1834 research outputs found
Sort by
The effect of solid-state forms on the topical delivery of roxithromycin
No full textThe skin is a very accessible and convenient route of administration for topical and systemic drugs (Williams, 2003:1). The only problem most formulators face is overcoming the barrier function of the stratum corneum, which has proved to be quite a challenge (Varun et al., 2012:632). This being said, the topical/transdermal route still holds many advantages over other routes of administration, with the most obvious being no first-pass effect from the liver and being a non-invasive, painless route of administration (Washington et al., 2001:187). The skin itself is affected by many diseases and one of the most common, from which a large number of the population suffers, is acne (Bershad, 2001:279). Acne vulgaris is a chronic inflammatory disease which affects the pilosebaceous units found in the dermis layer of the skin and the micro-organism which accumulates in these sebaceous glands and causes the inflammation, is known as Propionibacterium acnes. Topical antibiotics have a direct affect against P. acnes found in the sebum glands and in this way reduce the acne inflammation (Williams et al., 2012:361, 364). The antibiotics used today for the treatment of acne have been reported to be up to 60% resistant to the acne causing bacteria (P. acnes) (Scheinfeld et al., 2003:43). In the recent past, trials have been conducted on newer antibiotics for acne treatment, one in particular is roxithromycin (Oschsendorf, 2006:830).
Roxithromycin is a macrolide antibiotic which has a bacteriostatic effect on P. acnes which accumulates in the dermis, but its poor solubility has been a major drawback for topical drug formulation (Gollnick, 2003:1585; Medsafe, 2014). For optimal skin penetration, a compound must preferably have an aqueous solubility above 1 mg/ml (Williams, 2003:37) and roxithromycin was reported to have a solubility of only 0.0335 mg/ml at 25 °C, which is below the optimal solubility for topical penetration (Aucamp et al., 2013:26; Williams, 2003:37). It has previously been proved that by using amorphous forms of a compound, along with its changed crystal lattice, can result in improved drug properties including increased solubility (Biradar et al., 2006:22; Purohit & Venugopalan, 2009:883). Patents from Liebenberg et al. (2013) and Liebenberg & Aucamp (2013) proved the glassy amorphous form of roxithromycin and the chloroform desolvated amorphous form had improved solubilities in comparison to the crystalline monohydrate form.
Another area of research that has shown much growth is that of vesicle carrier systems, which have the ability to improve therapeutic activity of drugs by increasing the topical delivery of especially poorly soluble drugs such as roxithromycin (Bansal et al., 2012:704). Niosomes are used as an alternative to liposomes in current years as it overcomes the chemical instability, high cost and lack of purity of phospholipids (Jadon et al., 2009:1186). Niosomes are liposomes which are prepared using non-ionic surfactants instead of phospholipids and ufosomes are liposomes made from fatty acids (Bansal et al., 2012:710; Williams, 2003:128-129). Provesicular systems, such as proniosomes and pro-ufosomes, are prepared in order to overcome the stability problems that vesicular carriers face (Bansal et al., 2012:706, 709).
The aim of this study was to determine if the two amorphous forms of roxithromycin, namely the glassy form and the chloroform desolvate, coupled with better solubility would have better topical diffusion. These three solid-state forms were each encapsulated into four chosen vesicle systems namely, niosomes, proniosomes, ufosomes and pro-ufosomes and the delivery of the two amorphous forms were compared to that of the crystalline monohydrate form to determine if an increase in topical delivery took place. The target area for the active pharmaceutical ingredient (API) was the dermis, as this is the area where P. acnes accumulates (Gollnick, 2003:1585).
The optimisation and characterisation of amorphous forms entrapped in vesicles proved that all carrier systems were well formed and had optimal properties for topical delivery. An accurate and reliable high performance liquid chromatography (HPLC) method of analysis was developed and validated for the analysis of roxithromycin samples during experiments. The release studies showed that the API was successfully released from all carrier systems, with niosomes and proniosomes having superior release over the ufosomes and pro-ufosomes. The reason for this was that the API had higher affinity (and therefore less release) for the ingredients used to make ufosomes and pro-ufosomes (Agarwal et al., 2001:49; Dayan, 2005:74).
The topical diffusion studies showed that there was no API concentration detected in the stratum corneum, which meant the API successfully penetrated the barrier. There was practically no API found in the receptor phase of the Franz cells which indicated that there was no systemic absorption and that the vesicle systems aided in drug targeting. An API concentration was found in the epidermis-dermis of all vesicle systems, which proved the intended target area for roxithromycin was successfully reached. The vesicle systems which assisted in the delivery of roxithromycin and its amorphous forms, from highest to lowest diffused concentration, were niosomes, ufosomes, proniosomes and pro-ufosomes. The total concentration was more dependent on the carrier type than the solid-state form, as there was no obvious leading roxithromycin form. Nevertheless, when the solid-state forms were grouped together, regardless of what carrier systems they were delivered in, the amorphous forms had higher epidermis-dermis concentrations than the roxithromycin monohydrate. This suggests the amorphous forms retained their increased solubilities while entrapped and resulted in improved topical delivery.National Research Foundatio
Urban governance and spatial planning for sustainable urban development in Tamale, Ghana
No full textThis study investigated urban governance and spatial planning practices for sustainable urban development in Tamale, Ghana, regarding provision and access to urban infrastructure and basic services. This broad aim of the study was divided into three objectives, namely to 1) review of the statutory provisions for the conduct of urban governance and spatial planning in Ghana and Tamale, 2) assess the spatio-temporal growth dynamics and provision of urban infrastructure and basic services in Tamale, and 3) to explore stakeholder engagement in spatial planning in the city. Research questions that guided the study were: a) what is the extent of the physical expansion of Tamale and how does urban governance respond to the growth dynamics regarding infrastructure and service provision?, b) to what extent does the spatial growth patterns of the city reflect local and national development aspirations, c) what national and local statutory frameworks guide the practice of urban governance and spatial planning, d) what are the modes of stakeholder engagement in urban governance and spatial planning and who are the stakeholders, and e) is the city’s urban governance inclusive and amenable to decentralisation, entrepreneurialism and democratisation (DED) principles? The DED analytical framework and collaborative planning theoretical perspective were adopted to analyse urban governance practices and outcomes in Tamale. Four evaluative questions were addressed using the DED and collaborative planning frameworks, namely how urban governance is lived in Tamale, whether urban governance leads to job creation, and for whom, whether urban governance results in improved urban services and whether urban governance empowers people at the grass roots and promotes accountable governance.
A mixed methods research design was employed in the study. This comprised of quantitative analysis of the city’s spatial growth using remote sensing and geographic information systems techniques, and qualitative investigation of urban governance processes and outcomes. The results show that the legislative provisions guiding urban governance in Ghana have not been effective in promoting sustainable urban development leading to the country transitioning towards spatial development frameworks (SDFs) as alternative approaches. Also, both the city’s spatial and demographic growth has been phenomenal, but access to urban infrastructure and services has lagged behind. Moreover, there was limited stakeholder engagement in urban governance and that resulted in low accountability. In terms of the DED and collaborative planning frameworks, there were generally no straightforward answers to the evaluative questions, except with respect to the question of accountability, which was almost non-existent in the urban governance practices of Tamale. The study concludes by lauding efforts to reform urban governance laws and initiatives to engender participatory and partnership-based urban governance and service delivery in the city. It is recommended that these reforms should be encouraged and operationalised within real decentralisation, entrepreneurialism and democratisation. Comprehensive needs assessment, institutional and stakeholder capacity-building efforts, and empathic stakeholder engagements will be crucial in this regard, especially if social justice, economic viability, and environmental health and sustainability are considered in the management of the city’s urban growth. Further research is recommended to provide detailed understanding of urban governance outcomes in Tamale, such as the magnitude of job creation, distribution and sustainability.National Research Foundatio
Physiological coherence during live music performance a real time exploratory investigation using wireless systems
No full textFlow has been described in psychological literature as a state of energized focus where an individual becomes so engrossed in their doings that they experience an almost effortless, spontaneous and intuitive, yet highly focused state of optimal and autotelic experience. However neurophysiological research on flow is severely underdeveloped, while real-time research on flow within the context of musical creativity is surprisingly scarce considering how often optimal performance is reported in this context. An exploratory investigation was launched in order to assess the physiological underpinning of such flow experiences in the larger context of musical improvisation through the study of heart and brain wave activity in five professional jazz musicians. Using wireless electroencephalographic and electrocardiographic devices, subjects could improvise unhindered, and did so continuously while various brain and heart parameters were recorded in real-time. Through spectral analysis, power values for the different electroencephalographic frequency bands were quantified for the various stages of performance, and subsequently the shifts and trends in the data were described. Additionally, heart rate variability was calculated in order to assess the synergistic actions of the autonomic nervous system on the heart and the interplay between heart and brain during such high performance states of musical creativity. The research revealed the prominence of elevated theta activity persisting through performance and showed strong associations with subjective experiences of flow. Such high theta activity has been linked to high performance states in past and further evidence suggest the primary involvement of the right frontotemporal regions during improvisation. Furthermore, heart rate variability data suggested the growing presence of parasympathetic influence during such flow states, and together with the lower band dominance suggest trance-like behaviour and activation patterns within the brain. The study serves as basis for future research and the development of neurofeedback, music therapy and musical creativity protocols.National Research Foundatio
Communicating your research to a non-expert audience
No full textPresentations SA PhD Project Conference: KwaZulu-Natal Province 17 August 2016
SET policy – the Journey
No full textPresentations SA PhD Project Conference: Western Cape Province 13 September 2016.1. Introduction
2. SET Policy Evolution
3. The National System of Innovation
4. Key SET Policies (the White Paper on S&T; the NR&DS; the Ten Year Innovation Plan, the NDP, and the 9 Point Plan;
5. The System’s Performance
6. The new White Paper on S&T and the Decadal Pla
Publishing during your PhD
No full textPresentations SA PhD Project Conference: Gauteng Province 11 October 2016
Understanding your discipline: stem
No full textPresentations SA PhD Project Conference: Gauteng Province 11 October 2016.2
•Introduction
•Skills to acquire before embarking on a PhD
•Understanding your PhD requirements in your discipline
•Skills acquired during a PhD
•Personality traits
•Conclusio
Evaluation of extraction based fertilizer recommendations
No full textThere is a need to improve methods by which nitrogen, phosphorus and potassium are currently recommended. There is a considerable lack of mechanistical justifications for the methods used to recommend these nutrients. Lack of mechanistical justification can be attributed mainly to the disregard of nutrient (N, P and K) dynamics. Also the difficulty in incorporating these dynamics on fertilizer recommendation programs has compromised the mechanistical basis of extraction based approaches. The aim of the study was to evaluate these conventional (extraction based fertilizer recommendations) methods used to recommend these nutrients, by comparing their performance to the alternative approaches provided in this study. This evaluation was carried out through several studies, and a review of literature. From literature review it was apparent that there is indeed a need for revision of these methods. Their lack in mechanistical, technical and practical justification was considered and critically analyzed. It was proposed that alternative P and K recommendations can be achieved through quantity/intensity (Q/I) relations (amount of a respective nutrient in solution relative to the amount of nutrient adsorbed). It was also proposed that N recommendations can be improved by integrating mineralizable N. It was also concluded that these alternative approaches can routinely in a cost effective manner be determined.
The first chapter evaluated P and K Q/I relations in several South African soils. Parameters of K dynamics were derived from activity ratio diagrams and these were used to explain K dynamics. Phosphorus sorption curves were linearized by Langmuir equation, and parameters derived therefrom were used to evaluate P dynamics. It was found that pH measured in water had a correlation coefficient (R2) of 0.71 with P sorption maxima. It was also found that electrical conductivity could account for 76% variance in K intensity parameter. It was suggested that these correlations could be exploited further to empirically model these crucial parameters. Thus, these correlations provide a possibility of determining these parameters routinely.
Pot trials were also conducted to evaluate the crop response, when P or K was made with the alternative approaches using maize and potato as test crops. Conventional extraction approach recommended higher P rates, and the P uptake between the two methods was not significantly improved. The extraction based approach recommended lesser K rates and K uptake was significantly higher under the alternative approach. The impact of integrating mineralizable N on N recommendations was also evaluated under control conditions. It was found that although alternative N recommendation approach recommended lesser N rates the N uptake was not significantly reduced. In fact the non-significant trend was that N uptake was higher when N recommendations were made with an alternative approach. From these initial pot trials only one nutrient was allowed to vary and the rest were kept constant at optimum levels. The second set of pot trials were carried out (parallel to the previous one), and on this set, all three nutrients were allowed to vary per experimental units. On these NPK was recommended with alternative approach and compared to the conventional approach. The results obtained were similar to those obtained when N, P or K were allowed to vary individually. It was also suggested that total carbon can be used to assess the validity of these approaches. This was based on the consistent inverse correlation that was obtained between total carbon and P or K.
Field trials were also conducted at Ukulinga research farm Pietermaritzburg and Wartburg, using maize and potato as test crops. The lack of concurrent response from nutrient uptake was also observed here similar to the observations already made in pot trials. These were characterized by conventional method recommending higher rates of N and N uptake not concurrent with the rates. It was also found that there was a poor correlation between applied fertilizer and extraction based intensity parameters, with R2 ranging between 0.005 – 0.011, compared to R2 of Q/I parameter which was 0.98 for both P and K. This poor correlation was evident between nutrient uptake and total biomass. Yield of both maize and potato at both sites was higher when recommendations were made by alternative approaches, and yield grade of potatoes was also improved when the recommendations were made by alternative approach. Total biomass of maize was also significantly improved when the recommendations were made by the alternative approach. Earlier,
observation with regards to correlation of total carbon and nutrients was also observed under field conditions. This suggested that this is an important parameter to evaluate fertilizer recommendation program. It was concluded that recommending P and K with Q/I relations, and integrating mineralizable N on N recommendations is more mechanistically, technically, theoretically and practically justified compared to the conventional method.National Research Foundatio
The foundations of linguistics: mathematics, models, and structures
No full textThe philosophy of linguistics is a rich philosophical domain which encompasses various disciplines. One of the aims of this thesis is to unite theoretical linguistics, the philosophy of language, the philosophy of science (particularly mathematics and modelling) and the ontology of language. Each part of the research presented here targets separate but related goals with the unified aim of bringing greater clarity to the foundations of linguistics from a philosophical perspective.
Part I is devoted to the methodology of linguistics in terms of scientific modelling. I argue against both the Conceptualist and Platonist (as well as Pluralist) interpretations of linguistic theory by means of three grades of mathematical involvement for linguistic grammars. Part II explores the specific models of syntactic and semantics by an analogy with the harder sciences. In Part III, I develop a novel account of linguistic ontology and in the process comment on the type-token distinction, the role and connection with mathematics and the nature of linguistic objects.
In this research, I offer a structural realist interpretation of linguistic methodology with a nuanced structuralist picture for its ontology. This proposal is informed by historical and current work in theoretical linguistics as well as philosophical views on ontology, scientific modelling and mathematics.National Research FoundationNational Research Foundation (South Africa). Doctoral Abroad ScholarshipSt Leonard's Tuition waiverSt Andrews and Stirling PhD scholarshi