An energy, water and disease disaster management module: a technoeconomic feasibility analysis
- Authors: Nicholson, Thomas J
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/65167 , vital:28700
- Description: Intermittent energy and water supply are current challenges faced by many residents in South Africa. South Africa is one of the more water scarce countries in the world; this coupled with the lack of infrastructure makes it challenging to provide every citizen with their right to basic water and sanitation. With millennium development goal 7C not being addressed in many areas, residents experience sub-standard living conditions, which drastically increases the vulnerability of marginalised groups to epidemics. In the sustainable development goals improving sanitation and drinking water has been identified as one of the most effective and least expensive means of reducing fatalities and increasing public health. There is a need for a mobile laboratory that demonstrates power and water self-sufficiency, which is capable of on-site diagnosis and water treatment. The unit will have the ability to perform independent compliance monitoring of municipal water supply, treat inadequate water and provide surplus electricity to surrounding areas. A literature-based study was performed utilizing several scientific databases to identify current methods of power and water production in previous disaster management and humanitarian relief situations. Based on findings three example laboratories were theoretically designed; structural modelling, systems simulation and optimization and sensitivity analyses were performed with HOMER Pro, PackVol and SketchUp. A cost benefit analysis was performed with the social return on investment methodology. Novel human waste processing was performed with fly ash and simulated faeces. Bacterial species identification in ice samples was performed with the API 20E protocol and limited equipment as a proof of concept for field deployment. A hybrid system consisting of PV panels, a wind turbine and biomass generator showed promise for displaced humanitarian relief camps; with every 1 ZAR capital invested resulting in 3.13 ZAR social benefit. A system consisting of PV panels and a battery bank proved to have the least environmental impact and the grid supply laboratory showed a cheaper cost of energy alternative for needs provision. Fly ash showed potential as in nutrient recovery and as a fertility aid to soil. The units developed function as a means to increase disaster preparedness and humanitarian relief as well a means to improve quality of life for rural marginalize populations.
- Full Text:
- Date Issued: 2017
- Authors: Nicholson, Thomas J
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/65167 , vital:28700
- Description: Intermittent energy and water supply are current challenges faced by many residents in South Africa. South Africa is one of the more water scarce countries in the world; this coupled with the lack of infrastructure makes it challenging to provide every citizen with their right to basic water and sanitation. With millennium development goal 7C not being addressed in many areas, residents experience sub-standard living conditions, which drastically increases the vulnerability of marginalised groups to epidemics. In the sustainable development goals improving sanitation and drinking water has been identified as one of the most effective and least expensive means of reducing fatalities and increasing public health. There is a need for a mobile laboratory that demonstrates power and water self-sufficiency, which is capable of on-site diagnosis and water treatment. The unit will have the ability to perform independent compliance monitoring of municipal water supply, treat inadequate water and provide surplus electricity to surrounding areas. A literature-based study was performed utilizing several scientific databases to identify current methods of power and water production in previous disaster management and humanitarian relief situations. Based on findings three example laboratories were theoretically designed; structural modelling, systems simulation and optimization and sensitivity analyses were performed with HOMER Pro, PackVol and SketchUp. A cost benefit analysis was performed with the social return on investment methodology. Novel human waste processing was performed with fly ash and simulated faeces. Bacterial species identification in ice samples was performed with the API 20E protocol and limited equipment as a proof of concept for field deployment. A hybrid system consisting of PV panels, a wind turbine and biomass generator showed promise for displaced humanitarian relief camps; with every 1 ZAR capital invested resulting in 3.13 ZAR social benefit. A system consisting of PV panels and a battery bank proved to have the least environmental impact and the grid supply laboratory showed a cheaper cost of energy alternative for needs provision. Fly ash showed potential as in nutrient recovery and as a fertility aid to soil. The units developed function as a means to increase disaster preparedness and humanitarian relief as well a means to improve quality of life for rural marginalize populations.
- Full Text:
- Date Issued: 2017
Composition and fate of triclosan in the sludge from wastewater treatment in Grahamstown, South Africa and Tiaret, Algeria
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Development and assessment of gastric-retentive sustained release metronidazole microcapsules
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Development and assessment of ketoconazole intravaginal thermosetting hydrogel formulations
- Authors: Ramanah, Ashmita
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5198 , vital:20785
- Description: Imidazole compounds are commonly used as antifungal therapies and ketoconazole was the first broad spectrum orally active azole identified and registered. However, the risks of hepatotoxicity and drug interactions following systemic delivery and absorption of ketoconazole outweigh the therapeutic benefits and ketoconazole was therefore discontinued as first line systemic antifungal therapy in many countries. Although not yet banned in South Africa, the South African Medicine Formulary has ceased to recommend the use of ketoconazole for systemic treatment. Topical use of ketoconazole is, however, regarded as safe following extensive human use as low systemic absorption occurs following topical administration. Vulvo-vaginal candidiasis is a yeast infection that affects a large number of women, some of whom present with several infections annually. The topical treatment options for vulvo-vaginal candidiasis include the use of vaginal tablets, capsules, ovules and creams administered as a single dose or one to three times daily for three to fourteen days either alone or in combination with another dosage form depending on the regimen. Administration of the dose nightly is recommended for most vaginal creams and ovule formulation due to leakage and the uncomfortable feel of the dosage form if administered during the day. A thermosetting gel that remains in the vagina following administration and prolongs the release of ketoconazole from a once daily dose would be a useful addition to the arsenal for intra-vaginal antifungal therapy. Thermosetting gels would be more comfortable to administer as the gel would set in a form similar to naturally occurring mucous in the vagina and, if formulated with a low pH, irritation of the sensitive and fissured tissue would be minimised. A further benefit would be that once set the gel would loosely take on the anatomical shape of the vagina. A simple, precise, accurate, reproducible and sensitive stability-indicating reversed phase-high performance liquid chromatographic method using ultraviolet detection for the quantitation of ketoconazole was developed and validated. The method was specific and was applied to the determination of ketoconazole in commercial and experimental formulations in addition to samples from degradation studies and in vitro release testing. Product performance characteristics of commercial products were investigated with the goal to provide a strategy for the development of a novel intra vaginal gel in the shortest possible time. Characterisation of Xolegel®, Kez® shampoo and Ketazol® cream included an evaluation of pH, viscosity and assay, in addition to spectroscopic and thermal analysis, to identify ideal characteristics of topical products that could be used as targets during formulation development of the gel. An in vitro release method was developed and validated for precision and accuracy and the in vitro release profiles of commercial ketoconazole products were compared using analysis of variance, model dependent and independent approaches. Ketoconazole release data from test gel manufactured during formulation development were investigated to obtain information about the relationship between formulation content and drug release. Poloxamers marketed as Pluronic® and Lutrol® are synthetic non-ionic tri-block copolymers that consist of hydrophobic propylene oxide and hydrophilic polyethylene oxide blocks, which in solution interact to exhibit thermo-reversible behaviour. In situ forming hydrogels consisting of poloxamers, more specifically poloxamer 407, are activated following a temperature stimulus and undergo a sol to gel transition. This approach was used to produce a thermosetting vaginal gel that would exhibit a long residence time in the vagina with an associated enhancement of therapeutic efficacy. Ketoconazole- excipient compatibility was investigated during preformulation studies using spectroscopic and thermal analysis to enable the selection of excipients best suited for the production of a novel dosage form prior to formulation development activities. No obvious interactions between ketoconazole and excipient were observed and ketoconazole was found in an amorphous form when in combination with polysorbate 80 and poloxamers. A two-level factorial design was used to produce solvent systems with different amounts of polysorbate 80, citric acid and ethanol to identify a vehicle in which ketoconazole exhibited optimum solubility and at a pH that would be least irritating to the vaginal mucosa with a low content of excipients. The optimised vehicle consisted of 4% m/v citric acid, 1.5% v/v polysorbate 80 and 9.5% v/v ethanol made up to 50 g with citrate-phosphate buffer adjusted to pH 5.0, resulted in a vehicle of pH of 3.5 in which 71.41 mg of ketoconazole was dissolved per mL. A Central Composite Design was used to evaluate compositions for the modulation of viscosity of the thermosetting dosage form such that it was a liquid at 22 °C that rapidly formed a stiff gel when heated to 37 °C (intra-vaginal temperature) using different amounts of the poloxamer grades 407, 188 and 237. Thermosetting gels containing 2% m/v ketoconazole were manufactured using specifications generated using the Central Composite Design and the viscosity at 22 °C and 37 °C, solution to gel transition time, potency and ketoconazole release at 24, 48 and 72 hours investigated. Contour and three-dimensional response surface plots and mathematical relationships with target ranges set for responses were identified and with the aid of Central Composite Design the optimisation of a desirable thermosetting gel was achieved. The optimised composition included 16% m/v poloxamer 407, 10% m/v poloxamer 188 and 6% m/v poloxamer 237 in the gel that was used as the basis for further optimisation studies. The low ketoconazole release for ketoconazole observed indicated that the poloxamers had formed a gel matrix that sustained the release of ketoconazole and would therefore ensure that once daily administration of the gel was possible. The sol-gel transition test may be used as a simple and cheap alternative to viscosity testing for thermosetting formulations when expensive viscometers and rheometers are unavailable and was successfully used for this purpose.Ketoconazole is photolabile and is prone to degradation in aqueous solutions. The hydrophobic core of micelles formed in these dosage forms are believed to shield ketoconazole molecules and improve stability in aqueous solutions and acidic gels. The thermosetting gel optimised for poloxamer content was subjected to a further Central Composite Design in which sodium metabisulphite content and vehicle pH were investigated. The length of storage was used as a numeric variable and storage condition as a categoric variable at two levels to monitor the stability of the gels. The formulations were investigated at sample times of 0, 1, 2, 4 and 8 weeks at 5 °C, 25 °C and 40 °C. The use of a Central Composite Design facilitated an understanding of the interactions between input variables and their impact on the responses analysed including ketoconazole content, release at 24, 48 and 72 hours, gel pH and viscosity at 22 °C and 37 °C. Design of Experiments may be used as a rapid cost effective tool for an overall assessment of the stability of novel topical dosage forms. However, a more thorough assessment of stability may be required for product registration. Ketoconazole was found to be unstable in the acidic thermosetting gels despite the addition of antioxidant. The gels in liquid form at 5 °C and 25 °C have a low number of micelles for ketoconazole incorporation and therefore additional optimisation studies would be required to enhance the shelf-life of this product.
- Full Text:
- Date Issued: 2017
- Authors: Ramanah, Ashmita
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5198 , vital:20785
- Description: Imidazole compounds are commonly used as antifungal therapies and ketoconazole was the first broad spectrum orally active azole identified and registered. However, the risks of hepatotoxicity and drug interactions following systemic delivery and absorption of ketoconazole outweigh the therapeutic benefits and ketoconazole was therefore discontinued as first line systemic antifungal therapy in many countries. Although not yet banned in South Africa, the South African Medicine Formulary has ceased to recommend the use of ketoconazole for systemic treatment. Topical use of ketoconazole is, however, regarded as safe following extensive human use as low systemic absorption occurs following topical administration. Vulvo-vaginal candidiasis is a yeast infection that affects a large number of women, some of whom present with several infections annually. The topical treatment options for vulvo-vaginal candidiasis include the use of vaginal tablets, capsules, ovules and creams administered as a single dose or one to three times daily for three to fourteen days either alone or in combination with another dosage form depending on the regimen. Administration of the dose nightly is recommended for most vaginal creams and ovule formulation due to leakage and the uncomfortable feel of the dosage form if administered during the day. A thermosetting gel that remains in the vagina following administration and prolongs the release of ketoconazole from a once daily dose would be a useful addition to the arsenal for intra-vaginal antifungal therapy. Thermosetting gels would be more comfortable to administer as the gel would set in a form similar to naturally occurring mucous in the vagina and, if formulated with a low pH, irritation of the sensitive and fissured tissue would be minimised. A further benefit would be that once set the gel would loosely take on the anatomical shape of the vagina. A simple, precise, accurate, reproducible and sensitive stability-indicating reversed phase-high performance liquid chromatographic method using ultraviolet detection for the quantitation of ketoconazole was developed and validated. The method was specific and was applied to the determination of ketoconazole in commercial and experimental formulations in addition to samples from degradation studies and in vitro release testing. Product performance characteristics of commercial products were investigated with the goal to provide a strategy for the development of a novel intra vaginal gel in the shortest possible time. Characterisation of Xolegel®, Kez® shampoo and Ketazol® cream included an evaluation of pH, viscosity and assay, in addition to spectroscopic and thermal analysis, to identify ideal characteristics of topical products that could be used as targets during formulation development of the gel. An in vitro release method was developed and validated for precision and accuracy and the in vitro release profiles of commercial ketoconazole products were compared using analysis of variance, model dependent and independent approaches. Ketoconazole release data from test gel manufactured during formulation development were investigated to obtain information about the relationship between formulation content and drug release. Poloxamers marketed as Pluronic® and Lutrol® are synthetic non-ionic tri-block copolymers that consist of hydrophobic propylene oxide and hydrophilic polyethylene oxide blocks, which in solution interact to exhibit thermo-reversible behaviour. In situ forming hydrogels consisting of poloxamers, more specifically poloxamer 407, are activated following a temperature stimulus and undergo a sol to gel transition. This approach was used to produce a thermosetting vaginal gel that would exhibit a long residence time in the vagina with an associated enhancement of therapeutic efficacy. Ketoconazole- excipient compatibility was investigated during preformulation studies using spectroscopic and thermal analysis to enable the selection of excipients best suited for the production of a novel dosage form prior to formulation development activities. No obvious interactions between ketoconazole and excipient were observed and ketoconazole was found in an amorphous form when in combination with polysorbate 80 and poloxamers. A two-level factorial design was used to produce solvent systems with different amounts of polysorbate 80, citric acid and ethanol to identify a vehicle in which ketoconazole exhibited optimum solubility and at a pH that would be least irritating to the vaginal mucosa with a low content of excipients. The optimised vehicle consisted of 4% m/v citric acid, 1.5% v/v polysorbate 80 and 9.5% v/v ethanol made up to 50 g with citrate-phosphate buffer adjusted to pH 5.0, resulted in a vehicle of pH of 3.5 in which 71.41 mg of ketoconazole was dissolved per mL. A Central Composite Design was used to evaluate compositions for the modulation of viscosity of the thermosetting dosage form such that it was a liquid at 22 °C that rapidly formed a stiff gel when heated to 37 °C (intra-vaginal temperature) using different amounts of the poloxamer grades 407, 188 and 237. Thermosetting gels containing 2% m/v ketoconazole were manufactured using specifications generated using the Central Composite Design and the viscosity at 22 °C and 37 °C, solution to gel transition time, potency and ketoconazole release at 24, 48 and 72 hours investigated. Contour and three-dimensional response surface plots and mathematical relationships with target ranges set for responses were identified and with the aid of Central Composite Design the optimisation of a desirable thermosetting gel was achieved. The optimised composition included 16% m/v poloxamer 407, 10% m/v poloxamer 188 and 6% m/v poloxamer 237 in the gel that was used as the basis for further optimisation studies. The low ketoconazole release for ketoconazole observed indicated that the poloxamers had formed a gel matrix that sustained the release of ketoconazole and would therefore ensure that once daily administration of the gel was possible. The sol-gel transition test may be used as a simple and cheap alternative to viscosity testing for thermosetting formulations when expensive viscometers and rheometers are unavailable and was successfully used for this purpose.Ketoconazole is photolabile and is prone to degradation in aqueous solutions. The hydrophobic core of micelles formed in these dosage forms are believed to shield ketoconazole molecules and improve stability in aqueous solutions and acidic gels. The thermosetting gel optimised for poloxamer content was subjected to a further Central Composite Design in which sodium metabisulphite content and vehicle pH were investigated. The length of storage was used as a numeric variable and storage condition as a categoric variable at two levels to monitor the stability of the gels. The formulations were investigated at sample times of 0, 1, 2, 4 and 8 weeks at 5 °C, 25 °C and 40 °C. The use of a Central Composite Design facilitated an understanding of the interactions between input variables and their impact on the responses analysed including ketoconazole content, release at 24, 48 and 72 hours, gel pH and viscosity at 22 °C and 37 °C. Design of Experiments may be used as a rapid cost effective tool for an overall assessment of the stability of novel topical dosage forms. However, a more thorough assessment of stability may be required for product registration. Ketoconazole was found to be unstable in the acidic thermosetting gels despite the addition of antioxidant. The gels in liquid form at 5 °C and 25 °C have a low number of micelles for ketoconazole incorporation and therefore additional optimisation studies would be required to enhance the shelf-life of this product.
- Full Text:
- Date Issued: 2017
Development and implementation of health promotion activities for the prevention of adolescent pregnancies
- Authors: Chemuru, Nomsa Rutendo
- Date: 2017
- Subjects: Teenage pregnancy -- South Africa -- Makhanda , Teenage pregnancy -- Prevention -- South Africa -- Makhanda
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/5115 , vital:20776
- Description: Of the eight Millennium Development Goals (MDGs) established in 2000 by the World Health Organisation, Millennium Development Goals 5 aimed at improving maternal health by addressing the high maternal mortality rate and increasing universal access to reproductive health by 2015.Adolescent pregnancy contributes to maternal, perinatal and infant mortality and also worsens the empowerment of young girls by negatively affecting their physical, educational, social, and economic development.This is a pressing public health concern in South Africa. The reduction of adolescent pregnancy is vital for achieving the sustainable human, health social and economic development of society at large. Culturally sensitive interventions to prevent adolescent pregnancies not only integrate the communities' norms, values, practices and behavioural patterns into the intervention's design and implementation but also the historical, social and economic contexts in which they exist. Progress has been made on the research on health promotion and education in South Africa; however communities are often not consulted on the design and conduct of health promotion research projects.The aim of the study was to develop and implement culturally sensitive and appropriate health promotion activities for the prevention of adolescent pregnancy in Grahamstown, Glenmore and Ndwayana communities in the Eastern Cape, South Africa.Two community based organisations and community care workers associated with them participated in this Community Based Participatory Research using the PEN-3 cultural model. The first phase of this study involved semi-structured interviews carried out with 14 community care workers to identify factors and consequences of adolescent pregnancies in their respective communities. The audio-recorded interviews were transcribed and coded using NVivo® 2010 software. The PEN 3 cultural model was adopted in the studyto address the socio-cultural factors contributing to adolescent pregnancy in the communities. The second phase involved a series of interactive workshops with CCWs for a participatory development of the facilitator's manual. Responses from CCWs informed the design of this study's intervention strategies. A facilitator's manual was developed to implement health promotion intervention, leading to the third phase of this study. The guided implementationof the health promotion intervention for the prevention of adolescent pregnancy was carried out over a period of 14 months and evaluated in the final phase of the study. The facilitator's manual was modified based on feedback fromCCWs, on possible improvements and cultural appropriateness. Readability testing guided the final modification of the manual. According to the community care workers, there were a number of adolescents who fell pregnant in their communities each year. The CCWs identified the influence of family members, friends and other stakeholders as contributory factors to adolescent pregnancy. They identified the lack of parental support in informing and educating adolescents about sexual health. Adolescents themselves lacked the maturity to recognise the risks and consequences of adolescent pregnancy. The negative perceptions of contraception in the community were discouraging contraceptive use amongst the adolescents. However, the results showed that enablers such as home and school visits done by the community care workers can be utilised to prevent adolescent pregnancy. Other factors included lack of health promotion materials and activities with information about preventing of adolescent pregnancy, and if available, the material is in English, that the adolescents may not comprehend. Socio-economic factors such as poverty, the Child Support Grant, cross generational relationships and coerced sex further contributed to adolescent pregnancy in the communities.CCWs identified the need for a more comprehensive health promotion intervention to prevent of adolescent pregnancy. A facilitator's manual addressing the prevention of adolescent pregnancy was developed and modified through a series participatory workshops with the community care workers.The facilitator's manual was used by CCWs to conducthealth promotion activities encouraging the prevention of adolescent pregnancies within the community's clinics, schools and during home visits. Community based participatory research methods and the PEN-3cultural model were used to develop this culturally sensitive and community specific adolescent pregnancy intervention for and by the CCWs. The participatory development of the facilitator's manual and the regular interactive workshops with the CCWs were strengthened by embedding this project into the development programs of the two non-governmental organisations contributing to sustainable development programs for women and children.
- Full Text:
- Date Issued: 2017
- Authors: Chemuru, Nomsa Rutendo
- Date: 2017
- Subjects: Teenage pregnancy -- South Africa -- Makhanda , Teenage pregnancy -- Prevention -- South Africa -- Makhanda
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/5115 , vital:20776
- Description: Of the eight Millennium Development Goals (MDGs) established in 2000 by the World Health Organisation, Millennium Development Goals 5 aimed at improving maternal health by addressing the high maternal mortality rate and increasing universal access to reproductive health by 2015.Adolescent pregnancy contributes to maternal, perinatal and infant mortality and also worsens the empowerment of young girls by negatively affecting their physical, educational, social, and economic development.This is a pressing public health concern in South Africa. The reduction of adolescent pregnancy is vital for achieving the sustainable human, health social and economic development of society at large. Culturally sensitive interventions to prevent adolescent pregnancies not only integrate the communities' norms, values, practices and behavioural patterns into the intervention's design and implementation but also the historical, social and economic contexts in which they exist. Progress has been made on the research on health promotion and education in South Africa; however communities are often not consulted on the design and conduct of health promotion research projects.The aim of the study was to develop and implement culturally sensitive and appropriate health promotion activities for the prevention of adolescent pregnancy in Grahamstown, Glenmore and Ndwayana communities in the Eastern Cape, South Africa.Two community based organisations and community care workers associated with them participated in this Community Based Participatory Research using the PEN-3 cultural model. The first phase of this study involved semi-structured interviews carried out with 14 community care workers to identify factors and consequences of adolescent pregnancies in their respective communities. The audio-recorded interviews were transcribed and coded using NVivo® 2010 software. The PEN 3 cultural model was adopted in the studyto address the socio-cultural factors contributing to adolescent pregnancy in the communities. The second phase involved a series of interactive workshops with CCWs for a participatory development of the facilitator's manual. Responses from CCWs informed the design of this study's intervention strategies. A facilitator's manual was developed to implement health promotion intervention, leading to the third phase of this study. The guided implementationof the health promotion intervention for the prevention of adolescent pregnancy was carried out over a period of 14 months and evaluated in the final phase of the study. The facilitator's manual was modified based on feedback fromCCWs, on possible improvements and cultural appropriateness. Readability testing guided the final modification of the manual. According to the community care workers, there were a number of adolescents who fell pregnant in their communities each year. The CCWs identified the influence of family members, friends and other stakeholders as contributory factors to adolescent pregnancy. They identified the lack of parental support in informing and educating adolescents about sexual health. Adolescents themselves lacked the maturity to recognise the risks and consequences of adolescent pregnancy. The negative perceptions of contraception in the community were discouraging contraceptive use amongst the adolescents. However, the results showed that enablers such as home and school visits done by the community care workers can be utilised to prevent adolescent pregnancy. Other factors included lack of health promotion materials and activities with information about preventing of adolescent pregnancy, and if available, the material is in English, that the adolescents may not comprehend. Socio-economic factors such as poverty, the Child Support Grant, cross generational relationships and coerced sex further contributed to adolescent pregnancy in the communities.CCWs identified the need for a more comprehensive health promotion intervention to prevent of adolescent pregnancy. A facilitator's manual addressing the prevention of adolescent pregnancy was developed and modified through a series participatory workshops with the community care workers.The facilitator's manual was used by CCWs to conducthealth promotion activities encouraging the prevention of adolescent pregnancies within the community's clinics, schools and during home visits. Community based participatory research methods and the PEN-3cultural model were used to develop this culturally sensitive and community specific adolescent pregnancy intervention for and by the CCWs. The participatory development of the facilitator's manual and the regular interactive workshops with the CCWs were strengthened by embedding this project into the development programs of the two non-governmental organisations contributing to sustainable development programs for women and children.
- Full Text:
- Date Issued: 2017
Development and validation of an In Vitro Release Test (IVRT) to investigate the release of miconazole nitrate from topical cream formulations
- Authors: Purazi, Potiwa
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65223 , vital:28711
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Purazi, Potiwa
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65223 , vital:28711
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
Evaluation of the acceptability of ambulatory blood pressure monitoring in a semi-rural, Eastern Cape population
- Authors: Chiwanza, Farisai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59161 , vital:27447
- Description: Expected release date-April 2019
- Full Text:
- Date Issued: 2017
- Authors: Chiwanza, Farisai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59161 , vital:27447
- Description: Expected release date-April 2019
- Full Text:
- Date Issued: 2017
Formulation development, manufacture and evaluation of hydralazine hydrochloride microspheres
- Kangausaru, Shakemore Tinashe
- Authors: Kangausaru, Shakemore Tinashe
- Date: 2017
- Subjects: Hydralazine , Microspheres , Drugs Controlled release , Drugs Design , Drug development , Hypertension Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59220 , vital:27482
- Description: Despite improvements in its detection and treatment since the 1970s, hypertension is the most common and important risk factor for cardiovascular diseases. Hypertension is a chronic condition often underdiagnosed and/or inadequately treated in Sub-Saharan Africa. Recent survey results illustrate that the condition continues to contribute significantly to mortality and morbidity in adults and that it is poorly controlled in clinical practice. Hydralazine (HYD) is used either alone or in combination for the management of chronic hypertension, chronic cardiac failure and hypertensive crises. Due to its short plasma half-life of between 2 to 4 hours, HYD is normally administered two to four times daily, therefore making it a potential candidate for inclusion in sustained release formulations. The formulation of sustained release microsphere dosage forms may be useful to improve patient adherence and to achieve predictable and optimised therapeutic plasma concentrations. A stability indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the quantitation of HYD in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. UV/Vis detection method was selected as HYD contains an ultraviolet light-absorbing chromophore. The method was validated with respect to linearity and range, limits of quantitation (LOQ) and detection (LOD), accuracy, precision, sensitivity, selectivity and specificity as per International Conference on Harmonisation (ICH) guidelines. The method was applied to commercially available HYD tablets. No interfering peaks were observed from excipients used in the commercially available tablets. Preformulation studies were conducted to ensure the manufacture of high quality, stable sustained release HYD microspheres. The results revealed that there was an interaction between HYD and Carbopol® 971P, therefore Carbopol® polymers were not included during formulation studies. HYD was found to be compatible with Methocel® K100LV, Eudragit® RS PO and Avicel® 101 and HYD formulations were developed and optimised using these excipients. An oil-in-oil (o/o) solvent evaporation technique was selected for the manufacture of HYD microspheres due to its simplicity and to avoid exposure of HYD to moisture that could have been encountered if a water-in-oil (w/o) manufacturing process was used. The selection of o/o solvent evaporation technique was also based on the hydrophilicity of HYD and the polymers selected. Different grades of Methocel® and Eudragit® were selected to evaluate their effect on encapsulation efficiency (EE), in vitro release and microparticle shape and morphology. The best combination of these polymers which resulted in the desired EE, in vitro release, microparticle shape and size were then selected for formulation optimisation. A numerical optimisation approach was used to predict a formulation composition that would produce minimal HYD release initially and maximum HYD release after 12 hours of dissolution testing. The release kinetics of HYD from the manufactured microspheres were established by fitting in vitro release data to several mathematical models. The in vitro release data for the optimised formulations was best described using Higuchi model. The short-term stability of the optimised formulations was established by undertaking stability studies at 4°C, 25 °C/60 % RH and 40 °C/75 % RH. The results revealed that there was no significant change in appearance and physicochemical properties of the microspheres over a period of one month. However, long-term stability studies would be required to determine the shelf-life of the formulations. In addition, a gas chromatographic (GC) method was selected for determining residual amounts of acetone and n-hexane in the optimised formulations. GC methods were developed and optimised by evaluation of process parameters. System suitability testing was performed with respect to resolution, theoretical number of plates and selectivity. Method validation was performed with respect to linearity, range, inter- and intra-day precision, retention time (Rt) precision, limit of quantitation (LOQ) and detection (LOD). A solvent extraction method was used to analyse residual solvents in the optimised formulations. The drying process was sufficient in evaporating acetone and n-hexane from the optimised formulations. Solvent evaporation technique has been successfully used in the manufacture of HYD microspheres. The microspheres have potential for further development, scale up formulation studies and long-term stability studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Kangausaru, Shakemore Tinashe
- Date: 2017
- Subjects: Hydralazine , Microspheres , Drugs Controlled release , Drugs Design , Drug development , Hypertension Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59220 , vital:27482
- Description: Despite improvements in its detection and treatment since the 1970s, hypertension is the most common and important risk factor for cardiovascular diseases. Hypertension is a chronic condition often underdiagnosed and/or inadequately treated in Sub-Saharan Africa. Recent survey results illustrate that the condition continues to contribute significantly to mortality and morbidity in adults and that it is poorly controlled in clinical practice. Hydralazine (HYD) is used either alone or in combination for the management of chronic hypertension, chronic cardiac failure and hypertensive crises. Due to its short plasma half-life of between 2 to 4 hours, HYD is normally administered two to four times daily, therefore making it a potential candidate for inclusion in sustained release formulations. The formulation of sustained release microsphere dosage forms may be useful to improve patient adherence and to achieve predictable and optimised therapeutic plasma concentrations. A stability indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the quantitation of HYD in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. UV/Vis detection method was selected as HYD contains an ultraviolet light-absorbing chromophore. The method was validated with respect to linearity and range, limits of quantitation (LOQ) and detection (LOD), accuracy, precision, sensitivity, selectivity and specificity as per International Conference on Harmonisation (ICH) guidelines. The method was applied to commercially available HYD tablets. No interfering peaks were observed from excipients used in the commercially available tablets. Preformulation studies were conducted to ensure the manufacture of high quality, stable sustained release HYD microspheres. The results revealed that there was an interaction between HYD and Carbopol® 971P, therefore Carbopol® polymers were not included during formulation studies. HYD was found to be compatible with Methocel® K100LV, Eudragit® RS PO and Avicel® 101 and HYD formulations were developed and optimised using these excipients. An oil-in-oil (o/o) solvent evaporation technique was selected for the manufacture of HYD microspheres due to its simplicity and to avoid exposure of HYD to moisture that could have been encountered if a water-in-oil (w/o) manufacturing process was used. The selection of o/o solvent evaporation technique was also based on the hydrophilicity of HYD and the polymers selected. Different grades of Methocel® and Eudragit® were selected to evaluate their effect on encapsulation efficiency (EE), in vitro release and microparticle shape and morphology. The best combination of these polymers which resulted in the desired EE, in vitro release, microparticle shape and size were then selected for formulation optimisation. A numerical optimisation approach was used to predict a formulation composition that would produce minimal HYD release initially and maximum HYD release after 12 hours of dissolution testing. The release kinetics of HYD from the manufactured microspheres were established by fitting in vitro release data to several mathematical models. The in vitro release data for the optimised formulations was best described using Higuchi model. The short-term stability of the optimised formulations was established by undertaking stability studies at 4°C, 25 °C/60 % RH and 40 °C/75 % RH. The results revealed that there was no significant change in appearance and physicochemical properties of the microspheres over a period of one month. However, long-term stability studies would be required to determine the shelf-life of the formulations. In addition, a gas chromatographic (GC) method was selected for determining residual amounts of acetone and n-hexane in the optimised formulations. GC methods were developed and optimised by evaluation of process parameters. System suitability testing was performed with respect to resolution, theoretical number of plates and selectivity. Method validation was performed with respect to linearity, range, inter- and intra-day precision, retention time (Rt) precision, limit of quantitation (LOQ) and detection (LOD). A solvent extraction method was used to analyse residual solvents in the optimised formulations. The drying process was sufficient in evaporating acetone and n-hexane from the optimised formulations. Solvent evaporation technique has been successfully used in the manufacture of HYD microspheres. The microspheres have potential for further development, scale up formulation studies and long-term stability studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Formulation, development and evaluation of lipid nanocarriers for minocycline hydrochloride
- Authors: Ranchhod, Janeeta
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65234 , vital:28712
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Ranchhod, Janeeta
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65234 , vital:28712
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
Health promotion: approaches to dietary salt reduction
- Authors: Mushoriwa, Fadzai
- Date: 2017
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/44761 , vital:25439
- Description: Background Globally, non-communicable diseases are the leading causes of mortality and morbidity, with the majority of these occurring in low-middle income countries. The devastating consequences of non-communicable diseases could be curtailed through better management of four modifiable factors: physical inactivity; tobacco use; harmful use of alcohol; and unhealthy diets. The World Health Organisation has recommended dietary salt reduction as a cost-effective strategy in combatting the burden of NCDs. Consumer awareness and education is one of three primary strategies that have been identified by the World Health Organisation to achieve population-wide salt reduction. It involves the provision of salt reduction knowledge and the promotion of healthy salt related practices. These campaigns are a necessity in populations with high discretionary salt use such as South Africa. For these health promotion activities to succeed, they need to be developed with consideration of factors such as the environment, culture, and socio-economic standing of the intended target population. This two-phase health promotion study was conducted at St Mary’s Development and Care Centre and the Assumption Sisters Nutrition Centre. These are two community based organisations located in Grahamstown, South Africa. A needs assessment was conducted to identify the knowledge and practices of cooks and guardians from these centres on dietary salt reduction. The aim of the second phase of the study was to conduct an educational intervention and to develop a culturally appropriate and contextually specific health information intervention through a participatory process. Method: This was a qualitative study that was supported by elements of quantitative research.. The first phase of the current study was a needs assessment. The first step involved an observational phase with cooks from the centres. The aim was to observe their discretionary salt use during food preparation and to document the salt content in the processed foods available at each centre. Semi-structured interviews were then conducted, with 3 cooks and 16 guardians1 from the centres, to assess their knowledge and practices regarding salt reduction.Parents or the people responsible for the care of the children attending both centres. Guided by findings from the needs assessment phase, an educational intervention was developed. This phase involved the participatory development of three health information leaflets and a series of educational interactive sessions were conducted. Quantitative tests to assess the readability, suitability, and actionability were conducted on the leaflets. Qualitative assessment of the leaflets involved formative evaluations conducted by health care professionals, phase 1 participants, Rhodes University peer educators, an African languages and cultural expert, and a Rhodes University student wellness manager. This step was included to assess the content validity, context specificity, acceptability, and cultural appropriateness of the materials. Educational interactive sessions were guided by constructs of the Social Cognitive Theory and were conducted on three main topics: ‘Salt and my health’, ‘Reducing salt in my diet’, and ‘Reading food labels’. Results: The majority of the processed foods available at both centres contained low to medium levels of salt. Children at the centres were not provided with salt shakers on the tables during meal times. Cooks did not use measuring utensils when adding salt during meal preparation. Semistructured interviews revealed that participants lacked both declarative and procedural knowledge. In terms of declarative knowledge, they were unaware of the daily salt intake recommendations and the relationship between salt and sodium. Participants were able to identify hypertension as one of the health related consequences of high salt consumption. Most participants were responsible for purchasing groceries in their households. Their selfreported food label reading behaviours and inability to read food labels highlighted their lack of procedural knowledge. Most participants reported that they added salt during meal preparation and at mealtimes, highlighting high discretionary salt use. Some participants were also aware of cultural or religious uses of salt. The developed health information leaflets were considered to be written at a readability level appropriate for the target audience. The leaflets were also deemed to be actionable, culturally appropriate, and contextually specific and suitable materials. The educational interactive sessions were found to be interesting and informative. Conclusions: Findings from the needs assessment revealed the need for an educational intervention to address the identified gaps in the participants’ knowledge and practices regarding dietary salt reduction. The developed health information leaflets were found to be informative, culturally appropriate, and contextually specific, as planned. Interactive sessions provided an excellent platform to supply participants with concise and accurate information, increasing the possibility of improving their salt reduction related knowledge.
- Full Text:
- Date Issued: 2017
- Authors: Mushoriwa, Fadzai
- Date: 2017
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/44761 , vital:25439
- Description: Background Globally, non-communicable diseases are the leading causes of mortality and morbidity, with the majority of these occurring in low-middle income countries. The devastating consequences of non-communicable diseases could be curtailed through better management of four modifiable factors: physical inactivity; tobacco use; harmful use of alcohol; and unhealthy diets. The World Health Organisation has recommended dietary salt reduction as a cost-effective strategy in combatting the burden of NCDs. Consumer awareness and education is one of three primary strategies that have been identified by the World Health Organisation to achieve population-wide salt reduction. It involves the provision of salt reduction knowledge and the promotion of healthy salt related practices. These campaigns are a necessity in populations with high discretionary salt use such as South Africa. For these health promotion activities to succeed, they need to be developed with consideration of factors such as the environment, culture, and socio-economic standing of the intended target population. This two-phase health promotion study was conducted at St Mary’s Development and Care Centre and the Assumption Sisters Nutrition Centre. These are two community based organisations located in Grahamstown, South Africa. A needs assessment was conducted to identify the knowledge and practices of cooks and guardians from these centres on dietary salt reduction. The aim of the second phase of the study was to conduct an educational intervention and to develop a culturally appropriate and contextually specific health information intervention through a participatory process. Method: This was a qualitative study that was supported by elements of quantitative research.. The first phase of the current study was a needs assessment. The first step involved an observational phase with cooks from the centres. The aim was to observe their discretionary salt use during food preparation and to document the salt content in the processed foods available at each centre. Semi-structured interviews were then conducted, with 3 cooks and 16 guardians1 from the centres, to assess their knowledge and practices regarding salt reduction.Parents or the people responsible for the care of the children attending both centres. Guided by findings from the needs assessment phase, an educational intervention was developed. This phase involved the participatory development of three health information leaflets and a series of educational interactive sessions were conducted. Quantitative tests to assess the readability, suitability, and actionability were conducted on the leaflets. Qualitative assessment of the leaflets involved formative evaluations conducted by health care professionals, phase 1 participants, Rhodes University peer educators, an African languages and cultural expert, and a Rhodes University student wellness manager. This step was included to assess the content validity, context specificity, acceptability, and cultural appropriateness of the materials. Educational interactive sessions were guided by constructs of the Social Cognitive Theory and were conducted on three main topics: ‘Salt and my health’, ‘Reducing salt in my diet’, and ‘Reading food labels’. Results: The majority of the processed foods available at both centres contained low to medium levels of salt. Children at the centres were not provided with salt shakers on the tables during meal times. Cooks did not use measuring utensils when adding salt during meal preparation. Semistructured interviews revealed that participants lacked both declarative and procedural knowledge. In terms of declarative knowledge, they were unaware of the daily salt intake recommendations and the relationship between salt and sodium. Participants were able to identify hypertension as one of the health related consequences of high salt consumption. Most participants were responsible for purchasing groceries in their households. Their selfreported food label reading behaviours and inability to read food labels highlighted their lack of procedural knowledge. Most participants reported that they added salt during meal preparation and at mealtimes, highlighting high discretionary salt use. Some participants were also aware of cultural or religious uses of salt. The developed health information leaflets were considered to be written at a readability level appropriate for the target audience. The leaflets were also deemed to be actionable, culturally appropriate, and contextually specific and suitable materials. The educational interactive sessions were found to be interesting and informative. Conclusions: Findings from the needs assessment revealed the need for an educational intervention to address the identified gaps in the participants’ knowledge and practices regarding dietary salt reduction. The developed health information leaflets were found to be informative, culturally appropriate, and contextually specific, as planned. Interactive sessions provided an excellent platform to supply participants with concise and accurate information, increasing the possibility of improving their salt reduction related knowledge.
- Full Text:
- Date Issued: 2017
Investigation of the potency of topical corticosteroids using the vasoconstrictor assay
- Authors: Zvidzayi, Kudzayi Michael
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65279 , vital:28717
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Zvidzayi, Kudzayi Michael
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65279 , vital:28717
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
Microbial water quality monitoring of raw and treated water sources in Harare and the effect of gender in disaster management due to water related disasters
- Authors: Chirenda, Tatenda Grace
- Date: 2017
- Subjects: Drinking water Microbiology Zimbabwe Harare , Heterotrophic bacteria Zimbabwe Harare , Emergency management Zimbabwe Harare , Disasters Social aspects Zimbabwe Harare , Water quality management Zimbabwe Harare , Public health Zimbabwe Harare , Sex role Zimbabwe Harare
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59156 , vital:27444
- Description: Background - Microbial water quality monitoring is essential to the provision of potable water for domestic use. Unsafe water sources increase the risk of waterborne diseases. There is a need to raise awareness of legislature that supports management of water related disasters. Gender, education, health, and economic vulnerability contribute to the success of disaster management. Aim - This study aimed to investigate the microbial water quality of treated water in the Harare area. The study also researched the microbial water quality monitoring practices in Zimbabwe and how these contribute to the management of water borne diseases. The impact of gender, marriage, education, and disease in disaster management practices in Zimbabwe and South Africa was analysed. Method - Literature review was conducted on microbial water quality monitoring practices in Zimbabwe and legislature that supports disaster management. Practices of disaster management in Zimbabwe, and South Africa were investigated and compared. The perspective of the Harare community on the quality of their potable water was investigated through the use of a questionnaire and water quality testing was conducted using hydrogen sulphide test and R2A based heterotrophic plate count. Raw water supplying Manyame River and tap water in Harare households were assessed for microbial quality. Results and Discussion - Raw water sources were found to be contaminated by faecal matter. Household water sources had no faecal contamination, but tested positive for heterotrophic bacteria. The CFU/ml quantities obtained ranged from 1- 452 CFU/ml for all samples. The WHO guidelines for domestic water sources recommend that domestic water should have no coliforms/100 ml sample. Disaster management protocols were available in disaster prone areas such as the Matabeleland South Province. No guidelines were in place for monitoring microbial water quality as a disaster prevention method. Conclusion - The current state of treated water supplied by the Morton Jaffray Treatment Plant was found to be suitable for domestic use, but not sufficient to meet the Harare population’s needs. The need to push for legislature supporting microbial water quality monitoring was recognised. Initiating public / private partnerships in water distribution and water quality monitoring in Zimbabwe was encouraged.
- Full Text:
- Date Issued: 2017
- Authors: Chirenda, Tatenda Grace
- Date: 2017
- Subjects: Drinking water Microbiology Zimbabwe Harare , Heterotrophic bacteria Zimbabwe Harare , Emergency management Zimbabwe Harare , Disasters Social aspects Zimbabwe Harare , Water quality management Zimbabwe Harare , Public health Zimbabwe Harare , Sex role Zimbabwe Harare
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59156 , vital:27444
- Description: Background - Microbial water quality monitoring is essential to the provision of potable water for domestic use. Unsafe water sources increase the risk of waterborne diseases. There is a need to raise awareness of legislature that supports management of water related disasters. Gender, education, health, and economic vulnerability contribute to the success of disaster management. Aim - This study aimed to investigate the microbial water quality of treated water in the Harare area. The study also researched the microbial water quality monitoring practices in Zimbabwe and how these contribute to the management of water borne diseases. The impact of gender, marriage, education, and disease in disaster management practices in Zimbabwe and South Africa was analysed. Method - Literature review was conducted on microbial water quality monitoring practices in Zimbabwe and legislature that supports disaster management. Practices of disaster management in Zimbabwe, and South Africa were investigated and compared. The perspective of the Harare community on the quality of their potable water was investigated through the use of a questionnaire and water quality testing was conducted using hydrogen sulphide test and R2A based heterotrophic plate count. Raw water supplying Manyame River and tap water in Harare households were assessed for microbial quality. Results and Discussion - Raw water sources were found to be contaminated by faecal matter. Household water sources had no faecal contamination, but tested positive for heterotrophic bacteria. The CFU/ml quantities obtained ranged from 1- 452 CFU/ml for all samples. The WHO guidelines for domestic water sources recommend that domestic water should have no coliforms/100 ml sample. Disaster management protocols were available in disaster prone areas such as the Matabeleland South Province. No guidelines were in place for monitoring microbial water quality as a disaster prevention method. Conclusion - The current state of treated water supplied by the Morton Jaffray Treatment Plant was found to be suitable for domestic use, but not sufficient to meet the Harare population’s needs. The need to push for legislature supporting microbial water quality monitoring was recognised. Initiating public / private partnerships in water distribution and water quality monitoring in Zimbabwe was encouraged.
- Full Text:
- Date Issued: 2017
Preparation and evaluation of captopril - ion exchange resin complexes
- Chikukwa, Mellisa Tafadzwa Ruramai
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59146 , vital:27441
- Description: Restricted access-thesis embargoed for 2 years
- Full Text:
- Date Issued: 2017
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59146 , vital:27441
- Description: Restricted access-thesis embargoed for 2 years
- Full Text:
- Date Issued: 2017
Sorptive and microbial properties of low-cost adsorbents used in the extraction of ciprofloxacin and isoniazid from aqueous solution
- Authors: Dube, Cyril Simbarashe
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/59178 , vital:27450
- Description: This work describes how coal fly ash (FA), kaolinite, perlite, talc and vermiculite were used to remove ciprofloxacin and isoniazid from aqueous solutions. The adsorptive features of the adsorbents were evaluated for ciprofloxacin and isoniazid with regards to the effects of contact time, pH, solid/liquid ratio and antibiotic concentration. All adsorbents were sterilised by dry heat before use to avoid the proliferation of antimicrobial resistance by the bacteria present on the adsorbents during experiments. The regression correlation coefficients indicate that the linearised form of the Langmuir isotherm gives the best fit for the sorption of both antibiotics onto FA and talc, ciprofloxacin onto kaolinite, and isoniazid onto perlite and vermiculite with R2 values ranging from 0.908 - 0.999. The linearised form of the Freundlich isotherm best describes the sorption of ciprofloxacin onto vermiculite and isoniazid onto kaolinite with R2 values of 0.999 for both. The linearised form of the Temkin isotherm best describes the sorption of ciprofloxacin onto perlite with an R2 = 0.997. The values of the Freundlich exponent, 1/n, range from 0.221 - 0.998, indicating a favourable adsorption of ciprofloxacin and isoniazid onto the adsorbents. The heat of sorption, B, calculated from the Temkin plots has values ranging from 0.018 - 10.460 J/mol, indicating a physical adsorption process (physisorption). Adsorption equilibrium on all adsorbents was achieved after 30 min for both antibiotics and the kinetic data obtained conforms best to the pseudo-second order equation with R2 values ranging from 0.998 - 0.999. The removal of ciprofloxacin and isoniazid by all adsorbents except FA was strongly influenced by the pH suggesting that electrostatic interactions play a major role in the adsorption processes. All adsorbents except FA removed showed excellent adsorption of ciprofloxacin from aqueous solutions with all of them achieving removals ranging from 80 - 99%. The adsorbents were less efficient in removing isoniazid and kaolinite gave the highest removal of 55 %. Furthermore, the microbial quality of the adsorbents was investigated and the results revealed that kaolinite, talc, perlite and vermiculite were heavily contaminated with microorganisms. FA was sterile. The fungi isolated from the mineral adsorbents were in concentrations ranging from 2.13 x 106 to 1.25 x 107 CFU/g and were mostly moulds; Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Cladosporium spp. and Rhizopus oryzae. One yeast was isolated and was identified as Candida albicans. The bacteria identified were in concentrations ranging from 4.96 x 106 - 1.19 x 109 CFU/g. E. coli, Enterobacter cloacae, Exiguobacterium spp., Pseudomonas aeruginosa, Bacillus spp. and Serratia liquefaciens. The leachability index (LI) values obtained for adsorbents indicated that it is highly unlikely that microorganisms could be leached out of the adsorbents by rain. Heat inactivation of the microorganisms at a 105 °C was totally unsuccessful. However, it was established that a dry heat dose of 160 °C for at least 15 min was sufficient to eradicate all microorganisms present in the adsorbents. The D-values for coliform bacteria from all samples were very similar ranging from 1.7-2.2 min indicating homogeneity in heat resistance by the microorganisms. The Pseudomonas aureginosa isolated had a D-value of 2.2 min. The fungi isolated from the samples had D-values ranging from 2.1-3.2 min.
- Full Text:
- Date Issued: 2017
- Authors: Dube, Cyril Simbarashe
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/59178 , vital:27450
- Description: This work describes how coal fly ash (FA), kaolinite, perlite, talc and vermiculite were used to remove ciprofloxacin and isoniazid from aqueous solutions. The adsorptive features of the adsorbents were evaluated for ciprofloxacin and isoniazid with regards to the effects of contact time, pH, solid/liquid ratio and antibiotic concentration. All adsorbents were sterilised by dry heat before use to avoid the proliferation of antimicrobial resistance by the bacteria present on the adsorbents during experiments. The regression correlation coefficients indicate that the linearised form of the Langmuir isotherm gives the best fit for the sorption of both antibiotics onto FA and talc, ciprofloxacin onto kaolinite, and isoniazid onto perlite and vermiculite with R2 values ranging from 0.908 - 0.999. The linearised form of the Freundlich isotherm best describes the sorption of ciprofloxacin onto vermiculite and isoniazid onto kaolinite with R2 values of 0.999 for both. The linearised form of the Temkin isotherm best describes the sorption of ciprofloxacin onto perlite with an R2 = 0.997. The values of the Freundlich exponent, 1/n, range from 0.221 - 0.998, indicating a favourable adsorption of ciprofloxacin and isoniazid onto the adsorbents. The heat of sorption, B, calculated from the Temkin plots has values ranging from 0.018 - 10.460 J/mol, indicating a physical adsorption process (physisorption). Adsorption equilibrium on all adsorbents was achieved after 30 min for both antibiotics and the kinetic data obtained conforms best to the pseudo-second order equation with R2 values ranging from 0.998 - 0.999. The removal of ciprofloxacin and isoniazid by all adsorbents except FA was strongly influenced by the pH suggesting that electrostatic interactions play a major role in the adsorption processes. All adsorbents except FA removed showed excellent adsorption of ciprofloxacin from aqueous solutions with all of them achieving removals ranging from 80 - 99%. The adsorbents were less efficient in removing isoniazid and kaolinite gave the highest removal of 55 %. Furthermore, the microbial quality of the adsorbents was investigated and the results revealed that kaolinite, talc, perlite and vermiculite were heavily contaminated with microorganisms. FA was sterile. The fungi isolated from the mineral adsorbents were in concentrations ranging from 2.13 x 106 to 1.25 x 107 CFU/g and were mostly moulds; Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Cladosporium spp. and Rhizopus oryzae. One yeast was isolated and was identified as Candida albicans. The bacteria identified were in concentrations ranging from 4.96 x 106 - 1.19 x 109 CFU/g. E. coli, Enterobacter cloacae, Exiguobacterium spp., Pseudomonas aeruginosa, Bacillus spp. and Serratia liquefaciens. The leachability index (LI) values obtained for adsorbents indicated that it is highly unlikely that microorganisms could be leached out of the adsorbents by rain. Heat inactivation of the microorganisms at a 105 °C was totally unsuccessful. However, it was established that a dry heat dose of 160 °C for at least 15 min was sufficient to eradicate all microorganisms present in the adsorbents. The D-values for coliform bacteria from all samples were very similar ranging from 1.7-2.2 min indicating homogeneity in heat resistance by the microorganisms. The Pseudomonas aureginosa isolated had a D-value of 2.2 min. The fungi isolated from the samples had D-values ranging from 2.1-3.2 min.
- Full Text:
- Date Issued: 2017
Studies in the thiophenol mediated substitution and reductive dehalogenation of 3 bromoacetylcoumarins
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017
Taste masking of clarithromycin with ion exchange resins
- Authors: Ntemi, Pascal Vitalis
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65178 , vital:28701
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Ntemi, Pascal Vitalis
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65178 , vital:28701
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
The applicability of anaerobically digested pasteurized pit latrine faecal sludge as a fertilizer to grow radish and garden cress
- Authors: Madikizela, Phindile
- Date: 2017
- Subjects: Sewage sludge as fertilizer , Sewage sludge digestion , Sewage Purification Anaerobic treatment
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59235 , vital:27487
- Description: Pit latrine faecal sludge was recovered from numerous pit latrines in Hlalani Township, Grahamstown, South Africa. This material was used to prepare a fertilizer to demonstrate the value that could be captured from faecal sludge. Further anaerobic digestion, together with a co-feed demonstrated the potential of faecal sludge to produce low cost fertilizer that could be used to grow food crops. Biogas recovered from the anaerobic digester could be used to pasteurize its effluent, although effective biogas recovery and storage needs to be further addressed. Investigating the microbial community of the different depths of the pit latrine through molecular techniques showed that the fermenting bacteria family Clostridiaceae was the most commonly identified family throughout the different depths of the pit latrine, and that the microbial community within pit latrines was very diverse with bacterial families that are involved in nitrogen fixation, denitrification, and iron and sulphate reduction. Additionally, most of the bacterial families that dominated the seven studied pit latrines had members that were known human pathogens (Mycobacteriaceae, Dermatophilaceae Peptostreptococcaceae, Micrococcaceae, Staphylococcaceae, Leptospiraceae, Listeriaceae, Bradyrhizobiaceae and Brucellaceae). Effluent from a wastewater treatment works was selected as a co-feed to augment biogas production. The most successful faecal sludge and co-feed combination was shown to be the one made up of 33% and 66% pit latrine faecal sludge. 180 L of this effluent mixture generated 285 L of biogas over 45 days of anaerobic digestion (29±2°C). However, the recovered quantities were insufficient for pasteurization as 650 L of biogas was required to pasteurize 300 g of faecal sludge for 1 hour at 70±2°C. Therefore, liquid petroleum gas (LPG) was used as an alternative heating energy source. Anaerobic digestion and pasteurization rendered the faecal sludge safe for application as a fertilizer as the quality of the faecal sludge after treatment by anaerobic digestion and pasteurization was within the microbiological (Escherichia coli, Salmonella spp, Enterococcus faecium and helminth eggs) and trace element restrictions (Pb, Ni, Cr, Mo, As, Cu, Mn, Fe, Cd and Hg) of sludge application in agriculture as stipulated by the WHO and the South African Guidelines for Sludge Use in Agriculture. Radish (Raphanus sativus spp) and garden cress (Lepidium sativum) were cultivated to demonstrate the effectiveness of the anaerobically digested and pasteurized pit latrine faecal sludge as a fertilizer. Diluting the fertilizer prepared from faecal sludge did not reduce its efficacy and was comparable to the synthetic fertilizer used as a control in the growth trials in terms of the plant fresh weight, dry weight and plant height. Finally, the exposure to the current state of pit latrines in Hlalani Township provided an incentive to develop a new tool to address sanitation service delivery skill shortage (artisans, plant operation and maintenance workers, and sanitation and hygiene facilitators) through the use of volunteers. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Madikizela, Phindile
- Date: 2017
- Subjects: Sewage sludge as fertilizer , Sewage sludge digestion , Sewage Purification Anaerobic treatment
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59235 , vital:27487
- Description: Pit latrine faecal sludge was recovered from numerous pit latrines in Hlalani Township, Grahamstown, South Africa. This material was used to prepare a fertilizer to demonstrate the value that could be captured from faecal sludge. Further anaerobic digestion, together with a co-feed demonstrated the potential of faecal sludge to produce low cost fertilizer that could be used to grow food crops. Biogas recovered from the anaerobic digester could be used to pasteurize its effluent, although effective biogas recovery and storage needs to be further addressed. Investigating the microbial community of the different depths of the pit latrine through molecular techniques showed that the fermenting bacteria family Clostridiaceae was the most commonly identified family throughout the different depths of the pit latrine, and that the microbial community within pit latrines was very diverse with bacterial families that are involved in nitrogen fixation, denitrification, and iron and sulphate reduction. Additionally, most of the bacterial families that dominated the seven studied pit latrines had members that were known human pathogens (Mycobacteriaceae, Dermatophilaceae Peptostreptococcaceae, Micrococcaceae, Staphylococcaceae, Leptospiraceae, Listeriaceae, Bradyrhizobiaceae and Brucellaceae). Effluent from a wastewater treatment works was selected as a co-feed to augment biogas production. The most successful faecal sludge and co-feed combination was shown to be the one made up of 33% and 66% pit latrine faecal sludge. 180 L of this effluent mixture generated 285 L of biogas over 45 days of anaerobic digestion (29±2°C). However, the recovered quantities were insufficient for pasteurization as 650 L of biogas was required to pasteurize 300 g of faecal sludge for 1 hour at 70±2°C. Therefore, liquid petroleum gas (LPG) was used as an alternative heating energy source. Anaerobic digestion and pasteurization rendered the faecal sludge safe for application as a fertilizer as the quality of the faecal sludge after treatment by anaerobic digestion and pasteurization was within the microbiological (Escherichia coli, Salmonella spp, Enterococcus faecium and helminth eggs) and trace element restrictions (Pb, Ni, Cr, Mo, As, Cu, Mn, Fe, Cd and Hg) of sludge application in agriculture as stipulated by the WHO and the South African Guidelines for Sludge Use in Agriculture. Radish (Raphanus sativus spp) and garden cress (Lepidium sativum) were cultivated to demonstrate the effectiveness of the anaerobically digested and pasteurized pit latrine faecal sludge as a fertilizer. Diluting the fertilizer prepared from faecal sludge did not reduce its efficacy and was comparable to the synthetic fertilizer used as a control in the growth trials in terms of the plant fresh weight, dry weight and plant height. Finally, the exposure to the current state of pit latrines in Hlalani Township provided an incentive to develop a new tool to address sanitation service delivery skill shortage (artisans, plant operation and maintenance workers, and sanitation and hygiene facilitators) through the use of volunteers. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
The development, manufacture and characterisation of niosomes intended to deliver nevirapine to the brain
- Authors: Witika, Bwalya Angel
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65257 , vital:28715
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Witika, Bwalya Angel
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65257 , vital:28715
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
Workplace health promotion: a case of Rhodes University support staff
- Chigumete, Tinatsei Gabriella
- Authors: Chigumete, Tinatsei Gabriella
- Date: 2017
- Subjects: Rhodes University -- Employees -- Health and hygiene , Employee health promotion -- South Africa -- Makhanda
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/44509 , vital:25414
- Description: Background: Non-communicable diseases are rapidly advancing as leading causes of morbidity and mortality across social classes, exerting pressure on existing financial, organizational, and human resources. Health promotion is a common practice in the prevention of noncommunicable diseases, but workplace health promotion has not yet been well established in many workplaces. Identification of past workplace initiatives and exploring their facilitating and limiting factors is thus important to take into consideration when planning future initiatives. Well-informed and guided workplace health promotion initiatives are essential to improve the general health of staff, and these also need to take the broader cultural, socioeconomic, and environmental factors influencing non-communicable diseases in the target population into account. This two-phase study was conducted at Rhodes University. A needs assessment was conducted to identify current policies and practices of workplace health promotion and to identify any shortcomings of the initiatives that have previously been attempted to raise awareness of non-communicable diseases at Rhodes University. The second phase of this project aimed to address concerns raised in the first phase through a health promotion initiative for support staff that focuses on the prevention of noncommunicable diseases through heart healthy diets and physical activity. Method: The first phase of the current study involved working with the support staff and key stakeholders. Using the participatory action research approach and the PRECEDE-PROCEED model to guide the research, 11 semi-structured interviews with key stakeholders and 10 focus group discussions were conducted with support staff members to identify factors affecting workplace health promotion. Participant opinions on how to improve these initiatives were sought. The participants were asked to identify areas on which the intended intervention should focus, as well as to identify their preferred means of communicating health messages. During this phase, a group of support staff members who volunteered their involvement in the design and delivery of the educational intervention was also identified. They chose to go by the name, the Health Awareness Group.In an interim phase of the study, three health information leaflets informed by the results from the above activities were designed. These leaflets underwent a series of qualitative evaluations by other health professionals, a culture and African languages expert, and the Health Awareness Group, to assess content validity, context specificity, and cultural appropriateness for the target group. A series of quantitative tests for readability, suitability, and actionability was also conducted. The health information leaflets were then used as written materials in the educational intervention of the project. Members of the Health Awareness Group were also trained as peer educators through a series of workshops. This enabled them to promote and raise awareness of heart healthy diets and physical activity to others in the workplace. Workshops were participatory in nature and were guided by the Social Cognitive Theory. They were also equipped with the completed health information leaflets to distribute to their peers and to use as reference sources of information when needed. Results: Participants in the semi-structured interviews reported that some health promotion initiatives have previously been attempted and advertised to support staff, but the turnout was poor and most staff did not seem to understand the health benefits of these initiatives. The support staff, in turn, stated that most health talks were conducted in English, contained medical jargon, and that they would have preferred these initiatives either to be simplified or presented in their home language, and to display cultural sensitivity. Support staff have also reported that advertisements were too cliche to elicit their interest. They also suggested incentivising initiatives for better participation. Another key suggestion was to facilitate these initiatives in the university departments they work or other convenient venues, rather than at central venues. It was also suggested that these initiatives be part of the work calendar, as they are often 'impromptu' and, as a result, staff members did not have enough notice to take time off work. Several staff members requested 're-runs of these initiatives because one-time show cases are often inadequate'. Colourful visual representations on posters or leaflets, short plays or films were also proposed as modes of delivering health information. During the design of the material to be used for this project's intended intervention, the health information leaflets were deemed readable, suitable, actionable, context-specific, and culturally appropriate. Workshops conducted during Phase 2 of the study proved to be valuable in training peer educators. Members of the Health Awareness Group also deemed the workshops useful, and reported their readiness to be agents of change in the workplace. Conclusions: Based on the input of key stakeholders and support staff, health promotion policies and protocols for non-communicable diseases have not yet been developed. Health promotion initiatives, especially for support staff, that address non-communicable diseases have previously been attempted at the university but were not well-received. Factors affecting workplace health promotion were identified. Knowledge of these factors was useful in designing and tailoring the written educational materials and the educational intervention to the needs of the support staff and to redress the deficiencies of previous initiatives. The health leaflets were deemed appropriate for use by the target population. They addressed pertinent information needs. The health information leaflets and workshops were useful in equipping the Health Awareness Group with knowledge on heart healthy diets and promotion of physical activity. Continued the involvement of representatives from the Human Resources and Wellness offices will assist in ensuring the sustainability of this workplace health initiative.
- Full Text:
- Date Issued: 2017
- Authors: Chigumete, Tinatsei Gabriella
- Date: 2017
- Subjects: Rhodes University -- Employees -- Health and hygiene , Employee health promotion -- South Africa -- Makhanda
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/44509 , vital:25414
- Description: Background: Non-communicable diseases are rapidly advancing as leading causes of morbidity and mortality across social classes, exerting pressure on existing financial, organizational, and human resources. Health promotion is a common practice in the prevention of noncommunicable diseases, but workplace health promotion has not yet been well established in many workplaces. Identification of past workplace initiatives and exploring their facilitating and limiting factors is thus important to take into consideration when planning future initiatives. Well-informed and guided workplace health promotion initiatives are essential to improve the general health of staff, and these also need to take the broader cultural, socioeconomic, and environmental factors influencing non-communicable diseases in the target population into account. This two-phase study was conducted at Rhodes University. A needs assessment was conducted to identify current policies and practices of workplace health promotion and to identify any shortcomings of the initiatives that have previously been attempted to raise awareness of non-communicable diseases at Rhodes University. The second phase of this project aimed to address concerns raised in the first phase through a health promotion initiative for support staff that focuses on the prevention of noncommunicable diseases through heart healthy diets and physical activity. Method: The first phase of the current study involved working with the support staff and key stakeholders. Using the participatory action research approach and the PRECEDE-PROCEED model to guide the research, 11 semi-structured interviews with key stakeholders and 10 focus group discussions were conducted with support staff members to identify factors affecting workplace health promotion. Participant opinions on how to improve these initiatives were sought. The participants were asked to identify areas on which the intended intervention should focus, as well as to identify their preferred means of communicating health messages. During this phase, a group of support staff members who volunteered their involvement in the design and delivery of the educational intervention was also identified. They chose to go by the name, the Health Awareness Group.In an interim phase of the study, three health information leaflets informed by the results from the above activities were designed. These leaflets underwent a series of qualitative evaluations by other health professionals, a culture and African languages expert, and the Health Awareness Group, to assess content validity, context specificity, and cultural appropriateness for the target group. A series of quantitative tests for readability, suitability, and actionability was also conducted. The health information leaflets were then used as written materials in the educational intervention of the project. Members of the Health Awareness Group were also trained as peer educators through a series of workshops. This enabled them to promote and raise awareness of heart healthy diets and physical activity to others in the workplace. Workshops were participatory in nature and were guided by the Social Cognitive Theory. They were also equipped with the completed health information leaflets to distribute to their peers and to use as reference sources of information when needed. Results: Participants in the semi-structured interviews reported that some health promotion initiatives have previously been attempted and advertised to support staff, but the turnout was poor and most staff did not seem to understand the health benefits of these initiatives. The support staff, in turn, stated that most health talks were conducted in English, contained medical jargon, and that they would have preferred these initiatives either to be simplified or presented in their home language, and to display cultural sensitivity. Support staff have also reported that advertisements were too cliche to elicit their interest. They also suggested incentivising initiatives for better participation. Another key suggestion was to facilitate these initiatives in the university departments they work or other convenient venues, rather than at central venues. It was also suggested that these initiatives be part of the work calendar, as they are often 'impromptu' and, as a result, staff members did not have enough notice to take time off work. Several staff members requested 're-runs of these initiatives because one-time show cases are often inadequate'. Colourful visual representations on posters or leaflets, short plays or films were also proposed as modes of delivering health information. During the design of the material to be used for this project's intended intervention, the health information leaflets were deemed readable, suitable, actionable, context-specific, and culturally appropriate. Workshops conducted during Phase 2 of the study proved to be valuable in training peer educators. Members of the Health Awareness Group also deemed the workshops useful, and reported their readiness to be agents of change in the workplace. Conclusions: Based on the input of key stakeholders and support staff, health promotion policies and protocols for non-communicable diseases have not yet been developed. Health promotion initiatives, especially for support staff, that address non-communicable diseases have previously been attempted at the university but were not well-received. Factors affecting workplace health promotion were identified. Knowledge of these factors was useful in designing and tailoring the written educational materials and the educational intervention to the needs of the support staff and to redress the deficiencies of previous initiatives. The health leaflets were deemed appropriate for use by the target population. They addressed pertinent information needs. The health information leaflets and workshops were useful in equipping the Health Awareness Group with knowledge on heart healthy diets and promotion of physical activity. Continued the involvement of representatives from the Human Resources and Wellness offices will assist in ensuring the sustainability of this workplace health initiative.
- Full Text:
- Date Issued: 2017
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