http://hdl.handle.net/10394/1 2017-07-09T18:02:43Z 2017-07-09T18:02:43Z Scholtz, Jacques Coenraad http://hdl.handle.net/10394/25117 2017-07-06T16:02:02Z 2016-01-01T00:00:00Z

Prediction of compressibility of pharmaceutical excipients in solid oral dosage forms Scholtz, Jacques Coenraad Tablets are one of the most preferred dosage forms for patients, but pre-formulation studies for tablets are often time consuming and expensive. The SeDeM Expert Diagram System attempts to address this problem by decreasing the amount of experiments required to develop an acceptable direct compression tablet formulation. This is done by processing and interpreting data obtained from known techniques already widely in use in the pharmaceutical industry to characterise active pharmaceutical ingredients (API’s) and excipients. In this study, the prediction ability of the SeDeM Expert Diagram System with a special focus on testing the limits of the system was investigated. Three different API’s with different direct compression properties (i.e. paracetamol, furosemide and pyridoxine) as well as seven excipients representing different classes and types of widely used direct compression excipients (i.e. Tablettose® 80, FlowLac® 100, Avicel® PH200, Emcompress®, Cellactose® 80, MicroceLac® 100 and StarLac®) were selected and characterised by applying the SeDeM Expert Diagram System. Predicted formulations were tableted and evaluated according to the set criteria. If a tablet formulation failed to meet the criteria, the ratio of excipient to API was increased in 5 % w/w increments until a successful formulation was obtained, whereas the reverse was applied if a formulation was successful to determine failure point. The SeDeM Expert Diagram System proved to be proficient at predicting acceptable tablet formulations, with a few exceptions. This was specifically the case where paracetamol and furosemide were concerned as well as some excipients. While SeDeM predicted that paracetamol would only be able to deliver acceptable tablets with three excipients (i.e. FlowLac® 100, Avicel® PH200 and StarLac®), all the selected excipients were in fact able to create acceptable direct compression tablets. When all the paracetamol formulations were considered, tablet failure most often occurred due to capping. However, the reason for failure of the novel direct-compression excipients (i.e. Cellactose® 80, MicroceLac® 100 and StarLac®) was due to problems other than capping. In the case of furosemide, the limits of five parameters were not met, including particle size limits, powder flow as well as the cohesion index. The SeDeM System was unable to successfully predict any furosemide direct-compression tablet formulations because the powder mixtures exhibited poor powder flow properties. This can be explained by the fact that furosemide has very small particles, which coated the excipient particle surfaces and thereby formed interactive powder mixtures, which was confirmed with the use of SEM microscopy. SeDeM was able to correctly predict five of the seven selected excipients for successful directcompression tablet formulations for pyridoxine within an acceptable margin of error. Only two excipients (Emcompress® and Cellactose® 80) performed better than expected by the SeDeM System. From the results of this study it is evident that certain physicochemical properties of API’s such as elasticity and cohesive behaviour are not compensated for or compensated for sufficiently by the SeDeM System. Furthermore, some novel direct-compression excipients (e.g. co-processed excipients) proved to exceed the SeDeM Expert Diagram Systems’ expectations and predictions to correct for API failure to produce direct compressible tablets PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2017

2016-01-01T00:00:00Z Wentzel, Annemarie http://hdl.handle.net/10394/25116 2017-07-06T13:01:22Z 2016-01-01T00:00:00Z

Electrical and cardiac stress reactivity associations with pre-clinical target organ damage : the SABPA study Wentzel, Annemarie Motivation: People’s physiological adaptive responses to chronic stressful environments have been persistently associated with an increased incidence of cardiovascular diseases (CVD) and co-morbidities. An inability to successfully respond to both mental and physical stressors is associated with an increased incidence of hypertension, coronary artery disease (CAD), stroke and cardiac structural remodelling. These adaptive responses not only depend on one’s personality and previous experiences, but also on factors such as age, gender and ethnicity. The link between cardiovascular risk and the development of CVD may be presented by reactivity of the autonomic nervous system (ANS), such as during acute mental stress application, and may accompany specific reactivity patterns. It has been demonstrated that during acute mental stress exposure, urban-dwelling Blacks (hereafter referred to as Africans) present elevated blood pressure (BP) values and exhibit α-adrenergic vascular responses, whilst their White (hereafter referred to as Caucasian) counterparts predominantly presented a central cardiac, β-adrenergic response accompanied by essentially normal BP values. Therefore, an increased cardiovascular risk may be linked to α-adrenergic vascular responses in those experiencing greater stress. However, whether these specific haemodynamic responses are linked to identifiable cardiac stress and electrical reactivity markers during acute mental stress has yet to be determined. Markers of cardiac stress include cardiac troponin T (cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP). These markers are traditionally used to indicate cardiac hypertrophy, ischemia and heart failure. However, recently increased levels of these markers have been associated with disrupted autonomic function and acute mental stress. Electrical markers pertaining to cardiac autonomic function, such as the corrected QT interval (QTc), may also indicate autonomic alterations during acute mental stress, seeing that the QTc has been shown to be a measure of cardiac sympathetic tone. Objectives: No ethnic-comparative data regarding BP, electrical or cardiac stress marker reactivity are available in sub-Saharan African individuals. Therefore, the objectives were firstly, to indicate and compare ethnic-specific differences in BP, QTc and cardiac stress reactivity during acute mental stress application. Secondly, to signify that α-adrenergic BP responses will associate with increased QTc prolongation and cardiac stress levels in Africans. Thirdly, to illustrate that an α-adrenergic BP response, QTc and cardiac stress markers’ reactivity will indicate pre-clinical alterations in the loading conditions and structure of the heart. Methodology: This cross-sectional, comparative target population study forms part of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SAPBA) study. The SABPA study was conducted between late summer until autumn in both 2008 (Africans) and 2009 (Caucasians) so as to avoid seasonal variations. The Health Research Ethics Committee (HREC) of the North-West University Potchefstroom Campus approved this study and all voluntary participants gave written informed consent prior to their inclusion in the study. All procedures pertained to the applicable institutional guidelines as stated by the Declaration of Helsinki. Exclusion criteria entailed the use of α-, β-blocker and psychotropic substance users, vaccination or blood donation within three months prior to the investigation, tympanum temperatures >37.5˚C and pregnant or lactating women. Participants were additionally excluded if they presented any sign of atrial fibrillation (N=16), history of myocardial infarction (N=4), electrocardiographic left ventricular hypertrophy (ECG-LVH) (N=1) and ventricular ectopic episodes (computationally excluded). The final sub-study sample comprised 388 teachers of whom 193 were urban dwelling Africans and 195 Caucasians. 24 hour Ambulatory BP measurements (24H ABPM) were recorded with the Cardiotens CE120®. Actical® accelerometers were equipped to attain physical activity recordings. Participants were requested to go to bed at 22h00, fasting overnight. The mentioned apparatus were removed the following day, followed by anthropometric measurements and blood sampling by a registered nurse. Fasting glucose, whole blood glycated haemoglobin, total cholesterol, high-density lipoproteins (HDL), as well as lifestyle markers such as gamma glutamyl transferase (alcohol consumption) and cotinine (smoking) were determined. The Finapres continuously assessed beat-to-beat BP changes throughout psychophysiological testing. Resting beat-to-beat BP and 10-lead ECG measurements were obtained for 5 min, followed by venous blood sampling. After a period of 5-10 min, the Stroop colour-word-conflict test was administered for 1 min, during which beat-to-beat BP and ECG responses were obtained. Another blood sample was obtained 10 min post-stress application. These blood samples (both prior and post-stress) were analysed for cardiac stress markers, cTnT and NT-proBNP, via electrochemiluminescence. The normality of all variables was verified and descriptive t-tests depicted ethnic characteristics. Chi-square statistics determined proportions and prevalence. Two-way ANCOVAs determined the least square mean difference in reactivity markers between ethnic groups, independent of a priori covariates. Regression analyses were performed in three models and F to enter was set at 2.5. For all the aforementioned analyses, significance was set at a p≤0.05. Additionally, receiver-operated characteristics (ROC) analyses determined ethnic-specific cTnT cut-point values predicting 24 hour diastolic hypertension (24H DBP HT). Odds ratios (OR) were also calculated for several models to establish CVD risk relation to RaVL amplitude increases in the detectable cTnT category in each ethnicity respectively. Results: A higher risk of cardiovascular vulnerability was observed in Africans as well as an increased RaVL amplitude, ECG-LVH prevalence and greater average number of ischemic events. Resting values for cardiovascular markers were quite similar between ethnicities. However, the degree to which these values changed during acute mental stress testing differed significantly. Acute mental stress responses of Africans were accompanied by a typical α-adrenergic response profile, whereas Caucasians predominantly presented a central cardiac β-adrenergic response pattern. A positive association existed between cTnT and NT-proBNP reactivity, in both ethnic groups, yet it was greater in the Caucasian group. ROC analyses revealed a higher cTnT cut-point during acute mental stress predicting 24H DBP HT in Africans (4.19pg.mL) compared to that of Caucasians (3.24pg/mL). An increased RaVL amplitude was associated with increased levels of cTnT during acute stress, in both ethnicities, giving rise to an OR of approximately 11. Conclusion: Cardiac stress (cTnT and NT-proBNP) and QTc reactivity were independently associated with an increased pre-clinical risk of structural and mechanistic alterations, specifically in the SABPA African cohort. In this African group, where cardio-metabolic vulnerability and α-adrenergic reactivity are predominant, the aforementioned modifications may be detrimental, evidenced by an increased DBP HT, CVD, ischemia and CAD. Increased cardiac stress and QTc reactivity, associated with α-adrenergic reactivity, may contribute to early sensitization and damage to the myocardium as well as signs of CVD, especially in an at-risk population MSc (Physiology), North-West University, Potchefstroom Campus, 2017

2016-01-01T00:00:00Z Veiga, Reinaldo Silverio http://hdl.handle.net/10394/25115 2017-07-06T10:01:54Z 2017-01-01T00:00:00Z

A proposed green planning development framework : integration of spatial planning and green infrastructure planning approaches Veiga, Reinaldo Silverio Throughout human history, civilizations have impaired their own chances of survival by damaging their own environment as they did not follow sustainable practises (Diamond, 2005). For over 40 years humankind’s demand on nature has exceeded what the earth can replenish (World Wildlife Fund et al., 2014:10). Recent research suggests that humanity uses 40% more resources every year than what is placed back by nature, as trees are cut faster than they mature, more fish are harvested than what oceans replenish and more carbon is emitted into the atmosphere faster than forests and oceans can absorb (Lorek and Fuchs, 2011:2). The earth’s finite resources, along with the provision of ecosystem services that are linked to the well-being of humanity and human settlements (Cilliers et al., 2013: 1; TEEB, 2011:1) are now considered an integral part of spatial planning approaches. The challenge, however, lies in successfully integrating and aligning green infrastructure planning as part of mainstream spatial planning approaches. This research presented a point of departure for such integration by creating and proposing a Green Planning Development Framework to guide the integration of spatial planning and green infrastructure planning. Such framework was based on (1) a literature study encompassing research on sustainability and sustainable development; green infrastructure planning; relevant international and national policies and legislation, and current frameworks and performance indices; (2) an empirical investigation and comparative analysis of international and local case studies based on identified best-practice approaches, along with (3) a local case study illustrating the proposed Green Planning Development Framework’s application and added value. Based on the theoretical grounding, empirical investigations and application of the proposed framework, specific conclusions and recommendations were made to guide future Green Planning Development from a spatial perspective MArt et Scien ((Urban and Regional Planning), North-West University, Potchefstroom Campus, 2017

2017-01-01T00:00:00Z Van Zyl, Susara Susanna http://hdl.handle.net/10394/25114 2017-07-06T10:01:28Z 2016-01-01T00:00:00Z

Promoting oral proficiency through art-making in grade R Van Zyl, Susara Susanna The ability to communicate (including speaking and listening) is an essential life skill for all learners, as it underpins a learner’s social, emotional and intellectual development. However, Grade R learners may not always be able to effectively understand and/or speak the language used at school for classroom instruction. This language used for classroom instruction is called the Language of Learning and Teaching (LoLT), and is of crucial importance to a learner’s success in many areas. The LoLT involves more than the ability to communicate in everyday conversational contexts, but is specifically related to the use of language for academic purposes. In South Africa, monolingualism is the exception rather than the norm (Olivier, Anthonissen, & Southwood, 2010). This poses several challenges to parents and teachers in selecting and using a LoLT in educational programmes (Olivier et al., 2010; South Africa, 2003). Even though mother-tongue education is seen as an educationally sound policy, the majority of South Africans prefer English and not their home language as LoLT (South Africa, 2003). A result of this choice is that many English Second Language (ESL) learners experience barriers to learning because of limited English proficiency. This may significantly delay or sometimes even permanently impede learners’ academic development (De Witt, Lessing, & Dicker, 1998). It is therefore important that learners can function in the LoLT if they are to master the skills necessary to proceed to the next level or Grade. When taking the above into consideration, a Grade R language programme which intends to incorporate oral proficiency, and specifically vocabulary enrichment, is essential. Meaningful vocabulary instruction should be facilitated, especially for learners from families where English proficiency is an issue (Hay & Fielding-Barnsley, 2007; Marvin & Wright, 1997; Schiff-Myers, Djukic, McGovern-Lawler, & Peres, 1993). The informal nature of the Grade R classroom assists in the promotion of oral proficiency and especially vocabulary enrichment through various learning activities. These learning activities include art-making, which may promote acquisition of vocabulary. During these activities, learners may be encouraged to express themselves and to communicate freely. The process of art-making itself helps to develop cognitive skills that aid in symbolic thinking (Camnizer, 2009; Read, 2008; Shumaker, 2009). Taking the above into consideration, it may be said that when young learners take part in art-marking activities, various senses are involved, as is the case with language activities. Participating in art-based lesson plans that incorporate language skills may appeal to various senses and learning styles, with the added possibility of enhancing oral proficiency (Read, 2008). In this study, various ways in which art-making can be utilised to promote oral proficiency, with specific reference to vocabulary enrichment, were investigated MEd (Learner Support), North-West University, Potchefstroom Campus, 2017

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