Acne vulgaris is the single, most common disease that presents a significant challenge to dermatologists, due to its complexity, prevalence and range of clinical expressions. This condition can be found in 85% of teenage boys and 80% of girls (Gollnick, 2003:1580). Acne can cause serious psychological consequences (low self–esteem, social inhibition, depression, etc.), if left untreated, and should therefore be recognised as a serious disorder (Webster, 2001:15). The pathogenesis of acne is varied, with factors that include plugging of the follicle, accumulation of sebum, growth of Propionibacterium acnes (P. acnes), and inflammatory tissue responses (Wyatt et al., 2001:1809). Acne treatment focuses on the reduction of inflammatory and non–inflammatory acne lesions, and thus halts the scarring process (Railan & Alster, 2008:285). Non–inflammatory acne lesions can be expressed as open and closed comedones, whereas inflammatory lesions comprise of papules, pustules, nodules and cysts (Gollnick, 2003:1581). Acne treatment may be topical, or oral. Topical treatment is the most suitable first–line therapy for non–inflammatory comedones, or mildly inflammatory disease states, with the advantage of avoiding the possible systemic effects of oral medications (Federman & Kirsner, 2000:80). Topical retinoids were very successfully used for the treatment of acne in the 1980s. Their effectiveness in long–term therapies was limited though, due to local skin irritations that occurred in some individuals (Julie & Harper, 2004:S36). Vitamin A acetate presented a new approach in the treatment of acne, showing less side effects (Cheng & Depetris, 1998:7). In this study, vitamin A acetate and zinc acetate were formulated into semisolid, combination formulations for the possible treatment of acne. Whilst vitamin A controls the development of microcomedones, reduces existing comedones, diminishes sebum production and moderately reduces inflammation (Verschoore et al., 1993:107), zinc normalises hormone imbalances (Nutritional–supplements–health–guide.com, 2005:2) and normalises the secretion of sebum (Hostýnek & Maibach, 2002:35). Although the skin presents many advantages to the delivery of drugs, it unfortunately has some limitations. The biggest challenge in the transdermal delivery of drugs is to overcome the natural skin barrier. Its physicochemical properties are a good indication(s) of the transdermal behaviour of a drug. The ideal drug to be used in transdermal delivery would have sufficient lipophilic properties to partition into the stratum corneum, but it would also have sufficient hydrophilic properties to partition into the underlying layers of the skin (Kalia & Guy, 2001:159). Pheroid technology was also implemented during this study, in order to establish whether it would enhance penetration of the active ingredients across the skin. The Pheroid consists of vesicular structures that contain no phospholipids, nor cholesterol, but consists of the same essential fatty acids that are present in humans (Grobler et al., 2008:283). The aim of this study hence was to investigate the transdermal delivery of vitamin A acetate and zinc acetate, jointly formulated into four topical formulations for acne treatment. Vitamin A acetate (0.5%) and zinc acetate (1.2%) were formulated into a cream, Pheroid cream, emulgel and Pheroid emulgel. An existing commercial product, containing vitamin A acetate, was used to compare the results of the formulated products with. The transdermal, epidermal and dermal diffusion of the formulations were determined during a 6 h diffusion study, using Franz diffusion cells and tape stripping techniques. Experimental determination of the diffusion studies proved that vitamin A acetate did not penetrate through the skin. These results applied to both the formulations being developed during this study, as well as to the commercial product. Tape stripping studies were done to determine the concentration of drug present in the epidermis and dermis. The highest epidermal concentration of vitamin A acetate was obtained with the Pheroid emulgel (0.0045 ug/ml), whilst the emulgel formulation provided the highest vitamin A acetate concentration in the dermis (0.0029 ug/ml). Contrary, for the commercial product, the total concentration of vitamin A acetate in the epidermis was noticeably lower than for all the new formulations studied. Vitamin A acetate concentrations of the commercial product in the dermis were within the same concentration range as the newly developed formulations, with the exception of the emulgel that delivered approximately 31% more vitamin A acetate to the dermis, than the commercial product. Zinc acetate was able to diffuse through full thickness skin, although no flux values were obtained. To eliminate the possibility of endogenous zinc diffusion, placebo formulations (without zinc) were prepared for use as control samples during the skin diffusion investigation. The emulgel and Pheroid emulgel formulations were unable to deliver significant zinc acetate concentrations transdermally, although transdermal diffusion was attained from both the cream and Pheroid cream. Tape stripping experiments with placebo formulations relative to the formulated products revealed that zinc acetate concentrations in the epidermis and dermis were significantly higher when the placebo formulations were applied. However, the average zinc acetate concentration in the dermis, after application of the cream formulation, was significantly higher, compared to when the placebo cream was applied. It could therefore be concluded that no zinc acetate had diffused into the epidermis and dermis from the new formulations, except from the cream formulation. The zinc acetate concentration being measured in the epidermis thus rather represented the endogenous zinc acetate. The cream formulation, however, was probably able to deliver detectable zinc acetate concentrations to the epidermis. Stability of the formulated products was tested under a variety of environmental conditions to determine whether the functional qualities would remain within acceptable limits over a certain period of time. The formulated products were tested for a period of three months under storage conditions of 25°C/60% RH (relative humidity), 30°C/60% RH and 40°C/75% RH. Stability studies included stability indicating assay testing, the determination of rheology, pH, droplet size, zeta–potential, mass loss, morphology of the particles and physical assessment. The formulations were unstable over the three months stability test period. A change in viscosity, colour and concentration of the active ingredients were observed. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Non–melanoma skin cancer (NMSC) is the most common human malignancy and it is estimated that over 1.3 million cases are diagnosed each year in the United States (Neville et al., 2007:462). There are three main types of NMSC, which include basal–cell carcinoma (BCC), squamous–cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). Exposure to ultra–violet (UV) radiation plays a major role in the aetiology of these three skin cancer types (Franceschi et al., 1996:24). 5–Fluorouracil is an antineoplastic pyrimidine analogue that functions as an anti–metabolite. It interferes with DNA (deoxyribonucleic acid), and to a lesser extent, with RNA (ribonucleic acid) synthesis by blocking the methylation of deoxyuridylic acid into thymidylic acid. It is used in topical preparations for the treatment of actinic keratosis (AK) and NMSC. The cure rate with topical 5–fluorouracil is partly reflected by the degree of erythema, erosions, and eventual crusting which develop at the sites of treatment. This reaction often attains the best clinical response, but in turn, frustrates patients, which may lead to patient incompliance (McGillis & Fein, 2004:175). Due to the hydrophilic nature of 5–fluorouracil, the transdermal permeation through the lipophilic stratum corneum is very low and trivial (Singh et al., 2005:99). Transdermal drug delivery is the delivery of a chemical substance across the skin to reach the systemic circulation (Prausnitz et al., 2004:115). This unique drug transport mechanism suggests many advantages that include safety, patient compliance, user–friendliness, efficiency and non–invasiveness (Fang et al., 2004:241). The stratum corneum is a specialised structure that forms part of several anatomically distinct layers of the skin. Seeing that it is the outermost layer, it provides protection to the skin. It is known as the main barrier to percutaneous absorption of compounds, as well as water loss, through the skin (Bouwstra et al., 2003:4). This study focussed on the formulation of six different types of semisolid formulations, containing 0.5% 5–fluorouracil. The formulations included: a cream, Pheroid cream, emulgel, Pheroid emulgel, lotion and Pheroid lotion. Pheroid refers to a delivery system which was incorporated in the formulations in an attempt to enhance the penetration of 5–fluorouracil into the skin. This drug delivery system consists of unique and stable lipid–based submicronand micron–sized structures, formulated in an emulsion. The dispersed Pheroid structures largely comprise of natural essential fatty acids, which have an affinity for the cell membranes of the human body (Grobler et al., 2008:284–285). These formulations were manufactured in large quantities and stored at three different temperatures, each with their respective relative humidity (RH): 25 °C/60% RH, 30 °C/60% RH and 40 °C/70% RH, for a period of six months. Stability tests were conducted on each of these formulations on the day of manufacture (month 0), and then after 1, 2, 3 and 6 months. The tests included: determination of concentration of the analytes (assay) by means of high performance liquid chromatography (HPLC); determination of zeta–potential and droplet size; pH measurement; viscosity; mass loss determination; physical appearance; and particle size distribution. Franz cell skin diffusion tests were performed with these six 5–fluorouracil containing semisolid formulations (0.5%), as well as with a 0.5% Pheroid solution, 0.5% non–Pheroid solution. A 5.0% Pheroid solution and a 5.0% non–Pheroid solution were also prepared in order to compare the skin diffusion test results to a 5.0% commercially available ointment. The data of the 0.5% formulations and solutions, as well as the 5.0% solutions and commercial ointment, were statistically compared and those formulations (and solutions) that yielded the best results, with regard to % diffused, epidermis and dermis concentrations, were identified. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

This report is a hermeneutic analytical study of a practical pedagogical situation. For three occasions I observed my own practice as a dance teacher and how a moment, choreographic approach in the governing documents for upper secondary school GY11 was executed in a group of dance students. The part is formulated in the course objectives for the courses on the arts program under the topic Dansgestaltning with focus on choreographic approach. The study is based on a socio-cultural thinking but also takes into account the prevailing gender theories and focuses on how the process of formulation level, through the transformation level is portrayed in the realization level of the dance regarding choreographic approach. The study illustrates educational research from both a dance perspective and a school development perspective. The intention of this study was to raise the awareness of how a pedagogical situation was designed and what is realized in the dance studio. Some pedagogical models are described as useful in raising awareness of the process and the realization of the aspect of moment in a dance studio. The methodology used for the study was participant observation and focus conversations. The results are reported in a discussion on a larger awareness of my own practice, and the benefits it can bring to learning, dancing and school development.

A stiffened DKT shell element is formulated for the linear static analysis of stiffened plates and shells. Three-noded triangular shell elements and two-noded beam elements with 18 and 12 degrees of freedom are used respectively in the formulation. The stiffeners follow the nodal lines of the shell element. Eccentricity of the stiffener is taken into account. The dynamic and stability characteristic of the element is also investigated. With the developed computer program, the results obtained by the proposed element agrees fairly well with the existing literature.

The U.S. disability population is growing at significant rates among adults as well as youth. According to the 2000 Current Population Reports, approximately 54 million Americans about 1 in 5 - are affected by the presence of a disability stemming from birth or life incident. Demographic increases are also noted among American youth as well, with one in 166 children is diagnosed with autism - estimated 67 children each day. Consequently, there have been federal-level responses in the form of legislation, executive orders and local-level program flinding such as REMS grants - addressing various disability issues. Likewise in recent years, another critically important matter has emerged with increasing priority on the nation s policy agenda: school emergency preparedness planning. A broad spectrum of crises incidents, ranging from student-initiated assaults to natural or man-made disasters, has become a well-documented reality where schools have experienced tragic impacts sometimes as severe as mass casualties These occurrences, coupled with an expected increase in potential evacuees with special needs, demonstrate the critical need for inclusive school evacuation planning at all levels of administration that actively considers its impact on vulnerable populations. This is of particular importance to public schools today; the presence of disabled students can be deduced from U.S. Census and NOES statistics while studies conducted by Georgia Tech s Center for Assistive Technology and Environmental Access (CATEA) illustrate the presence of teachers with disabilities. As the scope of interest in this field expands, the availability of related literature becomes more prevalent as well. While disability preparedness planning in schools is briefly mentioned in some articles and reports on emergency preparedness in general, it has yet to be the sole focus of one to date. Policymakers and practitioners in preparedness planning would likely benefit by broadening to its literature scope to include research that focuses solely on analyzing policy strategies and processes used in school emergency preparedness planning for students and teachers with disabilities. Therefore, this thesis project will compile available related literature into a topology in aimotated bibliography form through the lens of disability preparedness planning and policy in public schools. The research goal is to provide a qualitative assessment of available literature in the form of a reference guide of strategies and recommendations on disability preparedness, specifically intended for public school settings. Additionally, this compilation will outline the rationale supporting a more inclusive policy and planning formulation processes that actively engage the needs students and teachers with disabilities prior to the implementation stage.

No description available.

The applications of dense gas technology (DGT) in modern particle engineering have shown promising results in producing submicron particles with uniform particle morphology. In this study, two configurations of dense gas antisolvent processes were employed for the micronization, encapsulation and co-precipitation of pharmaceutical compounds. The encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs) by a pH-responsive polymer (Eudragit?? S100) was successfully performed using the supercritical antisolvent (SAS) process. Nanocomposites of less than 200nm in diameter with encapsulated SPIONs content as high as 16 wt% were achieved. Magnetic characterization of the product was also performed and the data were fitted by the Langevin equation. The superparamagnetic properties of the composites were preserved and the effective magnetic size was about 10 nm. The magnetically and pH-responsive nanocomposites can be potentially utilized as magnetic resonance imaging contrast agents and drug carriers. Screening experiments of 8 active pharmaceutical ingredients and 5 pharmaceutical excipients were performed using the recently patented atomized rapid injection solvent extraction (ARISE) process. Candidates with promising product morphology and recovery were selected for co-precipitation studies. The co-precipitation of the anti-cancer drug 5-fluorouracil (5FU) and poly l-lactic acid (PLLA) was conducted to develop a controlled release system. Experiments were designed based on a two-level, three-factor factorial design, in order to investigate the effects of processing parameters on product characteristics. Submicron PLLA-5FU composites (diameter<0.8 ??m) with a drug loading of 7.4 wt% were produced.

Abstract Peptide surfactants developed in the Centre for Biomolecular Engineering at The University of Queensland are engineered to combine the advantages of traditional surfactants with biodegradability, biocompatibility, formation of a mechanically strong interfacial cohesive network, and reversible stimuli-responsiveness. In this project, the potential of peptide-stabilised emulsions as delivery systems for small interfering RNA (siRNA) was explored. In recent years, the potential of siRNA as a new class of therapeutics has attracted great attention. The ubiquitous nature of RNA interference (RNAi) implies that siRNA can be used to silence any disease-causing gene to treat any disease. The hurdle that needs to be overcome to turn siRNA therapy into clinical reality is its delivery into the cytosol, where gene silencing by siRNA occurs. Although numerous systems have been developed for the delivery of siRNA, safety and efficiency are major concerns associated with current formulations. Therefore this project aimed to prepare a stable peptide emulsion formulation and to conduct initial tests of its ability to deliver siRNA in vitro. The human tumour suppressor gene p53 and the human breast cancer MCF-7 cell line were used as the model gene and model cell line, respectively. The commercially available lipid-based transfection reagent Lipofectamine™ 2000 was used as the benchmark control. Sonication and membrane extrusion were used to formulate emulsions with droplet size (d=120 nm) suitable for intravenous applications using peptide surfactant in the presence of Zn(II). Although these peptide emulsions are stable by themselves and in bovine serum, emulsion stability was found to be strongly affected by the presence of salt, EDTA, and proteins. The instability of AM1 emulsion in cell culture media has been a concern when it was subjected to in vitro cell culture tests. AM1-stabilised emulsion droplets were shown to be taken up by MCF-7 cells. However, siRNA when coupled with AM1 emulsion was not delivered into cells. Cytotoxicity studies showed that peptide surfactants did not exhibit high-level toxicity to CHO cells at the tested concentrations (0.25-2 mg mL-1). AM1 peptide-stabilised emulsions were mildly toxic to CHO cells but no toxicity was observed with MCF-7 cells. Future work could include evaluation of peptide emulsion-siRNA complex formation, and exploring the effects of different cell culture media compositions on emulsion stability and their relation to cytotoxicity.

Contextual information retrieval (CIR) is a critical technique for today’s search engines in terms of facilitating queries and returning relevant information. Despite its importance, little progress has been made in its application, due to the difficulty of capturing and representing contextual information about users. This thesis details the development and evaluation of the contextual SERL search, designed to tackle some of the challenges associated with CIR from the World Wide Web. The contextual SERL search utilises a rich contextual model that exploits implicit and explicit data to modify queries to more accurately reflect the user’s interests as well as to continually build the user’s contextual profile and a shared contextual knowledge base. These profiles are used to filter results from a standard search engine to improve the relevance of the pages displayed to the user. The contextual SERL search has been tested in an observational study that has captured both qualitative and quantitative data about the ability of the framework to improve the user’s web search experience. A total of 30 subjects, with different levels of search experience, participated in the observational study experiment. The results demonstrate that when the contextual profile and the shared contextual knowledge base are used, the contextual SERL search improves search effectiveness, efficiency and subjective satisfaction. The effectiveness improves as subjects have actually entered fewer queries to reach the target information in comparison to the contemporary search engine. In the case of a particularly complex search task, the efficiency improves as subjects have browsed fewer hits, visited fewer URLs, made fewer clicks and have taken less time to reach the target information when compared to the contemporary search engine. Finally, subjects have expressed a higher degree of satisfaction on the quality of contextual support when using the shared contextual knowledge base in comparison to using their contextual profile. These results suggest that integration of a user’s contextual factors and information seeking behaviours are very important for successful development of the CIR framework. It is believed that this framework and other similar projects will help provide the basis for the next generation of contextual information retrieval from the Web.

PhD / Electrostatics of aerosols for inhalation is a relatively new research area. Charge properties of these particles are largely unknown but electrostatic forces have been proposed to potentially influence lung deposition. Investigation on the relationship between formulation and aerosol charging is required to understand the fundamental mechanisms. A modified electrical low pressure impactor was employed to measure the particles generated from metered dose inhalers and dry powder inhalers. This equipment provides detailed size and charge information of the aerosols. The particles were sized by impaction onto thirteen stages. The net charges in twelve of the size fractions were detected and recorded by sensitive electrometers. The drug deposits were quantified by chemical assay. The aerosol charge profiles of commercial metered dose inhalers were product-dependent, which was due to differences in the drug, formulation, and valve stem material. The calculated number of elementary charges per drug particle of size ≤ 6.06 μm ranged from zero to several ten thousands. The high charge levels on particles may have a potential effect on the deposition of the aerosol particles in the lung when inhaled. New plastic spacers marketed for use with metered dose inhalers were found to possess high surface charges on the internal walls, which was successfully removed by detergent-coating. Detergent-coated spacer had higher drug output than the new ones due to the reduced electrostatic particle deposition inside the spacer. Particles delivered from spacers carried lower inherent charges than those directly from metered dose inhalers. Those with higher charges might be susceptible to electrostatic forces inside the spacers and were thus retained. The electrostatic low pressure impactor was further modified to disperse two commercial Tubuhaler® products at 60 L/min. The DPIs showed drug-specific responses to particle charging at different RHs. The difference in hygroscopicity of the drugs may play a major role. A dual mechanistic charging model was proposed to explain the charging behaviours. The charge levels on drug particles delivered from these inhalers were sufficiently high to potentially affect deposition in the airways when inhaled. Drug-free metered dose inhalers containing HFA-134a and 227 produced highly variable charge profiles but on average the puffs were negatively charged, which was thought to be due to the electronegative fluorine atoms in the HFA molecules. The charges of both HFAs shifted towards neutrality or positive polarity with increasing water content. The spiked water might have increased the electrical conductivity and/or decreased the electronegativity of the bulk propellant solution. The number of elementary charges per droplet decreased with decreasing droplet size. This trend was probably due to the redistribution of charges amongst small droplets following electrostatic fission of a bigger droplet when the Raleigh limit was reached.