half of the artesunate dose from the double fixed-dose combination tablet until a pH of 6.8. A compressible mixture was identified and formulated to contain 200 mg of artesunate and 415 mg of mefloquine per tablet. The physical properties of the tablets complied with BP standards. An HPLC method from available literature was adapted and validated for analytical procedures. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the double fixed-dose combination. The initial dissolution rate (DRi) of artesunate and mefloquine in the acidic dissolution medium was rapid as required. The enteric coated fraction of the artesunate exhibited no release in an acidic environment after 2 hours, but rapid release in a medium with a pH of 6.8. The structure of the granulated particles of mefloquine may have contributed to its first order release profile in the dissolution mediums. A linear correlation was present between the rate of mefloquine release and the percentage of mefloquine dissolved (R2 = 0.9484). Additionally, a linear relationship was found between the logarithm of the percentage mefloquine remaining against time (R2 = 0.9908). First order drug release is the dominant release profile found in the pharmaceutical industry today and is coherent with the kinetics of release obtained for mefloquine. A concept pre-clinical phase, double fixed-dose combination solid oral dosage form for artesunate and mefloquine was developed. The double fixed-dose combination was designed in accordance with the WHO’s recommendation for an oral dosage regimen of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. The specifications of the double fixed-dose combination were developed in close accordance with the FDA’s quality by design concept and WHO recommendations. An HPLC analytical procedure was developed to verify the presence of artesunate and mefloquine. The dissolution profiles of artesunate and mefloquine were investigated during the dissolution studies. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

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.

In terms of section 186(1)(e) of the Labour Relations Act 66 of 1995 constructive dismissal occurs where an employee terminated a contract of employment with or without notice because the employer made continued employment intolerable. Work stress is becoming more and more imminent in the workplace. Some employees feel that the amount of work stress also makes their continued employment intolerable, and then they claim constructive dismissal. This raises the question whether the courts should apply the same tests they apply in constructive dismissal cases as well as in cases where the employee resigns because of work stress. But, if the same tests that are used to determine if there has been a constructive dismissal are used in a case where an employee resigns because of work stress, a real danger exists because then it can lead to the misuse of a claim of constructive dismissal by employees who cannot handle a minimum amount of work stress. Over the years the courts have indicated that they apply an objective test in cases of constructive dismissal. This leads to the argument whether subjectivity should play a role, and whether one should look at the subjective perspective of both the employer and the employee. This research looks at numerous court decisions, from both the South African legal system as well as the United Kingdom legal system, in order to determine which tests the South African courts need to apply when they are confronted with a constructive dismissal claim where the employee resigned due to work stress. Constructive dismissal – resignation – work stress – stress due to an excessive workload – work stress and employee wellness – stress based claims. / Thesis (LL.M. (Labour Law))--North-West University, Potchefstroom Campus, 2011

Although these discourses construct disability differently, three of them – the lay, charity and medical discourses – view disability very negatively. The lay discourse sees disability as something to be fearful of and therefore chooses to ignore it. According to the charity discourse people who are disabled should be pitied and helped because they are dependent and helpless. The medical discourse defines disability as abnormal – a “sickness” that requires treatment by medical experts. This study endeavors to challenge the stereotypical “picture” of a person with a disability. By conducting a narrative research design the life-world of a unique boy (who has a physical disability, called spina bifida) is captured in the telling of his life-story. A narrative research design was specifically chosen to portray the context and life-experiences (good and bad) of this little boy – a child in totality. The narrative life-story was written in the first person in order to invite the reader as a co-participant into the world of a boy with spina bifida. An asset-based approach accompanied the narrative research design in order to explore whether positive aspects of this boy’s life-world could be identified. Where disability is concerned, the asset-based approach proposes a shift from the traditional “deficit approach” towards a “strength-based approach”. This study not only tells the captivating life-story of a boy with a physical disability, but also identifies and embraces the positive side of living with a disability. / Dissertation (MEd (Educational Psychology))--University of Pretoria, 2006. / Educational Psychology / unrestricted

The aim of this study is to explore the assets that are available in the context of the school of industries that will promote the youth at risk’s psycho-social development using the asset based approach. The researcher followed a qualitative research approach guided by an interpretivist epistemology and employed a case study design in the natural environment. Multiple data collection methods (interviews, focus groups and documentation) were used in order to gain rich descriptions of the participants’ perceptions of assets available for the enhancement of the adolescent’s psycho-social development. Results indicate that many assets for example, human as well as physical resources, structures and procedures are currently used and can be effectively mobilized in the future at schools of industries to promote the development of the adolescent on personal, social and moral levels. Placement at a school of industries is beneficial to the youth at risk because he can continue his schooling and therapeutic counseling is available which will empower him to successfully return to the community. Dysfunctions in the system involved with the placement of youth at risk at schools of industries are currently preventing the use of the school of industries, involved in this research, as a community asset for the child- and youth care system. Copyright / Dissertation (MEd)--University of Pretoria, 2009. / Educational Psychology / unrestricted