Modification and application of the decentralised wastewater treatment technology for greywater treatment to reduce water needs
- Authors: Ngqwala, Nosiphiwe Patience
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/193509 , vital:45338
- Description: Water is a scarce resource that is being acknowledged as a limiting factor to further social- economic growth and development. Demand for freshwater is increasing with corresponding increases in human population, industrial and agricultural activities. Alternative sources, such as greywater and rainwater are often polluted. Though greywater can be used for non-potable purposes, such as irrigation, it still requires some measures of treatment to improve its quality. To improve on greywater quality to facilitate its reuse, decentralised wastewater treatment technologies carry a great potential as complementary and alternative means of wastewater management particularly in peri-urban areas. Five research goals are addressed in this thesis: (i) to monitor the performance of Fly Ash Lime Filter Tower (FLFT) in the treatment of greywater; (ii) to modify the Fly Ash Lime Filter Tower in the treatment of greywater in order to reduce the pH of the greywater, and improved on the reduction of chemical oxygen demand (COD) and coliform counts; (iii) to investigate the potential of the reuse of greywater for irrigation; (iv) to undertake a techno analysis of the FLFT system for commercial use; and (v) to evaluate the use of hydrogen-sulphide (H2S) test kit to monitor faecal contamination of various water sources using a multidisciplinary approach. The modification of the FLFT indicated good treatment efficiency, reducing the concentrations of COD, chlorides, nitrates, ammonia and sulphate by 82.6%, 60.4%, 72.9%, 60.5%, and 53.9%, respectively; while the average pH was at 8.3. Greywater contains nutrients that are beneficial to the growth of most plants. Growth variables included biomass, stem height, number of leaves and number of vegetables harvested. Soil analysis showed no effects of the treated greywater on soil physico-chemical and microbial quality with bulk density 2.0g/cm3, average pH 7.4, total phosphorus 0.16mg/L 8, faecal coliform 0.3 CFU/100 ml. The tomatoes had high biomass and dry weight (150 g; 33g) than beetroot (35 g; 15 g). Crops irrigated with greywater significantly grew faster compared with those irrigated with tap water. The community approach highlighted the value of knowledge management in greywater reuse. It highlighted the importance of creating an institutional knowledge in water management using the H2S kit. The techno-economic analysis was used to evaluate key factors and the activities that are relevant to develop a sustainable FLFT in order to gain insights into the possibility of developing, and incorporating a business model framework to support decision making in value creation and value capturing during the research and the scaling up of the system. By this, a long term perspective to accomplish sustainable FLFT service businesses can be achieved. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
- Authors: Ngqwala, Nosiphiwe Patience
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/193509 , vital:45338
- Description: Water is a scarce resource that is being acknowledged as a limiting factor to further social- economic growth and development. Demand for freshwater is increasing with corresponding increases in human population, industrial and agricultural activities. Alternative sources, such as greywater and rainwater are often polluted. Though greywater can be used for non-potable purposes, such as irrigation, it still requires some measures of treatment to improve its quality. To improve on greywater quality to facilitate its reuse, decentralised wastewater treatment technologies carry a great potential as complementary and alternative means of wastewater management particularly in peri-urban areas. Five research goals are addressed in this thesis: (i) to monitor the performance of Fly Ash Lime Filter Tower (FLFT) in the treatment of greywater; (ii) to modify the Fly Ash Lime Filter Tower in the treatment of greywater in order to reduce the pH of the greywater, and improved on the reduction of chemical oxygen demand (COD) and coliform counts; (iii) to investigate the potential of the reuse of greywater for irrigation; (iv) to undertake a techno analysis of the FLFT system for commercial use; and (v) to evaluate the use of hydrogen-sulphide (H2S) test kit to monitor faecal contamination of various water sources using a multidisciplinary approach. The modification of the FLFT indicated good treatment efficiency, reducing the concentrations of COD, chlorides, nitrates, ammonia and sulphate by 82.6%, 60.4%, 72.9%, 60.5%, and 53.9%, respectively; while the average pH was at 8.3. Greywater contains nutrients that are beneficial to the growth of most plants. Growth variables included biomass, stem height, number of leaves and number of vegetables harvested. Soil analysis showed no effects of the treated greywater on soil physico-chemical and microbial quality with bulk density 2.0g/cm3, average pH 7.4, total phosphorus 0.16mg/L 8, faecal coliform 0.3 CFU/100 ml. The tomatoes had high biomass and dry weight (150 g; 33g) than beetroot (35 g; 15 g). Crops irrigated with greywater significantly grew faster compared with those irrigated with tap water. The community approach highlighted the value of knowledge management in greywater reuse. It highlighted the importance of creating an institutional knowledge in water management using the H2S kit. The techno-economic analysis was used to evaluate key factors and the activities that are relevant to develop a sustainable FLFT in order to gain insights into the possibility of developing, and incorporating a business model framework to support decision making in value creation and value capturing during the research and the scaling up of the system. By this, a long term perspective to accomplish sustainable FLFT service businesses can be achieved. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
Synthesis and biological evaluation of truncated sarganaphthoquinoic acid derivatives as Hsp90 inhibitors
- Authors: Chiwakata, Maynard T
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64708 , vital:28594
- Description: Hsp90 inhibition has been at the centre of attention in current research due to the possibility of “cracking down” on the entire process leading to the development of malignant cancers. Small underlying principles common in all types of cancers have been determined that govern the transformation of normal human cells into cancerous cells, with all relying on the ATPase activity of Hsp90 protein. Hsp90 protein is therefore an attractive drug target that if successfully inhibited can result in the remission of cancer tumours by one form of treatment. To date, no Hsp90 inhibitor has been sanctioned for cancer treatment as most are still in clinical development. Our research was therefore inspired by reports that indicated the potential of quinones / naphthoquinones to act as Hsp90 inhibitors. Preliminary results of a few selected marine natural product quinone systems i.e. sargaquinoic acid (SQA) (2.47) and lapachol (3.6) showed moderate cytotoxicity and weak interactions with the Hsp90 molecular chaperone, and evidence suggested C-terminal binding of these molecules. No correlation has been determined yet between cytotoxicity and Hsp90 inhibition, hence we aimed to develop natural product inspired molecules that exhibit both cytotoxic and Hsp90 inhibition properties. Due to limited amounts of the natural product that can be acquired from natural sources, synthetic analogues were opted for. Isolation of a few selected quinones was conducted to have material that could be used in biological assays. For structural modifications, a series of truncated naphthoquinone systems were prepared adopting the sarganaphthoquinoic acid (3.5) scaffold. The naphthoquinones were prepared via Diels-Alder reactions of relevant benzoquinones with myrcene, followed by aromatization reactions using MnO2. Various alkyl and aryl amines were then coupled to the C-2/3 position of the naphthoquinone using Michael’s addition reactions. Tricyclic naphthoquinones were also synthesized from reactions with hypotaurine and citral. Design of the analogues incorporated functionalities from known Hsp90 inhibitors e.g. geldanamycin (2.28) and its analogues. Preliminary results obtained showed that coupling of naphthoquinones with aryl-amines resulted in the most cytotoxic compounds (4.14-4.19) with IC50 values as low as 0.3 μM against Hs578T breast cancer carcinoma (triple negative). Most of the alkyl amines (4.20-4.25) had IC50 values greater than 50 μM except for 4.20 and 4.21 that showed IC50 values of 7.6 μM and 2.6 μM respectively. Tricyclic naphthoquinones (4.28-4.29) showed moderate cytotoxic activity of approximately 10 μM. Hsp90 inhibition was assessed by client protein degradation assays, of which SQA (2.47), showed the best Hsp90 inhibition properties, followed by compound 4.20. The most cytotoxic arylamino-naphthoquinone (4.16) and tricyclic naphthoquinones (4.28-4.29) showed only moderate inhibition. None of the compounds led to Hsp70 induction, suggesting possible binding to the C-terminus of Hsp90. Interactions at the binding site were assessed by molecular docking studies and saturation transfer difference (STD) NMR. Docking studies were conducted on the N-terminus of Hsp90 and better binding was observed for arylamino naphthoquinones (4.14-4.19) than for other series of compounds. Unfortunately, the co-crystal structure for the C-terminus of Hsp90 is unavailable, hence docking study comparisons on both domains could not be conducted. However, STD NMR offered a platform to assess binding interactions between the naphthoquinones and the N- or C-terminal domains of Hsp90. However no interactions were observed at both the N- and C- termini of Hsp90 due to either weak binding of ligands to the protein or poor water solubility of the ligands. From these preliminary results, naphthoquinones bind to Hsp90 protein but conclusive remarks to which terminal domain they bind to could not be made. The best candidate from amongst the series of naphthoquinones prepared that showed moderate cytotoxicity and promising Hsp90 inhibition was compound 4.20. We therefore succeeded in developing a new series of naphthoquinones that possess moderate cytotoxicity and show Hsp90 inhibition.
- Full Text:
- Authors: Chiwakata, Maynard T
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64708 , vital:28594
- Description: Hsp90 inhibition has been at the centre of attention in current research due to the possibility of “cracking down” on the entire process leading to the development of malignant cancers. Small underlying principles common in all types of cancers have been determined that govern the transformation of normal human cells into cancerous cells, with all relying on the ATPase activity of Hsp90 protein. Hsp90 protein is therefore an attractive drug target that if successfully inhibited can result in the remission of cancer tumours by one form of treatment. To date, no Hsp90 inhibitor has been sanctioned for cancer treatment as most are still in clinical development. Our research was therefore inspired by reports that indicated the potential of quinones / naphthoquinones to act as Hsp90 inhibitors. Preliminary results of a few selected marine natural product quinone systems i.e. sargaquinoic acid (SQA) (2.47) and lapachol (3.6) showed moderate cytotoxicity and weak interactions with the Hsp90 molecular chaperone, and evidence suggested C-terminal binding of these molecules. No correlation has been determined yet between cytotoxicity and Hsp90 inhibition, hence we aimed to develop natural product inspired molecules that exhibit both cytotoxic and Hsp90 inhibition properties. Due to limited amounts of the natural product that can be acquired from natural sources, synthetic analogues were opted for. Isolation of a few selected quinones was conducted to have material that could be used in biological assays. For structural modifications, a series of truncated naphthoquinone systems were prepared adopting the sarganaphthoquinoic acid (3.5) scaffold. The naphthoquinones were prepared via Diels-Alder reactions of relevant benzoquinones with myrcene, followed by aromatization reactions using MnO2. Various alkyl and aryl amines were then coupled to the C-2/3 position of the naphthoquinone using Michael’s addition reactions. Tricyclic naphthoquinones were also synthesized from reactions with hypotaurine and citral. Design of the analogues incorporated functionalities from known Hsp90 inhibitors e.g. geldanamycin (2.28) and its analogues. Preliminary results obtained showed that coupling of naphthoquinones with aryl-amines resulted in the most cytotoxic compounds (4.14-4.19) with IC50 values as low as 0.3 μM against Hs578T breast cancer carcinoma (triple negative). Most of the alkyl amines (4.20-4.25) had IC50 values greater than 50 μM except for 4.20 and 4.21 that showed IC50 values of 7.6 μM and 2.6 μM respectively. Tricyclic naphthoquinones (4.28-4.29) showed moderate cytotoxic activity of approximately 10 μM. Hsp90 inhibition was assessed by client protein degradation assays, of which SQA (2.47), showed the best Hsp90 inhibition properties, followed by compound 4.20. The most cytotoxic arylamino-naphthoquinone (4.16) and tricyclic naphthoquinones (4.28-4.29) showed only moderate inhibition. None of the compounds led to Hsp70 induction, suggesting possible binding to the C-terminus of Hsp90. Interactions at the binding site were assessed by molecular docking studies and saturation transfer difference (STD) NMR. Docking studies were conducted on the N-terminus of Hsp90 and better binding was observed for arylamino naphthoquinones (4.14-4.19) than for other series of compounds. Unfortunately, the co-crystal structure for the C-terminus of Hsp90 is unavailable, hence docking study comparisons on both domains could not be conducted. However, STD NMR offered a platform to assess binding interactions between the naphthoquinones and the N- or C-terminal domains of Hsp90. However no interactions were observed at both the N- and C- termini of Hsp90 due to either weak binding of ligands to the protein or poor water solubility of the ligands. From these preliminary results, naphthoquinones bind to Hsp90 protein but conclusive remarks to which terminal domain they bind to could not be made. The best candidate from amongst the series of naphthoquinones prepared that showed moderate cytotoxicity and promising Hsp90 inhibition was compound 4.20. We therefore succeeded in developing a new series of naphthoquinones that possess moderate cytotoxicity and show Hsp90 inhibition.
- Full Text:
The design and evaluation of targeted patient-centred health information to improve knowledge and behavioural outcomes in tuberculosis patients with limited literacy
- Authors: Patel, Sonal
- Date: 2015
- Subjects: Tuberculosis Patients , Health literacy , Patient education , Communication in medicine , Picture-writing
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194071 , vital:45420 , DOI 10.21504/10962/194071
- Description: South Africa carries a significant TB burden as evidenced in the 2013 statistics which report 450 000 new active TB cases and 890 000 TB-related mortalities. For successful treatment outcomes, 90% adherence is necessary, but many patients prematurely discontinue treatment due to poor knowledge and understanding of their complex TB medicines. Patient education is pivotal in improving knowledge, health literacy and behavioural outcomes such as health information seeking, self-efficacy and adherence. In the under-resourced South African healthcare system, time and capacity to adequately counsel patients are limited. The value of written medicine information (WMI) to supplement the verbal information provided by healthcare professionals (HCPs) has been widely investigated but minimal South African research is available. Current WMI distributed in South Africa is mainly generated by pharmaceutical manufacturers and is complex, incomprehensible and undesirable to patients. TB-related WMI focuses mainly on the disease, with little information relating to TB medicines and their use. The overall aim of this project was to improve patient knowledge about their TB medicines through the use of a simple illustrated patient information leaflet (PIL). Objectives to achieve this aim included: investigation of the medicine information seeking behaviour (MISB) of long term patients attending public health sector facilities; the development and validation of a medicine literacy test (MLT) to identify patients with limited health literacy requiring additional support and counselling; the development and evaluation of a patient-centred illustrated PIL for first-line TB treatment; the assessment of self-efficacy and adherence using modified versions of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and Morisky 8-item Medicine Adherence Scale (MMAS-8), respectively, and the investigation of the impact of the PIL on patient knowledge and these health-related behaviours. Six focus group discussions (FGDs) conducted in 34 isiXhosa-speaking patients with limited formal education taking long-term treatment explored themes related to information needs, information-seeking practices and awareness of and ability to utilize information sources. Codes were analysed and potential themes and subthemes were identified and refined. The findings of this study reflected a passive, disempowered patient due to both patient-related and systemic healthcare factors. Poor awareness of information sources, lack of health-related knowledge, stigma and lack of awareness of the importance of appropriate medicine-related knowledge contributed to a lack of information-seeking practice. Patients neither asked questions nor were encouraged to do so. All expressed an unmet need for information and a desire for receiving relevant, appropriate, written medicine-related information. Feedback from this phase of the study was used to inform the development of the targeted patientcentred PIL. A double-sided A4 PIL containing information about TB medicines was designed giving careful consideration to content, format and layout features. Twenty five pictograms were designed through a rigorous, iterative design process and were included in the PIL that was evaluated in a randomised control trial (RCT) conducted amongst 120 TB patients attending a high burden TB clinic in South Africa. Interviews were conducted in either isiXhosa or Afrikaans via a trained interpreter. Patients were randomly allocated to either a control (standard care) or an experimental group (standard care plus brief counselling using the PIL). Two interviews were conducted using a prepared questionnaire; one at baseline followed by a 4-week follow-up. Baseline data included demographics, medicine literacy test, health information sources, knowledge of TB medicines, self-reported adherence and self-efficacy. Data collected at the 4-week follow-up interview included TB knowledge, self-reported adherence, self-efficacy, opinion of TB medicine information and interpretation of pictograms. Data were analysed using t-test, correlations, chi-square and ANOVA tests at a 0.05 level of significance. The PIL was successful in improving patient knowledge of the disease, TB medicine-taking, side effects, drug-resistant TB and HIV and TB co-infection. At baseline, there was no significant difference in the overall mean percentage knowledge score between the control and experimental groups (p=0.074). At follow-up, the percentage knowledge score for the experimental group increased significantly from 59.0% to 84.6% (p<0.001) and showed a significantly higher score than the control group (p<0.001), displaying evidence of the impact of the PIL as a counselling tool on patient knowledge. The PIL generated a highly positive response in the experimental group who indicated that they had referred to the leaflet over the last month and that it had played an important role in improving their TB medicine-related knowledge. This was reflected in the experimental group knowledge score of greater than 80% for almost three quarters of the patients whereas only 14% in the control group achieved this score. Patients appreciated the inclusion of pictograms and strongly felt that they helped them to recall and understand the textual PIL content. The study found that patients want side effect information and, interestingly, did not perceive the presentation of side effects in pictorial form to constitute a risk factor for nonadherence. Use of the illustrated PIL (experimental group) resulted in a significant improvement in patient self-efficacy (p=0.002), but showed no effect on self-reported adherence (p=0.563). Neither self-efficacy nor adherence was influenced by gender, age or education. An education effect on knowledge was only observed in the control group at baseline. The newly developed MLT was shown to be a valid and reliable tool and a moderate, positive and significant correlation was noted between the MLT score and baseline TB medicine-related knowledge in both the control and experimental groups. As there is a paucity of studies investigating the influence of take-home written leaflets on TB medicine knowledge and on patient behaviour, this study represents a significant knowledge contribution. It is the first study to report the development and evaluation of a patient-centred PIL to address the dearth of available TB medicine information. The use of targeted user-friendly, illustrated information leaflets can be a valuable counselling aid to improve patient knowledge and self-efficacy, particularly among patients with limited literacy. However, careful consideration of the design and content, with input from the endusers at all stages of the process, will optimise its effectiveness. The proposed framework for the development and implementation of patient-centred health and medicines information in a developing country context presented in this thesis could be used as a theoretical basis for informing the development of effective information materials targeting other disease states. Local patients taking TB medicines identified nurses, WMI and media as their current sources of information but they expressed a strong desire to know more about their treatment. Targeted public health interventions that focus on medicine-taking information and behaviours and encourage patients to adopt a more active, questioning role in health consultations could improve health literacy and empower patients in their medicine-taking practices. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
- Authors: Patel, Sonal
- Date: 2015
- Subjects: Tuberculosis Patients , Health literacy , Patient education , Communication in medicine , Picture-writing
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194071 , vital:45420 , DOI 10.21504/10962/194071
- Description: South Africa carries a significant TB burden as evidenced in the 2013 statistics which report 450 000 new active TB cases and 890 000 TB-related mortalities. For successful treatment outcomes, 90% adherence is necessary, but many patients prematurely discontinue treatment due to poor knowledge and understanding of their complex TB medicines. Patient education is pivotal in improving knowledge, health literacy and behavioural outcomes such as health information seeking, self-efficacy and adherence. In the under-resourced South African healthcare system, time and capacity to adequately counsel patients are limited. The value of written medicine information (WMI) to supplement the verbal information provided by healthcare professionals (HCPs) has been widely investigated but minimal South African research is available. Current WMI distributed in South Africa is mainly generated by pharmaceutical manufacturers and is complex, incomprehensible and undesirable to patients. TB-related WMI focuses mainly on the disease, with little information relating to TB medicines and their use. The overall aim of this project was to improve patient knowledge about their TB medicines through the use of a simple illustrated patient information leaflet (PIL). Objectives to achieve this aim included: investigation of the medicine information seeking behaviour (MISB) of long term patients attending public health sector facilities; the development and validation of a medicine literacy test (MLT) to identify patients with limited health literacy requiring additional support and counselling; the development and evaluation of a patient-centred illustrated PIL for first-line TB treatment; the assessment of self-efficacy and adherence using modified versions of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and Morisky 8-item Medicine Adherence Scale (MMAS-8), respectively, and the investigation of the impact of the PIL on patient knowledge and these health-related behaviours. Six focus group discussions (FGDs) conducted in 34 isiXhosa-speaking patients with limited formal education taking long-term treatment explored themes related to information needs, information-seeking practices and awareness of and ability to utilize information sources. Codes were analysed and potential themes and subthemes were identified and refined. The findings of this study reflected a passive, disempowered patient due to both patient-related and systemic healthcare factors. Poor awareness of information sources, lack of health-related knowledge, stigma and lack of awareness of the importance of appropriate medicine-related knowledge contributed to a lack of information-seeking practice. Patients neither asked questions nor were encouraged to do so. All expressed an unmet need for information and a desire for receiving relevant, appropriate, written medicine-related information. Feedback from this phase of the study was used to inform the development of the targeted patientcentred PIL. A double-sided A4 PIL containing information about TB medicines was designed giving careful consideration to content, format and layout features. Twenty five pictograms were designed through a rigorous, iterative design process and were included in the PIL that was evaluated in a randomised control trial (RCT) conducted amongst 120 TB patients attending a high burden TB clinic in South Africa. Interviews were conducted in either isiXhosa or Afrikaans via a trained interpreter. Patients were randomly allocated to either a control (standard care) or an experimental group (standard care plus brief counselling using the PIL). Two interviews were conducted using a prepared questionnaire; one at baseline followed by a 4-week follow-up. Baseline data included demographics, medicine literacy test, health information sources, knowledge of TB medicines, self-reported adherence and self-efficacy. Data collected at the 4-week follow-up interview included TB knowledge, self-reported adherence, self-efficacy, opinion of TB medicine information and interpretation of pictograms. Data were analysed using t-test, correlations, chi-square and ANOVA tests at a 0.05 level of significance. The PIL was successful in improving patient knowledge of the disease, TB medicine-taking, side effects, drug-resistant TB and HIV and TB co-infection. At baseline, there was no significant difference in the overall mean percentage knowledge score between the control and experimental groups (p=0.074). At follow-up, the percentage knowledge score for the experimental group increased significantly from 59.0% to 84.6% (p<0.001) and showed a significantly higher score than the control group (p<0.001), displaying evidence of the impact of the PIL as a counselling tool on patient knowledge. The PIL generated a highly positive response in the experimental group who indicated that they had referred to the leaflet over the last month and that it had played an important role in improving their TB medicine-related knowledge. This was reflected in the experimental group knowledge score of greater than 80% for almost three quarters of the patients whereas only 14% in the control group achieved this score. Patients appreciated the inclusion of pictograms and strongly felt that they helped them to recall and understand the textual PIL content. The study found that patients want side effect information and, interestingly, did not perceive the presentation of side effects in pictorial form to constitute a risk factor for nonadherence. Use of the illustrated PIL (experimental group) resulted in a significant improvement in patient self-efficacy (p=0.002), but showed no effect on self-reported adherence (p=0.563). Neither self-efficacy nor adherence was influenced by gender, age or education. An education effect on knowledge was only observed in the control group at baseline. The newly developed MLT was shown to be a valid and reliable tool and a moderate, positive and significant correlation was noted between the MLT score and baseline TB medicine-related knowledge in both the control and experimental groups. As there is a paucity of studies investigating the influence of take-home written leaflets on TB medicine knowledge and on patient behaviour, this study represents a significant knowledge contribution. It is the first study to report the development and evaluation of a patient-centred PIL to address the dearth of available TB medicine information. The use of targeted user-friendly, illustrated information leaflets can be a valuable counselling aid to improve patient knowledge and self-efficacy, particularly among patients with limited literacy. However, careful consideration of the design and content, with input from the endusers at all stages of the process, will optimise its effectiveness. The proposed framework for the development and implementation of patient-centred health and medicines information in a developing country context presented in this thesis could be used as a theoretical basis for informing the development of effective information materials targeting other disease states. Local patients taking TB medicines identified nurses, WMI and media as their current sources of information but they expressed a strong desire to know more about their treatment. Targeted public health interventions that focus on medicine-taking information and behaviours and encourage patients to adopt a more active, questioning role in health consultations could improve health literacy and empower patients in their medicine-taking practices. , Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 2015
- Full Text:
The isolation, characterisation and chemotaxonomic significance of secondary metabolites from selected South African Laurencia spp. Rhodophyta
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
The quantification of fucoxanthin from selected South African marine brown algae (Phaeophyta) using HPLC-UV/Vis
- Authors: Mubaiwa, Byron Tawanda
- Date: 2015
- Subjects: Marine algae , Brown algae , High performance liquid chromatography , Functional foods , Xanthophylls , Carotenoids , Extraction (Chemistry)
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3868 , http://hdl.handle.net/10962/d1017879
- Description: Marine brown algae (seaweeds) are a rich source of fucoxanthin, a xanthophyll carotenoid that is naturally, an accessory pigment in the process of photosynthesis of sea vegetation such as Sargassum incisifolium. Fucoxanthin has been exploited by nutraceutical companies for its anti-obesity effects that has resulted in an increase of seaweed slimming preparations such as FucoThin™. The field is getting widespread consumer attention as interest in fucoxanthin has also transcended to its widespread biological potential which include cytotoxicity, anti-diabetic, anti-oxidant, anti-inflammatory and anti-plasmodium effects. We therefore wanted to identify a reliable source(s) of fucoxanthin from diverse samples of South African marine brown algae in order to explore our medicinal chemistry interests around the cytotoxicity and anti-malarial potential of fucoxanthin. A known source, Sargassum incisifolium, was used to isolate (maceration in CH₂Cl₂/MeOH at 35 °C followed by a hexane/EtOAc step gradient silica column of the crude extract and reversed phase semi-prep HPLC) and characterize (1D and 2D NMR) fucoxanthin (reference standard) in order to develop an analytical method for its determination in selected diverse brown algae commonly found in South Africa. The HPLC [Column: Phenomenex® Synergi™ (250 x 3.0 mm i.d); Mobile phase: ACN/H2O (95:5)] method developed for this analysis was validated according the guidelines set by the International Conference on Harmonization (ICH). Fifteen species were then assessed for fucoxanthin content (μg/g of dried weight) using the developed method. Stability studies on fucoxanthin were also carried out to assess photo- and pH degradation of fucoxanthin. Zonaria subarticulata (KOS130226-18) from Kenton-On-Sea beach and Sargassum incisifolium (PA130427-1) from Port Alfred beach were found to be the highest producers of fucoxanthin with 0.50 mg/g and 0.45 mg/g dried weight respectively. Fucoxanthin was found to be both photo-labile and sensitive to both acidic and basic pH environments. However, the pigment was more photostable in pure as opposed to extract form and also showed to be more stable at pH 10.0. Our findings show that Z. subarticulata and S. incisifolium could be reliable sources of fucoxanthin and can be considered as the algae to use in optimized extraction procedures in further studies. Also, when working with fucoxanthin, it is important to protect it from light. Any consideration of taking fucoxanthin preparation orally (as a nutraceutical) should consider protecting the active from the harsh conditions of the gastrointestinal tract. Any upscale production of fucoxanthin from seaweed should consider variations such as geographical, seasonal, lifecycle stage, etc. of identified algae as these may be important factors in obtaining effective concentrations of fucoxanthin.
- Full Text:
- Authors: Mubaiwa, Byron Tawanda
- Date: 2015
- Subjects: Marine algae , Brown algae , High performance liquid chromatography , Functional foods , Xanthophylls , Carotenoids , Extraction (Chemistry)
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3868 , http://hdl.handle.net/10962/d1017879
- Description: Marine brown algae (seaweeds) are a rich source of fucoxanthin, a xanthophyll carotenoid that is naturally, an accessory pigment in the process of photosynthesis of sea vegetation such as Sargassum incisifolium. Fucoxanthin has been exploited by nutraceutical companies for its anti-obesity effects that has resulted in an increase of seaweed slimming preparations such as FucoThin™. The field is getting widespread consumer attention as interest in fucoxanthin has also transcended to its widespread biological potential which include cytotoxicity, anti-diabetic, anti-oxidant, anti-inflammatory and anti-plasmodium effects. We therefore wanted to identify a reliable source(s) of fucoxanthin from diverse samples of South African marine brown algae in order to explore our medicinal chemistry interests around the cytotoxicity and anti-malarial potential of fucoxanthin. A known source, Sargassum incisifolium, was used to isolate (maceration in CH₂Cl₂/MeOH at 35 °C followed by a hexane/EtOAc step gradient silica column of the crude extract and reversed phase semi-prep HPLC) and characterize (1D and 2D NMR) fucoxanthin (reference standard) in order to develop an analytical method for its determination in selected diverse brown algae commonly found in South Africa. The HPLC [Column: Phenomenex® Synergi™ (250 x 3.0 mm i.d); Mobile phase: ACN/H2O (95:5)] method developed for this analysis was validated according the guidelines set by the International Conference on Harmonization (ICH). Fifteen species were then assessed for fucoxanthin content (μg/g of dried weight) using the developed method. Stability studies on fucoxanthin were also carried out to assess photo- and pH degradation of fucoxanthin. Zonaria subarticulata (KOS130226-18) from Kenton-On-Sea beach and Sargassum incisifolium (PA130427-1) from Port Alfred beach were found to be the highest producers of fucoxanthin with 0.50 mg/g and 0.45 mg/g dried weight respectively. Fucoxanthin was found to be both photo-labile and sensitive to both acidic and basic pH environments. However, the pigment was more photostable in pure as opposed to extract form and also showed to be more stable at pH 10.0. Our findings show that Z. subarticulata and S. incisifolium could be reliable sources of fucoxanthin and can be considered as the algae to use in optimized extraction procedures in further studies. Also, when working with fucoxanthin, it is important to protect it from light. Any consideration of taking fucoxanthin preparation orally (as a nutraceutical) should consider protecting the active from the harsh conditions of the gastrointestinal tract. Any upscale production of fucoxanthin from seaweed should consider variations such as geographical, seasonal, lifecycle stage, etc. of identified algae as these may be important factors in obtaining effective concentrations of fucoxanthin.
- Full Text:
Adherence to antiretroviral therapy in children in Zimbabwe: a randomized control trial to validate a new self-reported adherence monitoring tool
- Authors: Mugore, Linnetie
- Date: 2014
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54734 , vital:26607
- Description: Background: Among children taking antiretroviral therapy (ART), self-reports have been widely reported to over-estimate adherence levels. Pill count adherence levels are often lower than self-reported levels, with unannounced home pill count adherence being lower than facility based pill count adherence. There is often poor agreement between pill count adherence levels and those measured using other objective adherence measuring methods such as Medication Event Monitoring Systems (MEMS®), which is widely viewed as the gold standard for adherence measurement. Objectives: The aim of this study was to design and evaluate a new self-reported paediatric adherence monitoring tool, assess the feasibility of using pill count methods in monitoring adherence and identify challenges to reporting adherence among children on ART in rural and urban Zimbabwe. Methods A dual centre, superiority, parallel design RCT was conducted to evaluate the newly-developed visually- and verbally-cued „past 10 days‟ tool for the assessment of adherence in children on ART at two sites in Zimbabwe; Harare Central Children‟s Hospital in an urban setting, and Murambinda Mission Hospital, a rural site. Child-caregiver pairs presenting to one of these facilities for the child‟s review of ART and refill of the medication were recruited, signed informed consent obtained, and were randomised for self-reported adherence monitoring into either the experimental group („new 10-day tool‟) or the control group („PACTG-style‟ self-report tool). Data (demographic, socioeconomic, and reported adherence) were collected in individual interviews with child-caregiver pairs. Additional adherence monitoring methods used for both groups included the Morisky-8-Item Medication Adherence Scale (MMAS-8) and a facility based pill count. FGDs were held with groups of caregivers and groups of children ≥13 years of age to understand reasons for non-adherence as well as issues around reporting non-adherence. Superiority testing was conducted by comparing adherent proportions and their confidence intervals (95% CI). Further concurrent validity test was done using the Mann-Whitney U test to evaluate the relationship between the new tool and the MMAS-8 scores. Agreement between the child and caregiver reports of adherence was used as a test of reliability of the new tool using the kappa statistic. Socio-demographic, clinical and care-related factors associated with adherence were identified using reported adherence in both child and caregiver groups in a logistic regression model. Two pill count methods were assessed for feasibility using the proportions of children with complete data for calculating adherence levels, and their CI and a comparison of the two methods, a routinely-used method and one that incorporated the reported residual quantity (RRQ) of medication at last refill. Results : Analysis included 245 child-caregiver pairs, 123 in the experimental group and 122 in the control group. The median age for children was 9 years. In the experimental group, adherence by caregiver and child reports ranged from 94.3% - 98.4% and 78.4% - 96.1%, and those in the control group ranged from 89.2% - 97.5% and 71.2% - 98.1%, respectively. There was no significant difference between adherence levels in the two groups. Adherence levels measured by both the experimental and control tools were found to be associated with MMAS-8 adherence levels (p <0.05). Agreement between child- and caregiver-reported adherence was moderate though significant (kappa; 0.407, p <0.05). Only about half of the children had adequate data to compute pill counts. Proportions adherent at 95% cut-off were 39% by the „routine pill count‟ and 58% by the „Pill count RRQ‟. Being an orphan was associated with child reported-adherence whereas use of non-human reminders, having a maternal relative as a primary caregiver and knowledge of dose frequency, were all associated with caregiver-reported adherence. Major causes of non-adherence mentioned during the FGDs included interference of medication administration times with scheduling of routine socio-economic activities and lack of support from some non-biological caregivers. Reporting of non-adherence appeared to be hampered by perceptions of negative reactions by healthcare workers to these reports and by caregivers being unaware that the child missed some doses. Conclusions: The „new 10-day tool‟ was not shown to be superior to the „PACTG-style tool‟ in detecting non-adherence, however this new tool was found to be a valid and reliable adherence monitoring tool that included a moderately long recall period of 10 days, can be applied without the need for the respondent to remember names of individual medicines in the
- Full Text:
- Authors: Mugore, Linnetie
- Date: 2014
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54734 , vital:26607
- Description: Background: Among children taking antiretroviral therapy (ART), self-reports have been widely reported to over-estimate adherence levels. Pill count adherence levels are often lower than self-reported levels, with unannounced home pill count adherence being lower than facility based pill count adherence. There is often poor agreement between pill count adherence levels and those measured using other objective adherence measuring methods such as Medication Event Monitoring Systems (MEMS®), which is widely viewed as the gold standard for adherence measurement. Objectives: The aim of this study was to design and evaluate a new self-reported paediatric adherence monitoring tool, assess the feasibility of using pill count methods in monitoring adherence and identify challenges to reporting adherence among children on ART in rural and urban Zimbabwe. Methods A dual centre, superiority, parallel design RCT was conducted to evaluate the newly-developed visually- and verbally-cued „past 10 days‟ tool for the assessment of adherence in children on ART at two sites in Zimbabwe; Harare Central Children‟s Hospital in an urban setting, and Murambinda Mission Hospital, a rural site. Child-caregiver pairs presenting to one of these facilities for the child‟s review of ART and refill of the medication were recruited, signed informed consent obtained, and were randomised for self-reported adherence monitoring into either the experimental group („new 10-day tool‟) or the control group („PACTG-style‟ self-report tool). Data (demographic, socioeconomic, and reported adherence) were collected in individual interviews with child-caregiver pairs. Additional adherence monitoring methods used for both groups included the Morisky-8-Item Medication Adherence Scale (MMAS-8) and a facility based pill count. FGDs were held with groups of caregivers and groups of children ≥13 years of age to understand reasons for non-adherence as well as issues around reporting non-adherence. Superiority testing was conducted by comparing adherent proportions and their confidence intervals (95% CI). Further concurrent validity test was done using the Mann-Whitney U test to evaluate the relationship between the new tool and the MMAS-8 scores. Agreement between the child and caregiver reports of adherence was used as a test of reliability of the new tool using the kappa statistic. Socio-demographic, clinical and care-related factors associated with adherence were identified using reported adherence in both child and caregiver groups in a logistic regression model. Two pill count methods were assessed for feasibility using the proportions of children with complete data for calculating adherence levels, and their CI and a comparison of the two methods, a routinely-used method and one that incorporated the reported residual quantity (RRQ) of medication at last refill. Results : Analysis included 245 child-caregiver pairs, 123 in the experimental group and 122 in the control group. The median age for children was 9 years. In the experimental group, adherence by caregiver and child reports ranged from 94.3% - 98.4% and 78.4% - 96.1%, and those in the control group ranged from 89.2% - 97.5% and 71.2% - 98.1%, respectively. There was no significant difference between adherence levels in the two groups. Adherence levels measured by both the experimental and control tools were found to be associated with MMAS-8 adherence levels (p <0.05). Agreement between child- and caregiver-reported adherence was moderate though significant (kappa; 0.407, p <0.05). Only about half of the children had adequate data to compute pill counts. Proportions adherent at 95% cut-off were 39% by the „routine pill count‟ and 58% by the „Pill count RRQ‟. Being an orphan was associated with child reported-adherence whereas use of non-human reminders, having a maternal relative as a primary caregiver and knowledge of dose frequency, were all associated with caregiver-reported adherence. Major causes of non-adherence mentioned during the FGDs included interference of medication administration times with scheduling of routine socio-economic activities and lack of support from some non-biological caregivers. Reporting of non-adherence appeared to be hampered by perceptions of negative reactions by healthcare workers to these reports and by caregivers being unaware that the child missed some doses. Conclusions: The „new 10-day tool‟ was not shown to be superior to the „PACTG-style tool‟ in detecting non-adherence, however this new tool was found to be a valid and reliable adherence monitoring tool that included a moderately long recall period of 10 days, can be applied without the need for the respondent to remember names of individual medicines in the
- Full Text:
Adolescent pregnancy: a community engaged participatory approach to design and implement an educational intervention
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
An investigation of the potential anti-diabetic (insulinomimetic) activity of anti-oxidant compounds derived from Sargassum heterophyllum
- Authors: Nyambe, Mutenta Nsokolo
- Date: 2014
- Subjects: Sargassum , Diabetes -- Chemotherapy , Diabetes -- Africa , Antioxidants -- Therapeutic use , Marine algae , Endemic plants -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3874 , http://hdl.handle.net/10962/d1021020
- Description: In Africa, non-communicable diseases such as diabetes mellitus have been generally neglected. This problem has worsened over the years owing to continuous threats from infectious diseases such as HIV/AIDS, tuberculosis and malaria. Despite this, statistics have shown that by 2030, the African region will have the highest proportional increase in diabetes prevalence. Over 80% of all diabetic deaths occur in developing countries probably not only due to poor equity of access to medication but also due to limited efficacy and side effects associated with the commonly available anti-diabetic agents. Therefore, this creates the desperate need for the development of new anti-diabetic agents that are more efficacious and can be sourced from within the continent. With oxidative stress as a suggested mechanism underlying the cause of diabetes mellitus and diabetic complications, the discovery of natural anti-oxidants that prevent free radical mediated damage is important for developing new treatment strategies. Marine algae have been identified as good sources for natural anti-oxidants. Unfortunately, very few studies have embarked on the discovery of marine-derived anti-oxidant compounds with potential anti-diabetic activity. In this project, we investigated the potential anti-oxidant activity of the South African endemic algae Stypopodium multipartitum, Dictyopterus ligulata, Cystophora fibriosa, Bifurcariopsis capensis, Sargassum sp. and Sargassum heterophyllum. From these studies, Sargassum heterophyllum yielded prenylated compounds, the main compound being sargahydroquinoic acid (3.6) and the carotenoid metabolite fucoxanthin (3.8), which are in part responsible for the radical scavenging activity of the crude extract. Sargahydroquinoic acid (3.6) and fucoxanthin (3.8) also exhibited significant anti-inflammatory activity. Sargaquinoic acid (3.1), sargachromenoic acid (3.9) and sarganaphthoquinoic acid (3.10) were then semi-synthesized from sargahydroquinoic acid (3.6) and their in-vitro cytotoxicity profiles evaluated using Chang Liver, HT-29, Caco-2 and 3T3-L1 cell lines prior to antidiabetic testing. From the semi-synthetic derivatives, sargachromenoic acid (3.9) exhibited the most potent anti-oxidant activity (IC₅₀ = 6.99 μg/mL). After the evaluation of antidiabetic activity using 3T3-L1 preadipocyte differentiation, sarganaphthoquinoic acid (3.10) showed the most potent insulinomimetic activity at 1.19 μM by inducing a PPARγ response similar to that of rosiglitazone at 1 μM.
- Full Text:
- Authors: Nyambe, Mutenta Nsokolo
- Date: 2014
- Subjects: Sargassum , Diabetes -- Chemotherapy , Diabetes -- Africa , Antioxidants -- Therapeutic use , Marine algae , Endemic plants -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3874 , http://hdl.handle.net/10962/d1021020
- Description: In Africa, non-communicable diseases such as diabetes mellitus have been generally neglected. This problem has worsened over the years owing to continuous threats from infectious diseases such as HIV/AIDS, tuberculosis and malaria. Despite this, statistics have shown that by 2030, the African region will have the highest proportional increase in diabetes prevalence. Over 80% of all diabetic deaths occur in developing countries probably not only due to poor equity of access to medication but also due to limited efficacy and side effects associated with the commonly available anti-diabetic agents. Therefore, this creates the desperate need for the development of new anti-diabetic agents that are more efficacious and can be sourced from within the continent. With oxidative stress as a suggested mechanism underlying the cause of diabetes mellitus and diabetic complications, the discovery of natural anti-oxidants that prevent free radical mediated damage is important for developing new treatment strategies. Marine algae have been identified as good sources for natural anti-oxidants. Unfortunately, very few studies have embarked on the discovery of marine-derived anti-oxidant compounds with potential anti-diabetic activity. In this project, we investigated the potential anti-oxidant activity of the South African endemic algae Stypopodium multipartitum, Dictyopterus ligulata, Cystophora fibriosa, Bifurcariopsis capensis, Sargassum sp. and Sargassum heterophyllum. From these studies, Sargassum heterophyllum yielded prenylated compounds, the main compound being sargahydroquinoic acid (3.6) and the carotenoid metabolite fucoxanthin (3.8), which are in part responsible for the radical scavenging activity of the crude extract. Sargahydroquinoic acid (3.6) and fucoxanthin (3.8) also exhibited significant anti-inflammatory activity. Sargaquinoic acid (3.1), sargachromenoic acid (3.9) and sarganaphthoquinoic acid (3.10) were then semi-synthesized from sargahydroquinoic acid (3.6) and their in-vitro cytotoxicity profiles evaluated using Chang Liver, HT-29, Caco-2 and 3T3-L1 cell lines prior to antidiabetic testing. From the semi-synthetic derivatives, sargachromenoic acid (3.9) exhibited the most potent anti-oxidant activity (IC₅₀ = 6.99 μg/mL). After the evaluation of antidiabetic activity using 3T3-L1 preadipocyte differentiation, sarganaphthoquinoic acid (3.10) showed the most potent insulinomimetic activity at 1.19 μM by inducing a PPARγ response similar to that of rosiglitazone at 1 μM.
- Full Text:
Development and assessment of sustained release stavudine loaded microparticles
- Authors: Zindove, Chiedza Cathrine
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54722 , vital:26603
- Description:
Stavudine (D4T) has been used as first line treatment for HIV/AIDS and is part of highly active anti retroviral treatment (HAART). It is an affordable medicine and its use is beneficial in resource limited settings. However D4T exhibits dose dependent side effects that may lead to non-adherence in patients. This study was undertaken to formulate, develop and manufacture a dosage form that could reduce dose dependent side effects by decreasing the dose of D4T but still exhibit antiretroviral (ARV) activity. The use of sustained release (SR) formulations of D4T that ensure constant levels of the D4T in the body would not only optimize therapy but also reduce the incidence of side effects thereby increasing patient adherence. SR microparticles containing 30mg D4T were manufactured and loaded into size 3 hard gelatine capsules prior to analysis. The D4T microparticles were manufactured by microencapsulation using non-aqueous oil-in-oil solvent evaporation approach. D4T-excipient, excipient-excipient interactions and D4T purity were assessed using Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Copolymers synthesized from acrylic and methacrylic acid esters viz., Eudragit® RSPO and S100 were used as rate retardant materials and the effect of microcrystalline cellulose (Avicel® PH102) on the microparticles was also investigated. Magnesium stearate was used as a droplet stabilizer and n-hexane was added to harden the microspheres formed in a liquid paraffin continuous phase. The microparticles were optimized using a Box Behnken design and Response Surface Methodology (RSM). The microparticles were characterized in terms of their flow properties and encapsulation efficiency (% EE), in addition to visualization of the surface morphology with Scanning Electron Microscopy. In vitro D4T release studies were performed using USP Apparatus III in media of different pH and the samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection that had been developed and optimized using a Central Composite Design (CCD). The method was validated according to ICH guidelines. The IR spectra and DSC thermographs revealed that D4T exhibited thermal stability and there was no evidence of D4T-excipient and excipient-excipient interactions. The microparticles that were produced were white, free flowing and were obtained in a high yield with high encapsulation efficiency. Scanning Electron Microscopy studies revealed that the microparticles were spherical and porous in nature. In vitro D4T release extended to 12 hours and the mechanism of release was established using model dependent methods by fitting the data to a Zero order, First order, Higuchi and Hixson Crowell model. It was observed that the mechanism of D4T release was diffusion-controlled and that the data was best fitted to the Higuchi model with correlation coefficients > 0.9. The release mechanism was confirmed using the Korsmeyer-Peppas model that revealed that most of the formulations exhibited anomalous transport kinetics with the release exponent, n, ranging from 0.5
- Full Text:
- Authors: Zindove, Chiedza Cathrine
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54722 , vital:26603
- Description:
Stavudine (D4T) has been used as first line treatment for HIV/AIDS and is part of highly active anti retroviral treatment (HAART). It is an affordable medicine and its use is beneficial in resource limited settings. However D4T exhibits dose dependent side effects that may lead to non-adherence in patients. This study was undertaken to formulate, develop and manufacture a dosage form that could reduce dose dependent side effects by decreasing the dose of D4T but still exhibit antiretroviral (ARV) activity. The use of sustained release (SR) formulations of D4T that ensure constant levels of the D4T in the body would not only optimize therapy but also reduce the incidence of side effects thereby increasing patient adherence. SR microparticles containing 30mg D4T were manufactured and loaded into size 3 hard gelatine capsules prior to analysis. The D4T microparticles were manufactured by microencapsulation using non-aqueous oil-in-oil solvent evaporation approach. D4T-excipient, excipient-excipient interactions and D4T purity were assessed using Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Copolymers synthesized from acrylic and methacrylic acid esters viz., Eudragit® RSPO and S100 were used as rate retardant materials and the effect of microcrystalline cellulose (Avicel® PH102) on the microparticles was also investigated. Magnesium stearate was used as a droplet stabilizer and n-hexane was added to harden the microspheres formed in a liquid paraffin continuous phase. The microparticles were optimized using a Box Behnken design and Response Surface Methodology (RSM). The microparticles were characterized in terms of their flow properties and encapsulation efficiency (% EE), in addition to visualization of the surface morphology with Scanning Electron Microscopy. In vitro D4T release studies were performed using USP Apparatus III in media of different pH and the samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection that had been developed and optimized using a Central Composite Design (CCD). The method was validated according to ICH guidelines. The IR spectra and DSC thermographs revealed that D4T exhibited thermal stability and there was no evidence of D4T-excipient and excipient-excipient interactions. The microparticles that were produced were white, free flowing and were obtained in a high yield with high encapsulation efficiency. Scanning Electron Microscopy studies revealed that the microparticles were spherical and porous in nature. In vitro D4T release extended to 12 hours and the mechanism of release was established using model dependent methods by fitting the data to a Zero order, First order, Higuchi and Hixson Crowell model. It was observed that the mechanism of D4T release was diffusion-controlled and that the data was best fitted to the Higuchi model with correlation coefficients > 0.9. The release mechanism was confirmed using the Korsmeyer-Peppas model that revealed that most of the formulations exhibited anomalous transport kinetics with the release exponent, n, ranging from 0.5
- Full Text:
Establishing a formulation design space for a generic clobetasol 17- propionate cream using the principles of quality by design
- Fauzee, Ayeshah Fateemah Beebee
- Authors: Fauzee, Ayeshah Fateemah Beebee
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:20983 , http://hdl.handle.net/10962/5868
- Description: The pharmaceutical industry is global, is highly regulated and is able to achieve reasonable product quality but at high cost with maximum effort. Numerous challenges face the pharmaceutical industry and include a shrinking research pipeline, less innovation, outsourcing, investments, increasing research and development costs, long approval times, growth of the generic industry, failure to understand or analyze manufacturing failure and wastage as high at fifty percent for some pharmaceutical products. An efficient and flexible pharmaceutical sector should be able to consistently produce high quality pharmaceutical products at a reduced cost with minimal waste. As a result, Food and Drug Administration (FDA) and other agencies such as the International Conference on Harmonization (ICH) have embraced a “Quality by Design” (QbD) paradigm and this has become the “desired state” so as to shift manufacturing from being empirical to a science, engineering, and risk based approach. QbD is a systematic approach for the development of high quality pharmaceutical dosage forms that begins with predefined objectives based on the premise that quality must be built into and not tested into a product. QbD together with the establishment of a design space for dosage forms is a fairly new concept and there is limited published data on QbD concepts that report the entire process of identifying Critical Quality Attributes (CQA), design of a formulation and manufacturing process to meet product CQA, understanding the impact of material attributes and process parameters on product CQA, identification and controlling sources of variability in materials and processes that affect the CQA of a product and finally establishing, evaluating and testing a design space using both in vitro and in vivo approaches to assure that a product of consistent quality can always be produced. The objective of these studies was to implement a QbD approach to establish a design space for the development and manufacture of a safe, effective, stable generic formulation containing 0.05% w/w clobetasol 17-propionate (CP) that had similar in vitro and in vivo characteristics to an innovator product, Dermovate® (Sekpharma® Pty Ltd, Sandton, Gauteng, RSA). Such a product would pose a minimal risk of failure when treating severe skin disorders such as seborrhoeic dermatitis, extreme photodermatitis and/or severe psoriasis in HIV/AIDS patients in Southern Africa.
- Full Text:
- Authors: Fauzee, Ayeshah Fateemah Beebee
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:20983 , http://hdl.handle.net/10962/5868
- Description: The pharmaceutical industry is global, is highly regulated and is able to achieve reasonable product quality but at high cost with maximum effort. Numerous challenges face the pharmaceutical industry and include a shrinking research pipeline, less innovation, outsourcing, investments, increasing research and development costs, long approval times, growth of the generic industry, failure to understand or analyze manufacturing failure and wastage as high at fifty percent for some pharmaceutical products. An efficient and flexible pharmaceutical sector should be able to consistently produce high quality pharmaceutical products at a reduced cost with minimal waste. As a result, Food and Drug Administration (FDA) and other agencies such as the International Conference on Harmonization (ICH) have embraced a “Quality by Design” (QbD) paradigm and this has become the “desired state” so as to shift manufacturing from being empirical to a science, engineering, and risk based approach. QbD is a systematic approach for the development of high quality pharmaceutical dosage forms that begins with predefined objectives based on the premise that quality must be built into and not tested into a product. QbD together with the establishment of a design space for dosage forms is a fairly new concept and there is limited published data on QbD concepts that report the entire process of identifying Critical Quality Attributes (CQA), design of a formulation and manufacturing process to meet product CQA, understanding the impact of material attributes and process parameters on product CQA, identification and controlling sources of variability in materials and processes that affect the CQA of a product and finally establishing, evaluating and testing a design space using both in vitro and in vivo approaches to assure that a product of consistent quality can always be produced. The objective of these studies was to implement a QbD approach to establish a design space for the development and manufacture of a safe, effective, stable generic formulation containing 0.05% w/w clobetasol 17-propionate (CP) that had similar in vitro and in vivo characteristics to an innovator product, Dermovate® (Sekpharma® Pty Ltd, Sandton, Gauteng, RSA). Such a product would pose a minimal risk of failure when treating severe skin disorders such as seborrhoeic dermatitis, extreme photodermatitis and/or severe psoriasis in HIV/AIDS patients in Southern Africa.
- Full Text:
Formulation, development and assessment of efavirenz-loaded lipid nanocarriers
- Authors: Makoni, Pedzisai Anotida
- Date: 2014
- Subjects: Nanomedicine , Drug delivery systems , Antiretroviral agents Psychotropic effects , AIDS dementia complex
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/209981 , vital:47448
- Description: The feasibility of incorporating efavirenz (EFV) into innovative solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using the hot high-pressure homogenization (HHPH) technique was investigated in an attempt to address the shortcomings in therapy associated with the use of conventional dosage forms. The shortcomings include the unpalatable taste of API in solution, instability in the presence of light when in solution and psychiatric side effects of the API. In particular, sustained release approaches may reduce or limit the incidence of adverse psychiatric effects of EFV and alleviate Acquired Immune Deficiency Syndrome (AIDS)-related complications such as AIDS Dementia Complex (ADC) in patients, ultimately improving their quality of life. Prior to initiating pre-formulation, formulation development and optimization studies of EFV-loaded SLN and/or NLC, Response Surface Methodology (RSM) in conjunction with central composite design (CCD), was used to develop and validate suitable methods for the quantitative determination of EFV in pharmaceutical formulations and for monitoring EFV release from SLN and/or NLC in vitro. Simple, accurate, precise, sensitive and stabilityindicating reversed phase-high performance liquid chromatography (RP-HPLC) methods with UV and electrochemical (EC) detection were developed, validated and optimized for in vitro analysis of EFV in formulations. On the basis of risk-to-benefit ratio the RP-HPLC method with UV detection was selected as the most suitable for the quantitative determination of EFV in pharmaceutical formulations, and was applied to in vitro release studies of EFV from SLN and/or NLC. Pre-formulation studies were undertaken to investigate the thermal stability of EFV so as to facilitate the selection of lipid excipients for the manufacture of nanocarriers, and to establish their compatibility with EFV. It was found that EFV was thermostable up to a temperature of approximately 200°C, indicating that HHPH could be used for the manufacture of EFV-loaded SLN and/or NLC. Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate and Transcutol® HP showing the best solubilizing potential for EFV. Glyceryl monostearate exists in a stable β-modification prior to exposure to heat, but exists in the α-polymorphic modification following exposure to heat. It was established that the addition of Transcutol® HP to glyceryl monostearate revealed the co-existence of the α- and β’-polymorphic modifications, thereby revealing the existence of the modifications in NLC produced from the optimum lipid combination. Furthermore, an investigation of binary mixtures of EFV/glyceryl monostearate and glyceryl monostearate/Transcutol® HP, in addition to eutectic mixtures of EFV, glyceryl monostearate and Transcutol® HP, revealed no interaction between EFV and the lipids selected for the production of the nanocarriers. Due to the significantly higher solubility of EFV in Transcutol® HP than in to glyceryl monostearate, NLC are most likely to have a higher LC and EE than SLN. In addition, the existence of both the α- and β’-polymorphic modifications in the binary mixture of the lipid implies that EFV expulsion on prolonged storage is unlikely to occur from NLC when compared to SLN. Consequently formulation development and optimization studies of SLN and NLC were performed to investigate the potential to deliver EFV from a novel technology with an appropriate LC and EE for EFV. Tween®80 was selected for use in these formulations as the use of this surfactant facilitates the targeting of nanocarriers to the CNS. RSM in conjunction with a Box-Behnken Design (BBD) was used to establish the effects of process variables, such as number of homogenization cycles and pressure, in addition to formulation variables such as amount of EFV and Tween®80 on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), visual assessment (VA) and release rate (RR) of EFV after 24 hours. In addition the LC and EE, degree of crystallinity and lipid modification, shape and surface morphology of the optimized batches were investigated to ensure that EFV-loaded SLN and NLC of desirable quality were produced. On the day of manufacture the mean PS and PDI of EFV-loaded SLN was 59.00 ± 23.16 nm and 0.382 ± 0.054 respectively. The mean PS and PDI of EFV-loaded NLC was 34.73 ± 0.7709 nm and 0.394 ± 0.027 respectively. The formulations were in the nanometer range and exhibited a narrow particle size distribution, as indicated by the PDI values. The ZP values for optimized SLN and NLC generated on the day of manufacture using HPLC grade water as the dispersion medium were -32.5 ± 4.99 mV and -22.4 ± 3.72 mV respectively. In addition the optimized batches of SLN and NLC revealed a decrease in crystallinity in comparison to bulk lipid material. DSC, WAXS and FT-IR revealed that EFV was molecularly dispersed in the nanocarriers. In addition EFV-loaded SLN existed in a single α-polymorphic form, whereas EFV-loaded NLC exhibited the co-existence of α- and β’-polymorphic forms. Generally SLN and NLC were spherically shaped when viewed under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). On the day of manufacture the EE and LC of EFVloaded SLN was found to be 96.77 ± 0.453 % and 9.68 ± 1.772 % respectively. The EE and LC of EFV-loaded NLC was 99.93 ± 0.413 and 9.995 ± 0.672 respectively. The release profiles for the optimized formulations of SLN and NLC exhibited an initial burst release over the first 0-3 hours of testing, after which the release was sustained for up to 24 hours. The cumulative % EFV released over 24 hours was higher from SLN (91.5±3.423 %) than that observed for NLC (73.6±4.34 %). Stability studies performed for 8 weeks on the optimized batches of the SLN and the NLC were also conducted so as to ensure product quality. The formulations were assessed in terms of parameters considered benchmarks of stability, and included ZP, PS, PDI, LC and EE. Generally these parameters remained unchanged following storage for 8 weeks at 25°C/60% RH but showed considerable changes following storage for 8 weeks at 40°C/75% RH. These studies reveal that SLN and NLC when stored at 25°C/60% RH have the potential to be used as colloidal delivery systems for EFV that have the potential to protect EFV from photodegradation and sustain release into brain tissue. The latter will ultimately reduce or limit the incidence of adverse psychiatric effects and potentially alleviate AIDS-related complications such as ADC in patients with HIV/AIDS, ultimately improving their quality of life. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2014
- Full Text:
- Authors: Makoni, Pedzisai Anotida
- Date: 2014
- Subjects: Nanomedicine , Drug delivery systems , Antiretroviral agents Psychotropic effects , AIDS dementia complex
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/209981 , vital:47448
- Description: The feasibility of incorporating efavirenz (EFV) into innovative solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using the hot high-pressure homogenization (HHPH) technique was investigated in an attempt to address the shortcomings in therapy associated with the use of conventional dosage forms. The shortcomings include the unpalatable taste of API in solution, instability in the presence of light when in solution and psychiatric side effects of the API. In particular, sustained release approaches may reduce or limit the incidence of adverse psychiatric effects of EFV and alleviate Acquired Immune Deficiency Syndrome (AIDS)-related complications such as AIDS Dementia Complex (ADC) in patients, ultimately improving their quality of life. Prior to initiating pre-formulation, formulation development and optimization studies of EFV-loaded SLN and/or NLC, Response Surface Methodology (RSM) in conjunction with central composite design (CCD), was used to develop and validate suitable methods for the quantitative determination of EFV in pharmaceutical formulations and for monitoring EFV release from SLN and/or NLC in vitro. Simple, accurate, precise, sensitive and stabilityindicating reversed phase-high performance liquid chromatography (RP-HPLC) methods with UV and electrochemical (EC) detection were developed, validated and optimized for in vitro analysis of EFV in formulations. On the basis of risk-to-benefit ratio the RP-HPLC method with UV detection was selected as the most suitable for the quantitative determination of EFV in pharmaceutical formulations, and was applied to in vitro release studies of EFV from SLN and/or NLC. Pre-formulation studies were undertaken to investigate the thermal stability of EFV so as to facilitate the selection of lipid excipients for the manufacture of nanocarriers, and to establish their compatibility with EFV. It was found that EFV was thermostable up to a temperature of approximately 200°C, indicating that HHPH could be used for the manufacture of EFV-loaded SLN and/or NLC. Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate and Transcutol® HP showing the best solubilizing potential for EFV. Glyceryl monostearate exists in a stable β-modification prior to exposure to heat, but exists in the α-polymorphic modification following exposure to heat. It was established that the addition of Transcutol® HP to glyceryl monostearate revealed the co-existence of the α- and β’-polymorphic modifications, thereby revealing the existence of the modifications in NLC produced from the optimum lipid combination. Furthermore, an investigation of binary mixtures of EFV/glyceryl monostearate and glyceryl monostearate/Transcutol® HP, in addition to eutectic mixtures of EFV, glyceryl monostearate and Transcutol® HP, revealed no interaction between EFV and the lipids selected for the production of the nanocarriers. Due to the significantly higher solubility of EFV in Transcutol® HP than in to glyceryl monostearate, NLC are most likely to have a higher LC and EE than SLN. In addition, the existence of both the α- and β’-polymorphic modifications in the binary mixture of the lipid implies that EFV expulsion on prolonged storage is unlikely to occur from NLC when compared to SLN. Consequently formulation development and optimization studies of SLN and NLC were performed to investigate the potential to deliver EFV from a novel technology with an appropriate LC and EE for EFV. Tween®80 was selected for use in these formulations as the use of this surfactant facilitates the targeting of nanocarriers to the CNS. RSM in conjunction with a Box-Behnken Design (BBD) was used to establish the effects of process variables, such as number of homogenization cycles and pressure, in addition to formulation variables such as amount of EFV and Tween®80 on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), visual assessment (VA) and release rate (RR) of EFV after 24 hours. In addition the LC and EE, degree of crystallinity and lipid modification, shape and surface morphology of the optimized batches were investigated to ensure that EFV-loaded SLN and NLC of desirable quality were produced. On the day of manufacture the mean PS and PDI of EFV-loaded SLN was 59.00 ± 23.16 nm and 0.382 ± 0.054 respectively. The mean PS and PDI of EFV-loaded NLC was 34.73 ± 0.7709 nm and 0.394 ± 0.027 respectively. The formulations were in the nanometer range and exhibited a narrow particle size distribution, as indicated by the PDI values. The ZP values for optimized SLN and NLC generated on the day of manufacture using HPLC grade water as the dispersion medium were -32.5 ± 4.99 mV and -22.4 ± 3.72 mV respectively. In addition the optimized batches of SLN and NLC revealed a decrease in crystallinity in comparison to bulk lipid material. DSC, WAXS and FT-IR revealed that EFV was molecularly dispersed in the nanocarriers. In addition EFV-loaded SLN existed in a single α-polymorphic form, whereas EFV-loaded NLC exhibited the co-existence of α- and β’-polymorphic forms. Generally SLN and NLC were spherically shaped when viewed under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). On the day of manufacture the EE and LC of EFVloaded SLN was found to be 96.77 ± 0.453 % and 9.68 ± 1.772 % respectively. The EE and LC of EFV-loaded NLC was 99.93 ± 0.413 and 9.995 ± 0.672 respectively. The release profiles for the optimized formulations of SLN and NLC exhibited an initial burst release over the first 0-3 hours of testing, after which the release was sustained for up to 24 hours. The cumulative % EFV released over 24 hours was higher from SLN (91.5±3.423 %) than that observed for NLC (73.6±4.34 %). Stability studies performed for 8 weeks on the optimized batches of the SLN and the NLC were also conducted so as to ensure product quality. The formulations were assessed in terms of parameters considered benchmarks of stability, and included ZP, PS, PDI, LC and EE. Generally these parameters remained unchanged following storage for 8 weeks at 25°C/60% RH but showed considerable changes following storage for 8 weeks at 40°C/75% RH. These studies reveal that SLN and NLC when stored at 25°C/60% RH have the potential to be used as colloidal delivery systems for EFV that have the potential to protect EFV from photodegradation and sustain release into brain tissue. The latter will ultimately reduce or limit the incidence of adverse psychiatric effects and potentially alleviate AIDS-related complications such as ADC in patients with HIV/AIDS, ultimately improving their quality of life. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2014
- Full Text:
Synthesis and structure-activity relationship studies of 1,4-naphthoquinone derivatives as potential anti-trypanosomal agents
- Authors: Chakaingesu, Chikomborero
- Date: 2014
- Subjects: African trypanosomiasis , Trypanosoma brucei , Naphthoquinone , Protozoan diseases , Drugs -- Structure-activity relationships , Millennium Development Goals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3873 , http://hdl.handle.net/10962/d1020959
- Description: Human African Trypanosomiasis (HAT) is an infectious, vector-borne protozoal disease which is amongst the so-called neglected diseases. In 2000, at a summit of the United Nations, eight Millennium Development Goals (MDGs) were set, to be achieved by 2015. MDG 6 states “to combat HIV/AIDS, malaria & other diseases”. With just under 2 years to go before the end of 2015, HAT is still thriving in developing countries. The drugs currently used for the treatment of HAT are in short supply, have severe side effects and those used to treat late stages of the disease are very difficult to administer. The aforementioned challenges call for research into this neglected disease in order to develop new, safe and easy-to-use medicines. Naphthoquinones are a class of compounds shown to possess anti-parasitic activity, amongst a variety of other biological activities, and therefore this pharmacophore was selected for this study. The purpose of this study was to synthesise derivatives of 2,3-dichloro-1,4- naphthoquinone to be tested for anti-trypanosomal activity and thereafter conduct structureactivity relationship studies. A series of reactions were carried out using thiophenol, phenol and aniline nucleophiles to synthesise thioether (-S-), ether (-O-) and amino (-NH-) derivatives of 2,3-dichloro-1,4-naphthoquinone with various halogen or methyl substituents. Purification of the products was carried out by recrystallisation. Nuclear magnetic resonance (NMR), infra-red (IR) and high pressure liquid chromatography coupled to an electro-spray ionisation mass spectrometer (HPLC-ESI-MS) were the analytical methods used for structural confirmation of the products. There were eighteen 1,4-naphthoquinone derivatives that were successfully synthesised using ethanolic solutions. Unfortunately, attempts to synthesise 1,4-naphthoquinones in reactions involving 2-(trifluoro-methyl)aniline and 2-isopropyl-5-methylphenol were unsuccessful, presumably due to steric hindrance by the bulky ortho-substituents. Although the aims of the synthetic procedures were to obtain both mono- and disubstituted products by nucleophilic displacement of the chlorine atom(s) of 2,3-dichloro-1,4- naphthoquinone, only monosubstituted products were obtained from substitution with aniline and phenol nucleophiles. Thiol nucleophiles, however, selectively yielded disubstituted products only. Synthesised naphthoquinone derivatives were tested against Trypanosoma brucei and calculation of the EC₅₀ values from the obtained dose-response curves was carried out using the four parametric equation. All the 1,4-naphthoquinones showed a degree of potency, except compounds 1b, 3c and 3e, which had little or lack of potency. Structure-activity relationship studies (SARs and QSARs) were carried out to determine which structural features or functional group substituents of the naphthoquinone derivatives contribute or take away from the desired anti-trypanosomal activity. It was found that compounds with the best in vitro anti-trypanosomal potencies in the series of analogous 1,4-naphthoquinone derivatives had EC₅₀ values in the range 2.137 to 2.884 μM. The most potent compound in the series was 2-chloro-3-(4-(trifluoromethyl)phenylamino)-1,4- naphthoquinone 1e; but it was 142-fold less potent than the reference standard of melarsoprol.
- Full Text:
- Authors: Chakaingesu, Chikomborero
- Date: 2014
- Subjects: African trypanosomiasis , Trypanosoma brucei , Naphthoquinone , Protozoan diseases , Drugs -- Structure-activity relationships , Millennium Development Goals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3873 , http://hdl.handle.net/10962/d1020959
- Description: Human African Trypanosomiasis (HAT) is an infectious, vector-borne protozoal disease which is amongst the so-called neglected diseases. In 2000, at a summit of the United Nations, eight Millennium Development Goals (MDGs) were set, to be achieved by 2015. MDG 6 states “to combat HIV/AIDS, malaria & other diseases”. With just under 2 years to go before the end of 2015, HAT is still thriving in developing countries. The drugs currently used for the treatment of HAT are in short supply, have severe side effects and those used to treat late stages of the disease are very difficult to administer. The aforementioned challenges call for research into this neglected disease in order to develop new, safe and easy-to-use medicines. Naphthoquinones are a class of compounds shown to possess anti-parasitic activity, amongst a variety of other biological activities, and therefore this pharmacophore was selected for this study. The purpose of this study was to synthesise derivatives of 2,3-dichloro-1,4- naphthoquinone to be tested for anti-trypanosomal activity and thereafter conduct structureactivity relationship studies. A series of reactions were carried out using thiophenol, phenol and aniline nucleophiles to synthesise thioether (-S-), ether (-O-) and amino (-NH-) derivatives of 2,3-dichloro-1,4-naphthoquinone with various halogen or methyl substituents. Purification of the products was carried out by recrystallisation. Nuclear magnetic resonance (NMR), infra-red (IR) and high pressure liquid chromatography coupled to an electro-spray ionisation mass spectrometer (HPLC-ESI-MS) were the analytical methods used for structural confirmation of the products. There were eighteen 1,4-naphthoquinone derivatives that were successfully synthesised using ethanolic solutions. Unfortunately, attempts to synthesise 1,4-naphthoquinones in reactions involving 2-(trifluoro-methyl)aniline and 2-isopropyl-5-methylphenol were unsuccessful, presumably due to steric hindrance by the bulky ortho-substituents. Although the aims of the synthetic procedures were to obtain both mono- and disubstituted products by nucleophilic displacement of the chlorine atom(s) of 2,3-dichloro-1,4- naphthoquinone, only monosubstituted products were obtained from substitution with aniline and phenol nucleophiles. Thiol nucleophiles, however, selectively yielded disubstituted products only. Synthesised naphthoquinone derivatives were tested against Trypanosoma brucei and calculation of the EC₅₀ values from the obtained dose-response curves was carried out using the four parametric equation. All the 1,4-naphthoquinones showed a degree of potency, except compounds 1b, 3c and 3e, which had little or lack of potency. Structure-activity relationship studies (SARs and QSARs) were carried out to determine which structural features or functional group substituents of the naphthoquinone derivatives contribute or take away from the desired anti-trypanosomal activity. It was found that compounds with the best in vitro anti-trypanosomal potencies in the series of analogous 1,4-naphthoquinone derivatives had EC₅₀ values in the range 2.137 to 2.884 μM. The most potent compound in the series was 2-chloro-3-(4-(trifluoromethyl)phenylamino)-1,4- naphthoquinone 1e; but it was 142-fold less potent than the reference standard of melarsoprol.
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Aspects of the bioavailability of topical corticosteroid formulations
- Authors: Magnus, Ashley Denis
- Date: 2013-02-12
- Subjects: Adrenocortical hormones -- Therapeutic use , Dermatologic agents , Transdermal medication -- Evaluation , Dermatopharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3843 , http://hdl.handle.net/10962/d1009516 , Adrenocortical hormones -- Therapeutic use , Dermatologic agents , Transdermal medication -- Evaluation , Dermatopharmacology
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17-valer ate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base c aused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained f r om the systematic stUdies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Authors: Magnus, Ashley Denis
- Date: 2013-02-12
- Subjects: Adrenocortical hormones -- Therapeutic use , Dermatologic agents , Transdermal medication -- Evaluation , Dermatopharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3843 , http://hdl.handle.net/10962/d1009516 , Adrenocortical hormones -- Therapeutic use , Dermatologic agents , Transdermal medication -- Evaluation , Dermatopharmacology
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17-valer ate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base c aused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained f r om the systematic stUdies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
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The development and assessment of sustained release nevirapine tablets
- Authors: Mwila, Chiluba
- Date: 2013
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54667 , vital:26598
- Description: The use of antiretroviral (ARV) agents in the management of HIV/AIDS has significantly improved the lifestyle and wellbeing of patients. Despite the success that has been achieved with the use of ARV therapy, the occurrence of adverse effects and unpredictable bioavailability associated with most of these drugs remains a major concern. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is used in combination with other ARV compounds for the treatment of HIV-1 infections. It is also used for the prevention of mother to child transmission of the HIV-1 virus. NVP is a Biopharmaceutics Classification System (BCS) Class II compound. Although NVP exhibits good oral absorption, it induces self-metabolism leading to low and sometimes unpredictable bioavailability. NVP is commercially available as an immediate release and extended release dosage form, viz., Viramune® XR. Formulation of a generic sustained release (SR) dosage form for once daily dosing would result in delivery of constant amount of the drug to the circulation, reduce dose related adverse effects, improve patient compliance to medication and reduce the costs of therapy. A simple RP-HPLC method was developed and optimised using a central composite design approach. The method was validated using ICH guidelines and was found to be linear, precise, specific and accurate for the analysis of NVP both in bulk and dosage forms. Direct compression was used as the method of tablet manufacture. Different polymers were assessed for suitability as rate retarding polymers and included Methocel® K4M, Carbopol® 71G NF and Eudragit® RSPO. Powder blends were assessed for flow properties using the angle of repose, bulk and tapped density, Carr’s Compressibility index and Hausner’s ratio. The traditional approach of changing the amount of polymers and diluents systematically to achieve a desired NVP release profile was used for the development of a preliminary formulation. Response surface methodology was used for the optimisation of the formulation using a Box-Behnken quadratic design. Physical characteristics of the tablets such as thickness, weight, hardness, tensile strength and friability were assessed and the tablets passed Pharmacopoeial testing. NVP assay and content uniformity were assessed using a validated RP-HPLC method. Initially, USP Apparatus 2 was used to study NVP release over a 24 hour period and subsequently dissolution studies were performed using USP Apparatus 3 as it can be used to simulate GIT conditions. The dissolution profiles generated were used to determine the agitation rate for USP Apparatus 3 that would be equivalent to an agitation rate of 50 rpm when using USP Apparatus 2. The effect of the mesh screen pore size, buffer molarity strength and concentration of surfactant on NVP release were also investigated in order to select discriminatory dissolution test conditions for the test formulation. Dissolution profiles were compared to those of the commercially available Viramune® XR using the FDA recommended difference (f1) and similarity (f2) factors. The calculated values for f1 and f2 revealed that the dissolution profile for the optimised formulation that was identified was statistically similar to Viramune® XR. In vitro release data were fitted to different kinetic models to study the release kinetics of NVP. The overall mechanism of NVP release was best described using the Korsmeyer-Peppas diffusion exponent value, n. NVP release was found to be anomalous, implying that the release was influenced by a combination of diffusion, swelling and polymer chain relaxation. The Hixson-Crowell model revealed that there was constant change in surface area of the dosage form suggesting that erosion and swelling were significant factors affecting NVP release from the hydrophilic matrix technology. The release kinetics data were also used to design the optimised formulation. Tablets manufactured using the optimised formulation were subjected to water uptake and erosion studies and the results revealed that swelling and erosion occur simultaneously. The effects of pH and molarity on the swelling and erosion of the tablets were also investigated. The data suggest that increase in pH resulted in a slight increase in swelling while an increase in molarity did not have a significant effect on swelling. The change in pH did not have a significant effect on erosion while an increase in molarity strength resulted in a decrease in matrix erosion. The effect of HPMC grade on swelling, erosion and NVP release revealed that the grade of HPMC used had a significant effect on NVP release, with the release rate decreasing, swelling increasing and erosion decreasing as the viscosity of the HPMC grade increased. The effect of the particle size of MCC on NVP release was also studied by manufacturing tablets containing different grades of MCC and these studies revealed that particle size did not appear to have a significant effect on NVP release. Similarly the use of different types of lactose did not appear to have a significant impact on NVP release. In conclusion a sustained release NVP tablet formulation that has the potential for further development and optimisation has been developed, assessed and manufactured successfully and has been shown to exhibit similar dissolution behaviour to Viramune® XR, a commercially available NVP extended release product.
- Full Text:
- Authors: Mwila, Chiluba
- Date: 2013
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54667 , vital:26598
- Description: The use of antiretroviral (ARV) agents in the management of HIV/AIDS has significantly improved the lifestyle and wellbeing of patients. Despite the success that has been achieved with the use of ARV therapy, the occurrence of adverse effects and unpredictable bioavailability associated with most of these drugs remains a major concern. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is used in combination with other ARV compounds for the treatment of HIV-1 infections. It is also used for the prevention of mother to child transmission of the HIV-1 virus. NVP is a Biopharmaceutics Classification System (BCS) Class II compound. Although NVP exhibits good oral absorption, it induces self-metabolism leading to low and sometimes unpredictable bioavailability. NVP is commercially available as an immediate release and extended release dosage form, viz., Viramune® XR. Formulation of a generic sustained release (SR) dosage form for once daily dosing would result in delivery of constant amount of the drug to the circulation, reduce dose related adverse effects, improve patient compliance to medication and reduce the costs of therapy. A simple RP-HPLC method was developed and optimised using a central composite design approach. The method was validated using ICH guidelines and was found to be linear, precise, specific and accurate for the analysis of NVP both in bulk and dosage forms. Direct compression was used as the method of tablet manufacture. Different polymers were assessed for suitability as rate retarding polymers and included Methocel® K4M, Carbopol® 71G NF and Eudragit® RSPO. Powder blends were assessed for flow properties using the angle of repose, bulk and tapped density, Carr’s Compressibility index and Hausner’s ratio. The traditional approach of changing the amount of polymers and diluents systematically to achieve a desired NVP release profile was used for the development of a preliminary formulation. Response surface methodology was used for the optimisation of the formulation using a Box-Behnken quadratic design. Physical characteristics of the tablets such as thickness, weight, hardness, tensile strength and friability were assessed and the tablets passed Pharmacopoeial testing. NVP assay and content uniformity were assessed using a validated RP-HPLC method. Initially, USP Apparatus 2 was used to study NVP release over a 24 hour period and subsequently dissolution studies were performed using USP Apparatus 3 as it can be used to simulate GIT conditions. The dissolution profiles generated were used to determine the agitation rate for USP Apparatus 3 that would be equivalent to an agitation rate of 50 rpm when using USP Apparatus 2. The effect of the mesh screen pore size, buffer molarity strength and concentration of surfactant on NVP release were also investigated in order to select discriminatory dissolution test conditions for the test formulation. Dissolution profiles were compared to those of the commercially available Viramune® XR using the FDA recommended difference (f1) and similarity (f2) factors. The calculated values for f1 and f2 revealed that the dissolution profile for the optimised formulation that was identified was statistically similar to Viramune® XR. In vitro release data were fitted to different kinetic models to study the release kinetics of NVP. The overall mechanism of NVP release was best described using the Korsmeyer-Peppas diffusion exponent value, n. NVP release was found to be anomalous, implying that the release was influenced by a combination of diffusion, swelling and polymer chain relaxation. The Hixson-Crowell model revealed that there was constant change in surface area of the dosage form suggesting that erosion and swelling were significant factors affecting NVP release from the hydrophilic matrix technology. The release kinetics data were also used to design the optimised formulation. Tablets manufactured using the optimised formulation were subjected to water uptake and erosion studies and the results revealed that swelling and erosion occur simultaneously. The effects of pH and molarity on the swelling and erosion of the tablets were also investigated. The data suggest that increase in pH resulted in a slight increase in swelling while an increase in molarity did not have a significant effect on swelling. The change in pH did not have a significant effect on erosion while an increase in molarity strength resulted in a decrease in matrix erosion. The effect of HPMC grade on swelling, erosion and NVP release revealed that the grade of HPMC used had a significant effect on NVP release, with the release rate decreasing, swelling increasing and erosion decreasing as the viscosity of the HPMC grade increased. The effect of the particle size of MCC on NVP release was also studied by manufacturing tablets containing different grades of MCC and these studies revealed that particle size did not appear to have a significant effect on NVP release. Similarly the use of different types of lactose did not appear to have a significant impact on NVP release. In conclusion a sustained release NVP tablet formulation that has the potential for further development and optimisation has been developed, assessed and manufactured successfully and has been shown to exhibit similar dissolution behaviour to Viramune® XR, a commercially available NVP extended release product.
- Full Text:
The isolation and characterisation of secondary metabolites from selected South African marine red algae (Rhodophyta)
- Authors: Fakee, Jameel
- Date: 2013
- Subjects: Metabolites Marine algae -- South Africa Marine algae -- Therapeutic use Metabolites -- Therapeutic use Marine metabolites Plocamocera Red algae Laurencia Delisea flaccida
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3733 , http://hdl.handle.net/10962/d1001472
- Description: Secondary metabolites from natural sources are fast growing as popular drug leads. The structural novelty and favourable biological activity that these compounds display contribute to their popularity as drugs of the future. Examples of such compounds include the potent anticancer drug paclitaxel isolated from the bark of a yew tree as well as the more commonly known analgesic aspirin which stems from the bark of the willow tree. The biological activities exhibited by these secondary metabolites are vast and range from antimicrobial to anticancer activity to mention but a few. As a result, the isolation of novel compounds from natural sources is on the rise. The South African seaboard is home to a wealth of various marine algal species which produce fascinating secondary metabolites. For example, Portierria hornemanii was shown to produce halomon, a halogenated monoterpene which has displayed promising cytotoxic activity. This study thus focused primarily on pursuing novel compounds from three endemic South African marine algal species which have never been analysed previously from a chemical perspective. These are Plocamium rigidum (Bory de Saint-Vincent), Laurencia natalensis (Kylin) and Delisea flaccida (Suhr) Papenfuss. Four known compounds and one new halogenated monoterpene, (2E,5E,7Z)-8-chloro- 7-(dichloromethyl)-4-hydroxy-3-methylocta-2,5,7-trienal, were isolated from Plocamium rigidum. The breast cancer (MCF-7 cell line) inhibitory activity for these compounds was assessed and it was observed that an increase in the lipophilic nature of the compounds produced more favourable IC50 values. A pre-cursor to bromofucin type compounds, cis-laurencenyne, was isolated from Laurencia natalensis, as well as a new acetoxy chamigrane type compound, 4-bromo- 3,10-dichloro-7-hydroxy-3,7,11,11-tetramethylspiro [6.6] undec-1-yl acetate. Delisea flaccida was seen to contain two known bromofuranone type compounds isolated as an isomeric mixture, 1-[(5Z)-4-bromo-5-(bromomethylidene)-2-oxo-2,5- dihydrofuran-3-yl] butyl acetate and 1-[(5E)-4-bromo-5-(bromomethylidene)-2- oxo-2,5-dihydrofuran-3-yl]butyl acetate. These compounds are famous for their ability to inhibit bacterial biofilm production and they have been isolated before from an Australian Delisea spp , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Authors: Fakee, Jameel
- Date: 2013
- Subjects: Metabolites Marine algae -- South Africa Marine algae -- Therapeutic use Metabolites -- Therapeutic use Marine metabolites Plocamocera Red algae Laurencia Delisea flaccida
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3733 , http://hdl.handle.net/10962/d1001472
- Description: Secondary metabolites from natural sources are fast growing as popular drug leads. The structural novelty and favourable biological activity that these compounds display contribute to their popularity as drugs of the future. Examples of such compounds include the potent anticancer drug paclitaxel isolated from the bark of a yew tree as well as the more commonly known analgesic aspirin which stems from the bark of the willow tree. The biological activities exhibited by these secondary metabolites are vast and range from antimicrobial to anticancer activity to mention but a few. As a result, the isolation of novel compounds from natural sources is on the rise. The South African seaboard is home to a wealth of various marine algal species which produce fascinating secondary metabolites. For example, Portierria hornemanii was shown to produce halomon, a halogenated monoterpene which has displayed promising cytotoxic activity. This study thus focused primarily on pursuing novel compounds from three endemic South African marine algal species which have never been analysed previously from a chemical perspective. These are Plocamium rigidum (Bory de Saint-Vincent), Laurencia natalensis (Kylin) and Delisea flaccida (Suhr) Papenfuss. Four known compounds and one new halogenated monoterpene, (2E,5E,7Z)-8-chloro- 7-(dichloromethyl)-4-hydroxy-3-methylocta-2,5,7-trienal, were isolated from Plocamium rigidum. The breast cancer (MCF-7 cell line) inhibitory activity for these compounds was assessed and it was observed that an increase in the lipophilic nature of the compounds produced more favourable IC50 values. A pre-cursor to bromofucin type compounds, cis-laurencenyne, was isolated from Laurencia natalensis, as well as a new acetoxy chamigrane type compound, 4-bromo- 3,10-dichloro-7-hydroxy-3,7,11,11-tetramethylspiro [6.6] undec-1-yl acetate. Delisea flaccida was seen to contain two known bromofuranone type compounds isolated as an isomeric mixture, 1-[(5Z)-4-bromo-5-(bromomethylidene)-2-oxo-2,5- dihydrofuran-3-yl] butyl acetate and 1-[(5E)-4-bromo-5-(bromomethylidene)-2- oxo-2,5-dihydrofuran-3-yl]butyl acetate. These compounds are famous for their ability to inhibit bacterial biofilm production and they have been isolated before from an Australian Delisea spp , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
An assessment of African traditional medicines in pregnancy and on birth outcomes: pharmacists' perceptions of complementary medicines in pregnancy
- Authors: Mupfumira, Rudo
- Date: 2012
- Subjects: Traditional medicine -- South Africa Pharmacists -- Attitudes -- South Africa Medical ethics -- South Africa Medical anthropology -- South Africa Alternative medicine -- South Africa Prenatal care -- South Africa Pregnancy -- South Africa Abnormalities, Human -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3778 , http://hdl.handle.net/10962/d1003256
- Description: Increasing numbers of medicines are being used by pregnant South African women in the public sector during pregnancy, for the treatment of different biomedical and supernatural disease states and conditions. The motivation for the research is to support the development of more local pregnancy registries in order to strengthen evidence for the safety and efficacy of medicines used in pregnancy. A mixed methods approach was used. Women in their ninth month of pregnancy in a public sector setting, and four community pharmacists were identified. The women who met the inclusion criteria were recruited. One in-depth semi-structured interview was conducted with each woman before giving birth and data on their pregnancy outcomes were collected after labour. Coincidentally, the mother of one of the participants was found to be a traditional healer. She was also interviewed on the topic. A structured questionnaire was administered to the pharmacists. Ten pregnant women between the ages of 19 to 39 who had used or were using a traditional medicine during the pregnancy were recruited. All the participants had had at least one antenatal check up during their pregnancy with one having attended five times. No abnormal results were reported from any of the check ups or tests done during the visits. All of them had been to school and had at least Standard 8/Grade 10 education. Ten babies were seen between one and four days postpartum and no birth defects were obvious or were reported for any of them. The traditional healer did not provide additional information to what the women had said and confirmed that some of the practices the women reported were known to her as traditional medicine practices. All four pharmacists indicated that they considered complementary and alternative medicines (CAMs) to be “somewhat effective” and sold them at their pharmacies although none of them were aware of whether or not they were registered with the MCC. None of the pharmacists appeared to have an in-depth knowledge of traditional, complementary and alternative medicines (TCAMs). All four pharmacists said that it is important to have a basic understanding of TCAMs before using them, although they did not agree on the reasons for this. All of them felt that pharmacists have a professional responsibility to provide information on TCAMs (especially herbal preparations) and two felt that providing this information is part of a medical doctors’ responsibility. No harm from taking TCAMs could be shown. However herbal medicines have numerous ingredients some of which are unknown and taking these medicines is risky. The pharmacists in this sample were unsure whether they were accessing unreliable CAM information. Reliable sources of information and reference materials on CAMs to assist pharmacists and other healthcare professionals are needed. The apparent widespread use of TCAM in pregnancy indicates a need for documentation about its efficacy and safety. The establishing of TCAM pregnancy registries should seriously be considered. Due to the increase in CAM use, CAM education during pharmacists’ training as well as continuing professional development (CPD) in CAM for pharmacists in practice should be encouraged.
- Full Text:
- Authors: Mupfumira, Rudo
- Date: 2012
- Subjects: Traditional medicine -- South Africa Pharmacists -- Attitudes -- South Africa Medical ethics -- South Africa Medical anthropology -- South Africa Alternative medicine -- South Africa Prenatal care -- South Africa Pregnancy -- South Africa Abnormalities, Human -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3778 , http://hdl.handle.net/10962/d1003256
- Description: Increasing numbers of medicines are being used by pregnant South African women in the public sector during pregnancy, for the treatment of different biomedical and supernatural disease states and conditions. The motivation for the research is to support the development of more local pregnancy registries in order to strengthen evidence for the safety and efficacy of medicines used in pregnancy. A mixed methods approach was used. Women in their ninth month of pregnancy in a public sector setting, and four community pharmacists were identified. The women who met the inclusion criteria were recruited. One in-depth semi-structured interview was conducted with each woman before giving birth and data on their pregnancy outcomes were collected after labour. Coincidentally, the mother of one of the participants was found to be a traditional healer. She was also interviewed on the topic. A structured questionnaire was administered to the pharmacists. Ten pregnant women between the ages of 19 to 39 who had used or were using a traditional medicine during the pregnancy were recruited. All the participants had had at least one antenatal check up during their pregnancy with one having attended five times. No abnormal results were reported from any of the check ups or tests done during the visits. All of them had been to school and had at least Standard 8/Grade 10 education. Ten babies were seen between one and four days postpartum and no birth defects were obvious or were reported for any of them. The traditional healer did not provide additional information to what the women had said and confirmed that some of the practices the women reported were known to her as traditional medicine practices. All four pharmacists indicated that they considered complementary and alternative medicines (CAMs) to be “somewhat effective” and sold them at their pharmacies although none of them were aware of whether or not they were registered with the MCC. None of the pharmacists appeared to have an in-depth knowledge of traditional, complementary and alternative medicines (TCAMs). All four pharmacists said that it is important to have a basic understanding of TCAMs before using them, although they did not agree on the reasons for this. All of them felt that pharmacists have a professional responsibility to provide information on TCAMs (especially herbal preparations) and two felt that providing this information is part of a medical doctors’ responsibility. No harm from taking TCAMs could be shown. However herbal medicines have numerous ingredients some of which are unknown and taking these medicines is risky. The pharmacists in this sample were unsure whether they were accessing unreliable CAM information. Reliable sources of information and reference materials on CAMs to assist pharmacists and other healthcare professionals are needed. The apparent widespread use of TCAM in pregnancy indicates a need for documentation about its efficacy and safety. The establishing of TCAM pregnancy registries should seriously be considered. Due to the increase in CAM use, CAM education during pharmacists’ training as well as continuing professional development (CPD) in CAM for pharmacists in practice should be encouraged.
- Full Text:
Design and evaluation of illustrated information leaflets as an educational tool for low-literate asthma patients
- Authors: Wrench, Wendy Merle
- Date: 2012 , 2012-10-08
- Subjects: Asthma -- South Africa -- Study and teaching , Asthmatics -- South Africa -- Education
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3867 , http://hdl.handle.net/10962/d1016236
- Description: Asthma is a chronic non-communicable disease associated with an increase in morbidity, mortality and economic burden. Globally 300 million people have asthma and it is estimated that one in every 250 deaths worldwide are due to asthma. South Africa has the highest asthma prevalence (8.1%) in Africa and the disease is 18th in the top 20 causes of death. Inadequate home management, poor availability of health care, and poor transport and emergency services are recognised as important contributing factors. Patients with a low level of education and limited literacy skills may be unable to understand instructions on frequency and use of asthma medicines, which could result in unintentional non-adherence leading to serious complications and increased health care costs. The aim of this study was to investigate the impact of a tailored educational intervention on low-literate patients with asthma. Objectives to achieve this aim included designing patient information leaflets (PILs) containing information on asthma, management of asthma and asthma therapy, and using the PILs to educate low-literate asthma patients. A before-andafter intervention type design evaluated self-reported selected health-related quality of life measures, self-reported self-efficacy, knowledge of asthma and asthma management, knowledge of the use of metered dose inhalers (MDIs) and MDI technique. The acceptability and understanding of the tailored PILs was also investigated. Two simple, readable PILs containing pictograms were developed in English and then translated into isiXhosa, the home language of the majority of the target population. Various guidelines on the design of health-related information for people with low-literacy were consulted and input on the design was received from health care providers, patients and graphic artists. A pilot study was conducted at a local primary health care (PHC) clinic to evaluate the PILs and final modifications to the PILs were made based on feedback received. For the main study, patients were recruited from the KwaNonqubela PHC clinic in Alexandria in the Eastern Cape, South Africa. Patients were 18 years or older, dependent on public sector health care facilities, diagnosed with asthma, prescribed a MDI (beclomethasone and/or salbutamol) for at least one month and English or isiXhosa-speaking. The exclusion criterion for patients in this study was involvement in any other asthma educational intervention during the period of study. Interviewer-led structured questionnaires were administered to 55 patients at the baseline and follow-up. Data collected include demographics, brief medical history and current asthma medications. Self-efficacy and iii health-related quality of life were assessed. Knowledge of asthma and asthma management was evaluated, and the use of beclomethasone and/or salbutamol metered dose inhalers was assessed. The PIL ‘Understanding asthma and trigger factors of asthma’ formed part of the educational intervention to explain asthma and aspects related to its management. Inhaler technique was evaluated and corrected using the PIL ‘How to use your pump’ together with a demonstration of correct technique by the investigator. Follow-up interviews were conducted approximately four weeks after baseline. PIL acceptability, readability and understanding of each pictogram were investigated at follow-up only. The educational intervention resulted in a significant increase in mean knowledge of asthma from 52.7% at baseline to 75.5% at follow-up. Gender was not associated with knowledge, but there was a significant age effect at baseline only, with the younger patients achieving better knowledge results. In both phases, patients with higher education had improved scores. A significant increase (2.4% to 38.6%) in the number of patients taking the minimum recommended adult dose of beclomethasone was noted but it is a matter of concern that the majority of patients were taking less than this. Patient self-reports suggested a significant increase in adherence, with the number of patients taking beclomethasone daily increasing from 33.3% to 61.3%. Self-reported management and control of asthma improved and this was reflected by the enhanced HRQOL results. MDI technique also improved significantly with an increase in the mean number of correct steps from 4.6 ± 2.2 to 7.9 ± 2.7. Education had a significant effect on MDI technique with more errors associated with lower educational status. There were no significant age or gender effects on the total number of correct steps in either phase. The illustrated PILs were received favourably with the majority of literate patients reporting that they were easy to read. Patients commented positively on the inclusion of pictograms and stated that the pictograms had served as aids in the understanding of asthma, trigger factors of asthma and correct MDI technique. The results of this study show that specially designed illustrated PILs can be an effective tool in educating low-literate patients with asthma. , Adobe Acrobat Pro 11.0.0 Paper Capture Plug-in
- Full Text:
- Authors: Wrench, Wendy Merle
- Date: 2012 , 2012-10-08
- Subjects: Asthma -- South Africa -- Study and teaching , Asthmatics -- South Africa -- Education
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3867 , http://hdl.handle.net/10962/d1016236
- Description: Asthma is a chronic non-communicable disease associated with an increase in morbidity, mortality and economic burden. Globally 300 million people have asthma and it is estimated that one in every 250 deaths worldwide are due to asthma. South Africa has the highest asthma prevalence (8.1%) in Africa and the disease is 18th in the top 20 causes of death. Inadequate home management, poor availability of health care, and poor transport and emergency services are recognised as important contributing factors. Patients with a low level of education and limited literacy skills may be unable to understand instructions on frequency and use of asthma medicines, which could result in unintentional non-adherence leading to serious complications and increased health care costs. The aim of this study was to investigate the impact of a tailored educational intervention on low-literate patients with asthma. Objectives to achieve this aim included designing patient information leaflets (PILs) containing information on asthma, management of asthma and asthma therapy, and using the PILs to educate low-literate asthma patients. A before-andafter intervention type design evaluated self-reported selected health-related quality of life measures, self-reported self-efficacy, knowledge of asthma and asthma management, knowledge of the use of metered dose inhalers (MDIs) and MDI technique. The acceptability and understanding of the tailored PILs was also investigated. Two simple, readable PILs containing pictograms were developed in English and then translated into isiXhosa, the home language of the majority of the target population. Various guidelines on the design of health-related information for people with low-literacy were consulted and input on the design was received from health care providers, patients and graphic artists. A pilot study was conducted at a local primary health care (PHC) clinic to evaluate the PILs and final modifications to the PILs were made based on feedback received. For the main study, patients were recruited from the KwaNonqubela PHC clinic in Alexandria in the Eastern Cape, South Africa. Patients were 18 years or older, dependent on public sector health care facilities, diagnosed with asthma, prescribed a MDI (beclomethasone and/or salbutamol) for at least one month and English or isiXhosa-speaking. The exclusion criterion for patients in this study was involvement in any other asthma educational intervention during the period of study. Interviewer-led structured questionnaires were administered to 55 patients at the baseline and follow-up. Data collected include demographics, brief medical history and current asthma medications. Self-efficacy and iii health-related quality of life were assessed. Knowledge of asthma and asthma management was evaluated, and the use of beclomethasone and/or salbutamol metered dose inhalers was assessed. The PIL ‘Understanding asthma and trigger factors of asthma’ formed part of the educational intervention to explain asthma and aspects related to its management. Inhaler technique was evaluated and corrected using the PIL ‘How to use your pump’ together with a demonstration of correct technique by the investigator. Follow-up interviews were conducted approximately four weeks after baseline. PIL acceptability, readability and understanding of each pictogram were investigated at follow-up only. The educational intervention resulted in a significant increase in mean knowledge of asthma from 52.7% at baseline to 75.5% at follow-up. Gender was not associated with knowledge, but there was a significant age effect at baseline only, with the younger patients achieving better knowledge results. In both phases, patients with higher education had improved scores. A significant increase (2.4% to 38.6%) in the number of patients taking the minimum recommended adult dose of beclomethasone was noted but it is a matter of concern that the majority of patients were taking less than this. Patient self-reports suggested a significant increase in adherence, with the number of patients taking beclomethasone daily increasing from 33.3% to 61.3%. Self-reported management and control of asthma improved and this was reflected by the enhanced HRQOL results. MDI technique also improved significantly with an increase in the mean number of correct steps from 4.6 ± 2.2 to 7.9 ± 2.7. Education had a significant effect on MDI technique with more errors associated with lower educational status. There were no significant age or gender effects on the total number of correct steps in either phase. The illustrated PILs were received favourably with the majority of literate patients reporting that they were easy to read. Patients commented positively on the inclusion of pictograms and stated that the pictograms had served as aids in the understanding of asthma, trigger factors of asthma and correct MDI technique. The results of this study show that specially designed illustrated PILs can be an effective tool in educating low-literate patients with asthma. , Adobe Acrobat Pro 11.0.0 Paper Capture Plug-in
- Full Text:
Development, assessment and optimisation of oral famciclovir formulations for paediatric use
- Authors: Magnus, Laura
- Date: 2012
- Subjects: Drugs -- Dosage forms , Drugs -- Analysis , Capsules (Pharmacy) , Antiviral agents , Pediatrics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3870 , http://hdl.handle.net/10962/d1018244
- Description: Many Active Pharmaceutical Ingredients (API) such as the antiviral agent famciclovir (FCV) are required for paediatric treatment but are not commercially available in age-appropriate dosage forms. It is common practice to prepare oral liquid dosage forms using commercially available tablets, capsules or powdered API and then dispersing or dissolving the crushed and/or powdered materials in a vehicle that the patient can swallow. Vehicles that are commonly used for this purpose include methylcellulose, syrup or combinations of these carriers where possible or commercially available suspending agents such as Ora-Sweet®, if available, can be used. However, several critical factors are overlooked when manufacturing extemporaneous formulations including, but not limited to, physical and chemical properties of the API, excipients, compatibility, stability and bioavailability issues. A stability-indicating High Performance Liquid Chromatography (HPLC) method for the analysis of FCV was developed and validated according to the International Conference on Harmonization (ICH) guidelines. The method is sensitive, selective, precise, accurate and linear over the concentration range 2-120 μg/ml. The stability of 25 mg/ml FCV formulations was assessed in vehicles manufactured from syrup simplex, hydroxypropyl methylcellulose (HPMC), Ora-Sweet® and an aqueous buffer (pH 6) following storage at 25 °C/60% RH and 40 °C/75% RH over six (6) to eight (8) weeks. The shelf life of the products was calculated as the longest period of storage for approximately 90% of the added FCV to be recovered. Formulations were manufactured using syrup simplex or HPMC with methylparaben and propylparaben individually or in combination and with sodium metabisulphite, ascorbic acid or citric acid as antioxidants. The resultant products were subject to quality control analysis for API content, viscosity, pH and appearance and the resultant data were subject to statistical analysis. The degradation rates were calculated for each product and a degradation profile plotted. The degradation rates of FCV in extemporaneous formulations were compared to those of FCV manufactured using a commercially available suspending agent and a buffered vehicle. FCV undergoes major degradation in the presence of sucrose, as observed for formulations in which the vehicle was syrup and Ora-Sweet®. FCV was found to be most stable when dissolved/dispersed in an HPMC vehicle incorporating sodium metabisulphite and a combination of parabens. The formulation that exhibited the maximum stability was manufactured using an aqueous solution buffered to pH 6. Due to the enhanced stability of FCV when added to a buffered vehicle a formulation in which an HPMC vehicle buffered to pH 6 with sodium metabisulphite, methylparaben and propylparaben was selected for optimisation using a Central Composite Design approach (CCD). In this way it was possible to establish a relationship between input variables such as pH, % w/v HPMC, % w/v antioxidant and % w/v preservative and the responses selected for monitoring by means of response surface modelling. A quadratic model was found to be the most appropriate to describe the relationship between input and output variables. Thirty batches of product were randomly manufactured according to the CCD and analysed to establish the stability in respect of viscosity, pH and the amount of FCV remaining following storage and the data were fitted to models using Design-Expert® software. A correlation between input variables and the responses was best described by a quadratic polynomial model. Analysis of Variance indicated that the response surface models were significant (P-value < 0.0001). The pH to which a FCV formulation was buffered was the most significant factor to effect the % drug content and the ultimate pH of the formulation, while the % w/v HPMC had the most significant effect on the viscosity of the product. The optimum composition for the manufacture of an oral liquid FCV formulation was predicted using the optimisation function of the Design-Expert® software. A low % error of prediction was established, indicating that the model is robust and that RSM is an appropriate formulation optimisation tool as it has a high prognostic ability. A liquid FCV formulation was developed, optimised and found to be suitable for its intended purpose. However further optimisation is required in respect of colourants, sweeteners and/or flavourants. The approach followed is useful in ensuring the development of quality products and can be applied in future.
- Full Text:
- Authors: Magnus, Laura
- Date: 2012
- Subjects: Drugs -- Dosage forms , Drugs -- Analysis , Capsules (Pharmacy) , Antiviral agents , Pediatrics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3870 , http://hdl.handle.net/10962/d1018244
- Description: Many Active Pharmaceutical Ingredients (API) such as the antiviral agent famciclovir (FCV) are required for paediatric treatment but are not commercially available in age-appropriate dosage forms. It is common practice to prepare oral liquid dosage forms using commercially available tablets, capsules or powdered API and then dispersing or dissolving the crushed and/or powdered materials in a vehicle that the patient can swallow. Vehicles that are commonly used for this purpose include methylcellulose, syrup or combinations of these carriers where possible or commercially available suspending agents such as Ora-Sweet®, if available, can be used. However, several critical factors are overlooked when manufacturing extemporaneous formulations including, but not limited to, physical and chemical properties of the API, excipients, compatibility, stability and bioavailability issues. A stability-indicating High Performance Liquid Chromatography (HPLC) method for the analysis of FCV was developed and validated according to the International Conference on Harmonization (ICH) guidelines. The method is sensitive, selective, precise, accurate and linear over the concentration range 2-120 μg/ml. The stability of 25 mg/ml FCV formulations was assessed in vehicles manufactured from syrup simplex, hydroxypropyl methylcellulose (HPMC), Ora-Sweet® and an aqueous buffer (pH 6) following storage at 25 °C/60% RH and 40 °C/75% RH over six (6) to eight (8) weeks. The shelf life of the products was calculated as the longest period of storage for approximately 90% of the added FCV to be recovered. Formulations were manufactured using syrup simplex or HPMC with methylparaben and propylparaben individually or in combination and with sodium metabisulphite, ascorbic acid or citric acid as antioxidants. The resultant products were subject to quality control analysis for API content, viscosity, pH and appearance and the resultant data were subject to statistical analysis. The degradation rates were calculated for each product and a degradation profile plotted. The degradation rates of FCV in extemporaneous formulations were compared to those of FCV manufactured using a commercially available suspending agent and a buffered vehicle. FCV undergoes major degradation in the presence of sucrose, as observed for formulations in which the vehicle was syrup and Ora-Sweet®. FCV was found to be most stable when dissolved/dispersed in an HPMC vehicle incorporating sodium metabisulphite and a combination of parabens. The formulation that exhibited the maximum stability was manufactured using an aqueous solution buffered to pH 6. Due to the enhanced stability of FCV when added to a buffered vehicle a formulation in which an HPMC vehicle buffered to pH 6 with sodium metabisulphite, methylparaben and propylparaben was selected for optimisation using a Central Composite Design approach (CCD). In this way it was possible to establish a relationship between input variables such as pH, % w/v HPMC, % w/v antioxidant and % w/v preservative and the responses selected for monitoring by means of response surface modelling. A quadratic model was found to be the most appropriate to describe the relationship between input and output variables. Thirty batches of product were randomly manufactured according to the CCD and analysed to establish the stability in respect of viscosity, pH and the amount of FCV remaining following storage and the data were fitted to models using Design-Expert® software. A correlation between input variables and the responses was best described by a quadratic polynomial model. Analysis of Variance indicated that the response surface models were significant (P-value < 0.0001). The pH to which a FCV formulation was buffered was the most significant factor to effect the % drug content and the ultimate pH of the formulation, while the % w/v HPMC had the most significant effect on the viscosity of the product. The optimum composition for the manufacture of an oral liquid FCV formulation was predicted using the optimisation function of the Design-Expert® software. A low % error of prediction was established, indicating that the model is robust and that RSM is an appropriate formulation optimisation tool as it has a high prognostic ability. A liquid FCV formulation was developed, optimised and found to be suitable for its intended purpose. However further optimisation is required in respect of colourants, sweeteners and/or flavourants. The approach followed is useful in ensuring the development of quality products and can be applied in future.
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Foreign reference products in the registration of generic medicines in South Africa a case study
- Authors: Hwengwere, Eldinah
- Date: 2012
- Subjects: Generic drugs -- Law and legislation -- South Africa Case studies Generic drugs -- South Africa Case studies Drugs -- Law and legislation -- South Africa Case studies Pharmacy -- Law and legislation -- South Africa Case studies
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3762 , http://hdl.handle.net/10962/d1003240
- Description: Introduction: Due to the increase in healthcare costs, generic medicines have been adopted for used in both developed and developing countries. When a generic or ‘multisource interchangeable medicine’ is to be registered, studies that prove that the generic is equivalent to the Innovator Product (IP) are used. The generic medicine is required to prove that it will mirror the IP in terms of safety, quality and efficacy and, in South Africa, the Medicines Control Council (MCC) ensures that generic medicines meet these requirements. Generic medicines may be registered using bioequivalence data obtained from comparison with a domestic reference product (usually the local innovator product) or in certain cases, a foreign reference product (FRP). The bioequivalence data can either be from in vivo or in vitro studies. The MCC guidelines require that for modified release preparations, in vivo bioequivalence studies are done for approval of registration; the exception being if a proportionally higher dose has already been registered. No information is currently given to prescribers and dispensers or to the public about whether a generic product was registered against a foreign or domestic reference product. Aims and Objectives: 1.) To determine the number of generic medicines in a predetermined sample registered using a FRP as comparator and to document the transparency of pharmaceutical companies when approached to disclose information regarding the registration of these products. 2.) To describe and document the use of the Promotion of Access to Information Act (Act 2 of 2000) [PAIA] from the perspective of a ‘layperson’ in the context of medicines’ regulation, in both private and public bodies. Methods: 20 modified release and Biopharmaceutics Classification System (BCS) class IV products were selected from the ‘generics dictionary’ – a commercial publication – and letters were sent to the manufacturers of the products requesting information about the tests done to prove equivalence and whether they were performed against a domestic or foreign reference product. The same information was also requested from the MCC. The requests were all made using the Promotion of Access to Information Act (PAIA). Results: Nine companies were represented by the 20 products chosen. Information was obtained about thirteen products. Ten of these products were registered using FRPs. Four products were registered based only on comparative dissolution studies. Four companies provided the requested information, two companies responded by refusing the requests and three did not respond at all. The MCC refused the request for information even after an internal appeal was lodged. Conclusions: The Promotion of Access to information Act was unsuccessful in obtaining information from the public body, and partly successful in obtaining it from the private bodies. While the title of the Act seems to indicate that the Act can be used to obtain information as such, it only provides for access to specified records. The MCC and the pharmaceutical companies involved in the study were under no obligation to provide the information as the request had not complied with PAIA requirements. The use of FRPs for registration is a reality in the pharmaceutical industry in South Africa. Neither the public nor healthcare professionals who prescribe medicines or who are involved in dispensing generic medicines as substitutes are aware of whether or not a FRP has been used to register a generic. Interchangeability cannot necessarily be guaranteed if the reference product was not proven equivalent to the local innovator product. It is debatable as to whether or not this information would be of any particular benefit to members of the public. Prescribers may choose to write ‘no substitution’ on their prescriptions if they were unconvinced that an FRP is acceptable. This could have consequences for healthcare costs. Dispensers are the most vulnerable in South Africa as they are obliged by law to substitute generic medicines when innovator medicines have been prescribed. Dispensers’ views on the acceptability of the use of FRPs can be seen as irrelevant. In the end, as this study demonstrates, the only option in the present situation is to rely entirely on the MCC’s rigour in assessing applications for registration of generic medicines.
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- Authors: Hwengwere, Eldinah
- Date: 2012
- Subjects: Generic drugs -- Law and legislation -- South Africa Case studies Generic drugs -- South Africa Case studies Drugs -- Law and legislation -- South Africa Case studies Pharmacy -- Law and legislation -- South Africa Case studies
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3762 , http://hdl.handle.net/10962/d1003240
- Description: Introduction: Due to the increase in healthcare costs, generic medicines have been adopted for used in both developed and developing countries. When a generic or ‘multisource interchangeable medicine’ is to be registered, studies that prove that the generic is equivalent to the Innovator Product (IP) are used. The generic medicine is required to prove that it will mirror the IP in terms of safety, quality and efficacy and, in South Africa, the Medicines Control Council (MCC) ensures that generic medicines meet these requirements. Generic medicines may be registered using bioequivalence data obtained from comparison with a domestic reference product (usually the local innovator product) or in certain cases, a foreign reference product (FRP). The bioequivalence data can either be from in vivo or in vitro studies. The MCC guidelines require that for modified release preparations, in vivo bioequivalence studies are done for approval of registration; the exception being if a proportionally higher dose has already been registered. No information is currently given to prescribers and dispensers or to the public about whether a generic product was registered against a foreign or domestic reference product. Aims and Objectives: 1.) To determine the number of generic medicines in a predetermined sample registered using a FRP as comparator and to document the transparency of pharmaceutical companies when approached to disclose information regarding the registration of these products. 2.) To describe and document the use of the Promotion of Access to Information Act (Act 2 of 2000) [PAIA] from the perspective of a ‘layperson’ in the context of medicines’ regulation, in both private and public bodies. Methods: 20 modified release and Biopharmaceutics Classification System (BCS) class IV products were selected from the ‘generics dictionary’ – a commercial publication – and letters were sent to the manufacturers of the products requesting information about the tests done to prove equivalence and whether they were performed against a domestic or foreign reference product. The same information was also requested from the MCC. The requests were all made using the Promotion of Access to Information Act (PAIA). Results: Nine companies were represented by the 20 products chosen. Information was obtained about thirteen products. Ten of these products were registered using FRPs. Four products were registered based only on comparative dissolution studies. Four companies provided the requested information, two companies responded by refusing the requests and three did not respond at all. The MCC refused the request for information even after an internal appeal was lodged. Conclusions: The Promotion of Access to information Act was unsuccessful in obtaining information from the public body, and partly successful in obtaining it from the private bodies. While the title of the Act seems to indicate that the Act can be used to obtain information as such, it only provides for access to specified records. The MCC and the pharmaceutical companies involved in the study were under no obligation to provide the information as the request had not complied with PAIA requirements. The use of FRPs for registration is a reality in the pharmaceutical industry in South Africa. Neither the public nor healthcare professionals who prescribe medicines or who are involved in dispensing generic medicines as substitutes are aware of whether or not a FRP has been used to register a generic. Interchangeability cannot necessarily be guaranteed if the reference product was not proven equivalent to the local innovator product. It is debatable as to whether or not this information would be of any particular benefit to members of the public. Prescribers may choose to write ‘no substitution’ on their prescriptions if they were unconvinced that an FRP is acceptable. This could have consequences for healthcare costs. Dispensers are the most vulnerable in South Africa as they are obliged by law to substitute generic medicines when innovator medicines have been prescribed. Dispensers’ views on the acceptability of the use of FRPs can be seen as irrelevant. In the end, as this study demonstrates, the only option in the present situation is to rely entirely on the MCC’s rigour in assessing applications for registration of generic medicines.
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Illustrated medicines information for HIV/AIDS patients: influence on adherence,self-efficacy and health outcomes
- Authors: Barford, Kirsty-Lee
- Date: 2012
- Subjects: AIDS (Disease) -- Treatment -- South Africa , HIV infections -- Treatment -- South Africa , AIDS (Disease) -- Patients -- South Africa , HIV-positive persons -- South Africa , AIDS (Disease) -- Study and teaching -- South Africa , Antiretroviral agents -- South Africa , Communication in medicine -- South Africa , Communication in public health -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3863 , http://hdl.handle.net/10962/d1015678
- Description: South Africa has an estimated 920 000 patients on antiretrovirals (ARVs), the largest number of patients in any country. ARV therapy demands adherence levels in excess of 95% to avoid development of drug resistance, but adherence to ARV therapy is estimated to be only between 50% and 70%. Poor medication adherence is acknowledged as a major public health problem, reducing the effectiveness of therapy and promoting resistance to ARVs. More than two thirds of the South African population have marginal reading skills and this significantly influences a patient’s ability to read and understand health-related information. Patient education materials tailored for the South African population could be a useful aid in facilitating communication with patients and perhaps impact positively on their medicine-taking behaviour. This behaviour is influenced by patient knowledge, beliefs, attitudes and expectations and includes self-management, self-efficacy and adherence. Self-efficacy, which refers to patient confidence in the ability to self-manage medicine taking, is a key factor influencing adherence. This study aimed to develop illustrated patient information leaflets (PILs) and medicine labels for all first-line ARV regimens used in the public health sector in South Africa and, using a randomised control study design, to investigate the impact of these illustrated information materials on knowledge, medication-taking behaviours and health outcomes in HIV/AIDS patients taking ARVs. To achieve this aim, the objectives were to assess HIV/AIDS and ARV-related knowledge, as well as self-efficacy and adherence to ARV therapy; to assess the influence of demographic variables on knowledge, adherence and self-efficacy; to assess the influence of the information materials on knowledge, self-efficacy and adherence and to assess the association of knowledge with health outcomes. Medicine labels and PILs, both English and isiXhosa, were developed for ARV regimens 1a, 1b, 1c and 1d. The 8-item Morisky Medication Adherence Scale (MMAS-8) and HIV Treatment Adherence Self Efficacy Scale (HIV-ASES) instruments for measuring respectively adherence and self-efficacy, were modified to optimize clarity, simplicity and cultural acceptability and were translated into isiXhosa using a multi-stage translation-back translation. The questions and the rating scales, for both the MMAS and HIV-ASES, underwent preliminary qualitative evaluation in focus group discussions. Patients were recruited from local Grahamstown clinics. A pilot study to evaluate applicability of the instruments was conducted in 16 isiXhosa AIDS patients on ARVs and the results from this study informed further modifications to the instruments. One hundred and seventeen patients were recruited for the randomised control trial and were randomly allocated to either control group (who received standard care) or experimental group (who received standard care as well as pictogram medicine labels and the illustrated PIL). Interviews were conducted at baseline and at one, three and six months. Data were analysed statistically using the t-test, chi-squared test and ANOVA (Analysis of Variance) at a 5% level of significance. Correlations were determined using Pearson and Spearman rho correlations. Approval was obtained from Rhodes University Ethical Standards Committee, Settlers Hospital Ethics Committee and the Eastern Cape Department of Health. The results of this research showed that illustrated PILs and medicine labels enhanced understanding of HIV/AIDS and ARV information, resulting in a mean overall knowledge score in the experimental group of 96%, which was significantly higher than the 75% measured in the control group. Variable knowledge scores were measured in three areas: baseline knowledge of general HIV/AIDS-related information was good at 87%, whereas knowledge scores relating to ARV-related information (60%) and side-effects (52%) were lower. These scores improved significantly in the experimental group over the 4 interviews during the 6 month trial duration, whereas in the control group, they fluctuated only slightly around the original baseline score. There was no significant influence of gender on knowledge score, whereas health literacy, education level and age tested (at one and three months) had a significant influence on knowledge. Self-efficacy and adherence results were high, indicating that the patients have confidence in their ability to adhere to the ARV therapy and to practice optimal self-care. Age, gender and education, in most cases, significantly influenced self-efficacy, but were found to have no effect on adherence. The CD4 count improved over the trial duration which may have been influenced by a number of factors, including better knowledge of ARVs and improved adherence. No significant parametric correlation was found between knowledge score and change in CD4 count, however, Spearman's rho showed significance (rs=0.498; p=0.022). Both patients and healthcare providers were highly enthusiastic about the illustrated labels and PILs, and indicated their desire for such materials to be routinely available to public sector HIV/AIDS patients. The isiXhosa version of the PIL was preferred by all the patients. These simple, easy-to-read leaflets and illustrated medication labels were shown to increase understanding and knowledge of ARVs and HIV/AIDS in low-literate patients, and their availability in the first-language of the patients was central to making them a highly useful information source.
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- Authors: Barford, Kirsty-Lee
- Date: 2012
- Subjects: AIDS (Disease) -- Treatment -- South Africa , HIV infections -- Treatment -- South Africa , AIDS (Disease) -- Patients -- South Africa , HIV-positive persons -- South Africa , AIDS (Disease) -- Study and teaching -- South Africa , Antiretroviral agents -- South Africa , Communication in medicine -- South Africa , Communication in public health -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3863 , http://hdl.handle.net/10962/d1015678
- Description: South Africa has an estimated 920 000 patients on antiretrovirals (ARVs), the largest number of patients in any country. ARV therapy demands adherence levels in excess of 95% to avoid development of drug resistance, but adherence to ARV therapy is estimated to be only between 50% and 70%. Poor medication adherence is acknowledged as a major public health problem, reducing the effectiveness of therapy and promoting resistance to ARVs. More than two thirds of the South African population have marginal reading skills and this significantly influences a patient’s ability to read and understand health-related information. Patient education materials tailored for the South African population could be a useful aid in facilitating communication with patients and perhaps impact positively on their medicine-taking behaviour. This behaviour is influenced by patient knowledge, beliefs, attitudes and expectations and includes self-management, self-efficacy and adherence. Self-efficacy, which refers to patient confidence in the ability to self-manage medicine taking, is a key factor influencing adherence. This study aimed to develop illustrated patient information leaflets (PILs) and medicine labels for all first-line ARV regimens used in the public health sector in South Africa and, using a randomised control study design, to investigate the impact of these illustrated information materials on knowledge, medication-taking behaviours and health outcomes in HIV/AIDS patients taking ARVs. To achieve this aim, the objectives were to assess HIV/AIDS and ARV-related knowledge, as well as self-efficacy and adherence to ARV therapy; to assess the influence of demographic variables on knowledge, adherence and self-efficacy; to assess the influence of the information materials on knowledge, self-efficacy and adherence and to assess the association of knowledge with health outcomes. Medicine labels and PILs, both English and isiXhosa, were developed for ARV regimens 1a, 1b, 1c and 1d. The 8-item Morisky Medication Adherence Scale (MMAS-8) and HIV Treatment Adherence Self Efficacy Scale (HIV-ASES) instruments for measuring respectively adherence and self-efficacy, were modified to optimize clarity, simplicity and cultural acceptability and were translated into isiXhosa using a multi-stage translation-back translation. The questions and the rating scales, for both the MMAS and HIV-ASES, underwent preliminary qualitative evaluation in focus group discussions. Patients were recruited from local Grahamstown clinics. A pilot study to evaluate applicability of the instruments was conducted in 16 isiXhosa AIDS patients on ARVs and the results from this study informed further modifications to the instruments. One hundred and seventeen patients were recruited for the randomised control trial and were randomly allocated to either control group (who received standard care) or experimental group (who received standard care as well as pictogram medicine labels and the illustrated PIL). Interviews were conducted at baseline and at one, three and six months. Data were analysed statistically using the t-test, chi-squared test and ANOVA (Analysis of Variance) at a 5% level of significance. Correlations were determined using Pearson and Spearman rho correlations. Approval was obtained from Rhodes University Ethical Standards Committee, Settlers Hospital Ethics Committee and the Eastern Cape Department of Health. The results of this research showed that illustrated PILs and medicine labels enhanced understanding of HIV/AIDS and ARV information, resulting in a mean overall knowledge score in the experimental group of 96%, which was significantly higher than the 75% measured in the control group. Variable knowledge scores were measured in three areas: baseline knowledge of general HIV/AIDS-related information was good at 87%, whereas knowledge scores relating to ARV-related information (60%) and side-effects (52%) were lower. These scores improved significantly in the experimental group over the 4 interviews during the 6 month trial duration, whereas in the control group, they fluctuated only slightly around the original baseline score. There was no significant influence of gender on knowledge score, whereas health literacy, education level and age tested (at one and three months) had a significant influence on knowledge. Self-efficacy and adherence results were high, indicating that the patients have confidence in their ability to adhere to the ARV therapy and to practice optimal self-care. Age, gender and education, in most cases, significantly influenced self-efficacy, but were found to have no effect on adherence. The CD4 count improved over the trial duration which may have been influenced by a number of factors, including better knowledge of ARVs and improved adherence. No significant parametric correlation was found between knowledge score and change in CD4 count, however, Spearman's rho showed significance (rs=0.498; p=0.022). Both patients and healthcare providers were highly enthusiastic about the illustrated labels and PILs, and indicated their desire for such materials to be routinely available to public sector HIV/AIDS patients. The isiXhosa version of the PIL was preferred by all the patients. These simple, easy-to-read leaflets and illustrated medication labels were shown to increase understanding and knowledge of ARVs and HIV/AIDS in low-literate patients, and their availability in the first-language of the patients was central to making them a highly useful information source.
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