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:
- Date Issued: 2015
- 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:
- Date Issued: 2015
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:
- Date Issued: 2014
- 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:
- Date Issued: 2014
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:
- Date Issued: 2014
- 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:
- Date Issued: 2014
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:
- Date Issued: 2013
- 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:
- Date Issued: 2013
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:
- Date Issued: 2012
- 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:
- Date Issued: 2012
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.
- Full Text:
- Date Issued: 2012
- 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.
- Full Text:
- Date Issued: 2012
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.
- Full Text:
- Date Issued: 2012
- 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.
- Full Text:
- Date Issued: 2012
Monitoring and evaluation indicators of the HIV & AIDS programme in Grahamstown's public sector health care system
- Authors: Mahasele, Phehello Anthony
- Date: 2011
- Subjects: AIDS (Disease) -- Patients -- Services for -- South Africa -- Grahamstown -- Evaluation HIV-positive persons -- Services for -- South Africa -- Grahamstown -- Evaluation Public health -- South Africa -- Grahamstown -- Evaluation Antiretroviral agents -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3770 , http://hdl.handle.net/10962/d1003248
- Description: South Africa is one of the countries hardest hit with the Human Immunodeficiency Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) epidemic. In response to the epidemic, the South African government adopted the Comprehensive HIV & AIDS Care, Management and Treatment programme strategic plan (CCMT) in 2000 (1) and developed the Operational Plan for CCMT for antiretroviral therapy rollout in 2003 (2). In order to monitor the progress of the implementation of CCMT, the National Department of Health (NDOH) adopted the Monitoring and Evaluation (M & E) framework in 2004 (3). The aim of this study was to assess the HIV & AIDS programme in Grahamstown‘s public sector health care system by using the national M & E indicators of the HIV & AIDS programme. The national M & E framework was used as the data collection tool and available information was collected from various sources such as the District Health Office (DHO), Primary Health Care (PHC) office, accredited antiretroviral sites and the provincial pharmaceutical depot. Group interviews were conducted with key stakeholder health care professionals at the District Health Office, Primary Health Care office, Settlers Hospital and the provincial Department of Health personnel. A one-on-one interview was conducted with the Deputy Director of HIV & AIDS Directorate, monitoring and evaluation in the National Department of Health. Available indicators such as budget and expenditure including antiretroviral procurement; human resources; nutrition-related indicators; prevention care and treatment indicators were collected. A group interview was conducted to document current practices, or where there was a lack of documentation, for indicators such as traditional medicines and pharmacovigilance. Most of the national M & E indicators are not required to be collected or collated by the district because the reporting format designed by the provincial Department of Health is different. Facilities, districts and provinces in South Africa are at different levels of implementation of the antiretroviral programme and hence a common format of the M & E indicators is not used by all provinces. Uniform data collection is not achieved due to human resources‘ constraints and other challenges such as continued use of manual reporting systems by the clinics. Districts are expected to report according to the formats drawn up by the provincial Department of Health (DOH) and there is a lack of awareness regarding the national M & E document amongst the Grahamstown Health Care Professionals. There is a need for training on the use of the M & E national framework so that the HCPs at the primary and secondary levels of the health care system are proficient with the process of M & E, and can provide inputs as well as take ownership of the process. The establishment of an M & E unit in Grahamstown is essential so that data collection and submission of the HIV & AIDS programme in the public sector according to the National M & E framework is addressed. However, despite all constraints and challenges in the public sector health care system in Grahamstown, available human and financial resources are being used effectively to maintain the HIV & AIDS programme.
- Full Text:
- Date Issued: 2011
- Authors: Mahasele, Phehello Anthony
- Date: 2011
- Subjects: AIDS (Disease) -- Patients -- Services for -- South Africa -- Grahamstown -- Evaluation HIV-positive persons -- Services for -- South Africa -- Grahamstown -- Evaluation Public health -- South Africa -- Grahamstown -- Evaluation Antiretroviral agents -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3770 , http://hdl.handle.net/10962/d1003248
- Description: South Africa is one of the countries hardest hit with the Human Immunodeficiency Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) epidemic. In response to the epidemic, the South African government adopted the Comprehensive HIV & AIDS Care, Management and Treatment programme strategic plan (CCMT) in 2000 (1) and developed the Operational Plan for CCMT for antiretroviral therapy rollout in 2003 (2). In order to monitor the progress of the implementation of CCMT, the National Department of Health (NDOH) adopted the Monitoring and Evaluation (M & E) framework in 2004 (3). The aim of this study was to assess the HIV & AIDS programme in Grahamstown‘s public sector health care system by using the national M & E indicators of the HIV & AIDS programme. The national M & E framework was used as the data collection tool and available information was collected from various sources such as the District Health Office (DHO), Primary Health Care (PHC) office, accredited antiretroviral sites and the provincial pharmaceutical depot. Group interviews were conducted with key stakeholder health care professionals at the District Health Office, Primary Health Care office, Settlers Hospital and the provincial Department of Health personnel. A one-on-one interview was conducted with the Deputy Director of HIV & AIDS Directorate, monitoring and evaluation in the National Department of Health. Available indicators such as budget and expenditure including antiretroviral procurement; human resources; nutrition-related indicators; prevention care and treatment indicators were collected. A group interview was conducted to document current practices, or where there was a lack of documentation, for indicators such as traditional medicines and pharmacovigilance. Most of the national M & E indicators are not required to be collected or collated by the district because the reporting format designed by the provincial Department of Health is different. Facilities, districts and provinces in South Africa are at different levels of implementation of the antiretroviral programme and hence a common format of the M & E indicators is not used by all provinces. Uniform data collection is not achieved due to human resources‘ constraints and other challenges such as continued use of manual reporting systems by the clinics. Districts are expected to report according to the formats drawn up by the provincial Department of Health (DOH) and there is a lack of awareness regarding the national M & E document amongst the Grahamstown Health Care Professionals. There is a need for training on the use of the M & E national framework so that the HCPs at the primary and secondary levels of the health care system are proficient with the process of M & E, and can provide inputs as well as take ownership of the process. The establishment of an M & E unit in Grahamstown is essential so that data collection and submission of the HIV & AIDS programme in the public sector according to the National M & E framework is addressed. However, despite all constraints and challenges in the public sector health care system in Grahamstown, available human and financial resources are being used effectively to maintain the HIV & AIDS programme.
- Full Text:
- Date Issued: 2011
The impact of HAART on sexuality and medicine taking behaviours among people living with HIV/AIDS in Grahamstown
- Authors: Chizanga, Tongai Aldridge
- Date: 2010
- Subjects: AIDS (Disease) -- Treatment -- South Africa -- Grahamstown HIV infections -- Treatment -- South Africa -- Grahamstown Antiretroviral agents -- South Africa -- Grahamstown Patient compliance -- South Africa -- Grahamstown AIDS (Disease) -- Social aspects -- South Africa -- Grahamstown HIV infections -- Social aspects -- South Africa -- Grahamstown AIDS (Disease) -- Patients -- South Africa -- Grahamstown -- Sexual behavior HIV-positive persons -- South Africa -- Grahamstown -- Sexual behavior Patient education -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3750 , http://hdl.handle.net/10962/d1003228
- Description: Introduction: Adherence to Highly Active Antiretroviral Therapy (HAART) is critical for optimal therapeutic outcomes. A possible factor in adherence is the impact of HAART on sexual functioning. Methods: A mixed methods approach was used. A cohort of 14 people living with HIV/AIDS (PLWHA) in Grahamstown was identified. Two semi-structured interviews and two structured questionnaires were administered. In-depth interviews were conducted with two HIV counsellors in so as to obtain a different perspective on the topics. The theoretical framework used three health behaviour models: the Health Belief Model, Leventhal‘s Common-Sense Model of self regulation and the Transtheoretical model. Results: The participants were between 27 and 49 years old and had been on HAART for between 9 months and 10 years. Six participants were support staff members from Rhodes University and eight from the Raphael Centre – a local NGO which assists PLWHA.In most of the participants HAART was associated with increased libido and improved sexual functioning (sexual activity and sexual enjoyment). The use of alcohol increased risky sexual behaviour. Issues of adherence were seemingly not directly affected by the effects of HAART on sexuality. PLWHA, especially women, face challenges related to their sexuality, some of which are not directly related to their illness and treatment. The fear of transmitting drug resistant HIV or getting re-infected, stigma, disclosure issues,difficulties negotiating for safe sex among women, HAART-related lipodystrophic changes that affect one‘s sense of self and unmet reproductive needs are some of the problems that were reported. The men‘s dislike for condoms was overt and blatant. Discussion: Being diagnosed with HIV and reaching a point where treatment is requiredare life-changing events. Making decisions about one‘s life (including adherence to HAART, alcohol use and knowingly partaking in risky sexual encounters) become all the more significant in the context of AIDS. Intentional non-adherence is informed by the individual‘s assessment of the costs and benefits of taking treatment. Cultural influences,gendered power relations and misconceptions strongly influence sexual behaviours. Conclusion: The general lack of attention among health care providers concerning issues related to PLWHA‘s sexuality and reproductive issues needs to be addressed. Insights fromthe theoretical models should be integrated with empirical findings in designing adherence interventions.
- Full Text:
- Date Issued: 2010
- Authors: Chizanga, Tongai Aldridge
- Date: 2010
- Subjects: AIDS (Disease) -- Treatment -- South Africa -- Grahamstown HIV infections -- Treatment -- South Africa -- Grahamstown Antiretroviral agents -- South Africa -- Grahamstown Patient compliance -- South Africa -- Grahamstown AIDS (Disease) -- Social aspects -- South Africa -- Grahamstown HIV infections -- Social aspects -- South Africa -- Grahamstown AIDS (Disease) -- Patients -- South Africa -- Grahamstown -- Sexual behavior HIV-positive persons -- South Africa -- Grahamstown -- Sexual behavior Patient education -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3750 , http://hdl.handle.net/10962/d1003228
- Description: Introduction: Adherence to Highly Active Antiretroviral Therapy (HAART) is critical for optimal therapeutic outcomes. A possible factor in adherence is the impact of HAART on sexual functioning. Methods: A mixed methods approach was used. A cohort of 14 people living with HIV/AIDS (PLWHA) in Grahamstown was identified. Two semi-structured interviews and two structured questionnaires were administered. In-depth interviews were conducted with two HIV counsellors in so as to obtain a different perspective on the topics. The theoretical framework used three health behaviour models: the Health Belief Model, Leventhal‘s Common-Sense Model of self regulation and the Transtheoretical model. Results: The participants were between 27 and 49 years old and had been on HAART for between 9 months and 10 years. Six participants were support staff members from Rhodes University and eight from the Raphael Centre – a local NGO which assists PLWHA.In most of the participants HAART was associated with increased libido and improved sexual functioning (sexual activity and sexual enjoyment). The use of alcohol increased risky sexual behaviour. Issues of adherence were seemingly not directly affected by the effects of HAART on sexuality. PLWHA, especially women, face challenges related to their sexuality, some of which are not directly related to their illness and treatment. The fear of transmitting drug resistant HIV or getting re-infected, stigma, disclosure issues,difficulties negotiating for safe sex among women, HAART-related lipodystrophic changes that affect one‘s sense of self and unmet reproductive needs are some of the problems that were reported. The men‘s dislike for condoms was overt and blatant. Discussion: Being diagnosed with HIV and reaching a point where treatment is requiredare life-changing events. Making decisions about one‘s life (including adherence to HAART, alcohol use and knowingly partaking in risky sexual encounters) become all the more significant in the context of AIDS. Intentional non-adherence is informed by the individual‘s assessment of the costs and benefits of taking treatment. Cultural influences,gendered power relations and misconceptions strongly influence sexual behaviours. Conclusion: The general lack of attention among health care providers concerning issues related to PLWHA‘s sexuality and reproductive issues needs to be addressed. Insights fromthe theoretical models should be integrated with empirical findings in designing adherence interventions.
- Full Text:
- Date Issued: 2010
An illustrated information leaflet for low-literate HIV/AIDS patients on antiretroviral therapy : design, development and evaluation
- Authors: Ramela, Thato
- Date: 2009
- Subjects: Antiretroviral agents -- South Africa HIV-positive persons -- Care -- South Africa AIDS (Disease) -- Study and teaching -- South Africa HIV infections -- Treatment -- South Africa AIDS (Disease) -- Treatment -- South Africa AIDS (Disease) -- Africa, Sub-Saharan -- Statistics Communication in medicine -- South Africa Communication in public health -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3834 , http://hdl.handle.net/10962/d1007563
- Description: South Africa's HIV prevalence rate is estimated to be 5.7 million and at the end of2007 a total of 45845 HIV/AIDS adult patients were taking antiretroviral therapy (ART). The global incidence of HIV/AIDS has been slowly decreasing over the years but is still widespread. This disease is still more prevalent in sub-Saharan Africa than in other parts of the world, with more than 60% people living with HIV/AIDS. Highly active antiretroviral therapy (HAART), the treatment of choice, slows the progression of the human immunovirus but demands a high adherence rate in excess of 95%. Patients who are poorly informed about antiretrovirals (ARVs) and misunderstand medicine-taking instructions or experience unexpected side effects may interrupt therapy, predisposing them to the development of resistance. Such patients need information but, given the poor literacy skills prevalent in South Africa, written information is often not fully comprehended and is often written at too high a reading level. The objectives of this research project were to design, modify and evaluate HIV / AIDS patient education materials for low-literate isiXhosa speaking adults residing in Grahamstown and to examine their impact on the understanding of various aspects of the disease and its treatment. Pictograms illustrating common side effects of ARVs (e.g. stavudine, efavirenz, lamivudine), as well as various sources 'for purchasing nonprescription medicines, storage and medicine-taking instructions were designed and evaluated both qualitatively, using group discussions, and quantitatively through individual interviews where interpretation of the pictograms was assessed. These pictograms were incorporated in a patient information leaflet (PIL) which had been specifically designed for people with limited reading skills and was a simple document containing the minimum of essential text. A previously developed PIL was modified in collaboration with the target population and two versions were produced, one incorporating pictograms illustrating side effects, the other with none. Pictograms were used in both to illustrate other medicine-taking instructions. The PILs were tested objectively to assess the readability, format, content, and general design. They were translated into isiXhosa prior to being qualitatively and quantitatively evaluated in a low-literate isiXhosa speaking population. Understanding of the PILs was assessed by asking a series of questions about the PIL content. Participant opinion of the readability and appearance of the PIL was recorded. The relationship between PIL understanding and selected demographic variables was investigated. Findings from this study illustrated that well designed pictograms assist in the location of information in written leaflets and they may enhance understanding of the information. It was further demonstrated that education influences total understanding of PIL content thus emphasizing the need for tailor-written information in accordance with the education level of the target population. A desire to receive PILs incorporating pictograms was expressed by the majority of participants. Collaboration with the intended target population is essential to design culturally acceptable, easily interpreted pictograms and to produce user-friendly, easy-to-read, comprehensible patient education materials. The rigorous, iterative design, modification and testing process described in this study is one that should be adopted in producing all health-related education materials.
- Full Text:
- Date Issued: 2009
- Authors: Ramela, Thato
- Date: 2009
- Subjects: Antiretroviral agents -- South Africa HIV-positive persons -- Care -- South Africa AIDS (Disease) -- Study and teaching -- South Africa HIV infections -- Treatment -- South Africa AIDS (Disease) -- Treatment -- South Africa AIDS (Disease) -- Africa, Sub-Saharan -- Statistics Communication in medicine -- South Africa Communication in public health -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3834 , http://hdl.handle.net/10962/d1007563
- Description: South Africa's HIV prevalence rate is estimated to be 5.7 million and at the end of2007 a total of 45845 HIV/AIDS adult patients were taking antiretroviral therapy (ART). The global incidence of HIV/AIDS has been slowly decreasing over the years but is still widespread. This disease is still more prevalent in sub-Saharan Africa than in other parts of the world, with more than 60% people living with HIV/AIDS. Highly active antiretroviral therapy (HAART), the treatment of choice, slows the progression of the human immunovirus but demands a high adherence rate in excess of 95%. Patients who are poorly informed about antiretrovirals (ARVs) and misunderstand medicine-taking instructions or experience unexpected side effects may interrupt therapy, predisposing them to the development of resistance. Such patients need information but, given the poor literacy skills prevalent in South Africa, written information is often not fully comprehended and is often written at too high a reading level. The objectives of this research project were to design, modify and evaluate HIV / AIDS patient education materials for low-literate isiXhosa speaking adults residing in Grahamstown and to examine their impact on the understanding of various aspects of the disease and its treatment. Pictograms illustrating common side effects of ARVs (e.g. stavudine, efavirenz, lamivudine), as well as various sources 'for purchasing nonprescription medicines, storage and medicine-taking instructions were designed and evaluated both qualitatively, using group discussions, and quantitatively through individual interviews where interpretation of the pictograms was assessed. These pictograms were incorporated in a patient information leaflet (PIL) which had been specifically designed for people with limited reading skills and was a simple document containing the minimum of essential text. A previously developed PIL was modified in collaboration with the target population and two versions were produced, one incorporating pictograms illustrating side effects, the other with none. Pictograms were used in both to illustrate other medicine-taking instructions. The PILs were tested objectively to assess the readability, format, content, and general design. They were translated into isiXhosa prior to being qualitatively and quantitatively evaluated in a low-literate isiXhosa speaking population. Understanding of the PILs was assessed by asking a series of questions about the PIL content. Participant opinion of the readability and appearance of the PIL was recorded. The relationship between PIL understanding and selected demographic variables was investigated. Findings from this study illustrated that well designed pictograms assist in the location of information in written leaflets and they may enhance understanding of the information. It was further demonstrated that education influences total understanding of PIL content thus emphasizing the need for tailor-written information in accordance with the education level of the target population. A desire to receive PILs incorporating pictograms was expressed by the majority of participants. Collaboration with the intended target population is essential to design culturally acceptable, easily interpreted pictograms and to produce user-friendly, easy-to-read, comprehensible patient education materials. The rigorous, iterative design, modification and testing process described in this study is one that should be adopted in producing all health-related education materials.
- Full Text:
- Date Issued: 2009
Evaluation of the pharmaceutical availability of erythromycin from topical formulations
- Authors: Mandimika, Nyaradzo
- Date: 2008
- Subjects: Pharmacy -- Research Chromatographic analysis Gel permeation chromatography Gels (Pharmacy) Chemistry, analytic Acne -- Treatment Sebaceous glands -- Diseases -- Treatment Drugs -- Testing Erythromycin -- Bioavailability
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3771 , http://hdl.handle.net/10962/d1003249
- Description: Erythromycin (ERY) is a macrolide antibiotic which is used in the treatment of acne vulgaris.Acne is a common skin condition that occurs when the sebaceous glands and hair shafts become infected by the bacteria Propionibacterium acnes. Acne is a chronic condition that may last for years and the severity of the effects of the disease on patients is often undermined especially in third world countries where more emphasis is placed on other more life-threatening diseases. It may cause considerable physical and emotional distress to sufferers along with the possibility of permanent scarring. Although use of topical ERY formulations is not the first line of treatment it has proven to be effective in treating inflammation of skin and skin structures cause by the responsible bacteria. To-date there are a variety of vehicles which are used in preparing topical ERY formulations namely ointment and gel bases, alcoholic solutions and pledgets. All the gel formulations on the market contain hydroxypropyl cellulose, alcohol and water along with the active ingredient(s). However, some gel formulations contain propylene glycol in addition to these excipients an example being Emgel®. Propylene glycol has been shown to affect the penetration of topically applied drugs through the skin suggesting that it would be highly likely that those formulations which contain propylene glycol may release more ERY into the skin following application. With this in mind, two ERY gel formulations were produced which contained different percentages of propylene glycol. According to the FDA guidelines, pharmacokinetic measurements in blood, plasma and/or urine of topical dermatological drug products are not feasible to document bioequivalence since the active ingredient(s) in topical formulations is/are not intended to be absorbed into the systemic circulation and in addition, concentrations in extracutaneous biological tissues would generally not be measurable. This limits determination of bioavailability and assessment of bioequivalence of such products to pharmacodynamic measurements, clinical trials and dermatopharmacokinetic (DPK) measurements such as tape stripping (TS) and microdialysis (MD).TS is a sampling technique which involves sequential removal of layers of the stratum corneum using strips of adhesive tape. This technique has found increasing use in DPK studies for investigation of drug kinetics in the skin following the application of a topical formulation. The technique has also been used as a diagnostic tool in assessing the quality of the stratum corneum in diseased skin. In the current research study, the tape stripping technique was used to investigate the pharmaceutical/biological availability of topical gel formulations containing ERY. MD is another DPK sampling technique which has been used to determine the amount of a topically applied drug that penetrates through the stratum corneum to reach deeper tissues of the skin. The in vivo sampling technique involves the insertion of microdialysis probes beneath the skin surface in the dermal tissue and allows for real-time sampling of the analyte at its target site. Recently in vitro MD has also been successfully used to assess the pharmaceutical availability of a topical corticosteroid, mometesone furoate, from topical formulations. Based on this work, microdialysis was used to determine the pharmaceutical availability of ERY from gel formulations which were developed for use in this research. The results of the pharmaceutical availability of ERY from in vivo tape stripping studies and the in vitro microdialysis studies were compared to establish correlation between the data. Pharmaceutical equivalence and bioequivalence data obtained from the respective studies on the gel formulations were investigated by statistical analysis of the data generated from both the in vitro and in vivo experiments. In summary the objectives of this research were: 1. To develop and validate a high performance liquid chromatography method suitable to analyse ERY concentrations obtained from in vitro microdialysis studies and in vivo tape stripping studies. 2. To prepare two different ERY gel formulations with different percentage content of propylene glycol. 3. To determine the pharmaceutical availability of ERY from two different gel formulations using in vitro microdialysis. 4. To develop and validate a tape stripping technique which could be used to determine percutaneous penetration and bioequivalence of the gel formulations. 5. To compare in vitro microdialysis and in vivo tape stripping data and attempt to establish a correlation between the two different approaches.
- Full Text:
- Date Issued: 2008
- Authors: Mandimika, Nyaradzo
- Date: 2008
- Subjects: Pharmacy -- Research Chromatographic analysis Gel permeation chromatography Gels (Pharmacy) Chemistry, analytic Acne -- Treatment Sebaceous glands -- Diseases -- Treatment Drugs -- Testing Erythromycin -- Bioavailability
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3771 , http://hdl.handle.net/10962/d1003249
- Description: Erythromycin (ERY) is a macrolide antibiotic which is used in the treatment of acne vulgaris.Acne is a common skin condition that occurs when the sebaceous glands and hair shafts become infected by the bacteria Propionibacterium acnes. Acne is a chronic condition that may last for years and the severity of the effects of the disease on patients is often undermined especially in third world countries where more emphasis is placed on other more life-threatening diseases. It may cause considerable physical and emotional distress to sufferers along with the possibility of permanent scarring. Although use of topical ERY formulations is not the first line of treatment it has proven to be effective in treating inflammation of skin and skin structures cause by the responsible bacteria. To-date there are a variety of vehicles which are used in preparing topical ERY formulations namely ointment and gel bases, alcoholic solutions and pledgets. All the gel formulations on the market contain hydroxypropyl cellulose, alcohol and water along with the active ingredient(s). However, some gel formulations contain propylene glycol in addition to these excipients an example being Emgel®. Propylene glycol has been shown to affect the penetration of topically applied drugs through the skin suggesting that it would be highly likely that those formulations which contain propylene glycol may release more ERY into the skin following application. With this in mind, two ERY gel formulations were produced which contained different percentages of propylene glycol. According to the FDA guidelines, pharmacokinetic measurements in blood, plasma and/or urine of topical dermatological drug products are not feasible to document bioequivalence since the active ingredient(s) in topical formulations is/are not intended to be absorbed into the systemic circulation and in addition, concentrations in extracutaneous biological tissues would generally not be measurable. This limits determination of bioavailability and assessment of bioequivalence of such products to pharmacodynamic measurements, clinical trials and dermatopharmacokinetic (DPK) measurements such as tape stripping (TS) and microdialysis (MD).TS is a sampling technique which involves sequential removal of layers of the stratum corneum using strips of adhesive tape. This technique has found increasing use in DPK studies for investigation of drug kinetics in the skin following the application of a topical formulation. The technique has also been used as a diagnostic tool in assessing the quality of the stratum corneum in diseased skin. In the current research study, the tape stripping technique was used to investigate the pharmaceutical/biological availability of topical gel formulations containing ERY. MD is another DPK sampling technique which has been used to determine the amount of a topically applied drug that penetrates through the stratum corneum to reach deeper tissues of the skin. The in vivo sampling technique involves the insertion of microdialysis probes beneath the skin surface in the dermal tissue and allows for real-time sampling of the analyte at its target site. Recently in vitro MD has also been successfully used to assess the pharmaceutical availability of a topical corticosteroid, mometesone furoate, from topical formulations. Based on this work, microdialysis was used to determine the pharmaceutical availability of ERY from gel formulations which were developed for use in this research. The results of the pharmaceutical availability of ERY from in vivo tape stripping studies and the in vitro microdialysis studies were compared to establish correlation between the data. Pharmaceutical equivalence and bioequivalence data obtained from the respective studies on the gel formulations were investigated by statistical analysis of the data generated from both the in vitro and in vivo experiments. In summary the objectives of this research were: 1. To develop and validate a high performance liquid chromatography method suitable to analyse ERY concentrations obtained from in vitro microdialysis studies and in vivo tape stripping studies. 2. To prepare two different ERY gel formulations with different percentage content of propylene glycol. 3. To determine the pharmaceutical availability of ERY from two different gel formulations using in vitro microdialysis. 4. To develop and validate a tape stripping technique which could be used to determine percutaneous penetration and bioequivalence of the gel formulations. 5. To compare in vitro microdialysis and in vivo tape stripping data and attempt to establish a correlation between the two different approaches.
- Full Text:
- Date Issued: 2008
Neuroprotective mechanisms of nevirapine and efavirenz in a model of neurodegeneration
- Authors: Zheve, Georgina Teurai
- Date: 2008
- Subjects: HIV infections -- Treatment AIDS (Disease) -- Treatment AIDS dementia complex -- Treatment Nervous system -- Degeneration -- Treatment Melatonin Neurotoxic agents Quinolinic acid
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3807 , http://hdl.handle.net/10962/d1003285
- Description: AIDS Dementia Complex (ADC) is a neurodegenerative disorder implicated in HIV-1 infection that is associated with elevated levels of the neurotoxin, quinolinic acid (QA) which causes a cascade of events to occur, leading to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. In clinical studies, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP) have been shown to potentially delay the progressive degeneration of neurons, thus reducing the frequency and neurological deficits associated with ADC. Despite these neuroprotective implications, there is still no biochemical data to demonstrate the mechanisms through which these agents offer neuroprotection. The present study aims to elucidate and further characterize the possible antioxidant and neuroprotective mechanisms of NVP and EFV in vitro and in vivo, using QA-induced neurotoxicity as a model. Research has demonstrated that antioxidants and metal chelators have the ability to offer neuroprotection against free radical induced injury and may be beneficial in the prevention or treatment of neurodegeneration. Hence the antioxidant and metal binding properties of these agents were investigated respectively. Inorganic studies, including the 1, 1-diphenyl-2 picrylhydrazyl (DPPH) assay, show that these agents readily scavenge free radicals in vitro, thus postulating the antioxidant property of these agents. The enhancement of superoxide radical generation and iron mediated Fenton reaction by QA is related to lipid peroxidation in biological systems, the extent of which was assayed using the nitroblue tetrazolium and thiobarbituric acid method respectively. Both agents significantly curtail QA-induced lipid peroxidation and potentially scavenge superoxide anions generated by cyanide in vitro. Furthermore, in vivo results demonstrate the ability of NVP and EFV to protect hippocampal neurons against lipid peroxidation induced by QA and superoxide radicals generated as a consequence thereof. The alleviation of QA-induced oxidative stress in vitro possibly occurs through the binding of iron (II) and / or iron (III), and this argument is further strengthened by the ability of EFV and not NVP to reduce iron (II)-induced lipid peroxidation in vitro directly. In addition the ferrozine and electrochemistry assay were used to measure the extent of iron (II) Fe[superscript 2+] and iron (III) Fe[superscript 3+] chelation activity. Both assays demonstrate that these agents bind iron (II) and iron (III), and prevent redox recycling of iron and subsequent complexation of Fe[superscript 2+] with QA which enhances neuronal damage. Both NNRTIs inhibit the endogenous biosynthesis of QA by inhibiting liver tryptophan 2, 3-dioxygenase activity in vivo and subsequently increasing hippocampal serotonin levels. Furthermore, these agents reduce the turnover of hippocampal serotonin to 5-hydroxyindole acetic acid. NVP and not EFV increase 5-hydroxyindole acetic acid and norepinephrine levels in the hippocampus. The results of the pineal indole metabolism study show that NVP increases the synthesis of melatonin, but decreases N-acetylserotonin, 5-hydroxyindole acetic acid and 5-hydroxytryptophol levels. Furthermore, it shows that EFV decreases 5-hydroxyindole acetic acid and melatonin synthesis. Behavioural studies using a Morris water maze show that the post-treatment of rats with NVP and EFV significantly improves QA-induced spatial memory deficits in the hippocampus. This study therefore provides novel information regarding the neuroprotective mechanisms of NVP and EFV. These findings strengthen the argument that these NNRTIs not only have antiviral effects but possess potential neuroprotective properties, which may contribute to the effectiveness of these drugs in the treatment of ADC.
- Full Text:
- Date Issued: 2008
- Authors: Zheve, Georgina Teurai
- Date: 2008
- Subjects: HIV infections -- Treatment AIDS (Disease) -- Treatment AIDS dementia complex -- Treatment Nervous system -- Degeneration -- Treatment Melatonin Neurotoxic agents Quinolinic acid
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3807 , http://hdl.handle.net/10962/d1003285
- Description: AIDS Dementia Complex (ADC) is a neurodegenerative disorder implicated in HIV-1 infection that is associated with elevated levels of the neurotoxin, quinolinic acid (QA) which causes a cascade of events to occur, leading to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. In clinical studies, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP) have been shown to potentially delay the progressive degeneration of neurons, thus reducing the frequency and neurological deficits associated with ADC. Despite these neuroprotective implications, there is still no biochemical data to demonstrate the mechanisms through which these agents offer neuroprotection. The present study aims to elucidate and further characterize the possible antioxidant and neuroprotective mechanisms of NVP and EFV in vitro and in vivo, using QA-induced neurotoxicity as a model. Research has demonstrated that antioxidants and metal chelators have the ability to offer neuroprotection against free radical induced injury and may be beneficial in the prevention or treatment of neurodegeneration. Hence the antioxidant and metal binding properties of these agents were investigated respectively. Inorganic studies, including the 1, 1-diphenyl-2 picrylhydrazyl (DPPH) assay, show that these agents readily scavenge free radicals in vitro, thus postulating the antioxidant property of these agents. The enhancement of superoxide radical generation and iron mediated Fenton reaction by QA is related to lipid peroxidation in biological systems, the extent of which was assayed using the nitroblue tetrazolium and thiobarbituric acid method respectively. Both agents significantly curtail QA-induced lipid peroxidation and potentially scavenge superoxide anions generated by cyanide in vitro. Furthermore, in vivo results demonstrate the ability of NVP and EFV to protect hippocampal neurons against lipid peroxidation induced by QA and superoxide radicals generated as a consequence thereof. The alleviation of QA-induced oxidative stress in vitro possibly occurs through the binding of iron (II) and / or iron (III), and this argument is further strengthened by the ability of EFV and not NVP to reduce iron (II)-induced lipid peroxidation in vitro directly. In addition the ferrozine and electrochemistry assay were used to measure the extent of iron (II) Fe[superscript 2+] and iron (III) Fe[superscript 3+] chelation activity. Both assays demonstrate that these agents bind iron (II) and iron (III), and prevent redox recycling of iron and subsequent complexation of Fe[superscript 2+] with QA which enhances neuronal damage. Both NNRTIs inhibit the endogenous biosynthesis of QA by inhibiting liver tryptophan 2, 3-dioxygenase activity in vivo and subsequently increasing hippocampal serotonin levels. Furthermore, these agents reduce the turnover of hippocampal serotonin to 5-hydroxyindole acetic acid. NVP and not EFV increase 5-hydroxyindole acetic acid and norepinephrine levels in the hippocampus. The results of the pineal indole metabolism study show that NVP increases the synthesis of melatonin, but decreases N-acetylserotonin, 5-hydroxyindole acetic acid and 5-hydroxytryptophol levels. Furthermore, it shows that EFV decreases 5-hydroxyindole acetic acid and melatonin synthesis. Behavioural studies using a Morris water maze show that the post-treatment of rats with NVP and EFV significantly improves QA-induced spatial memory deficits in the hippocampus. This study therefore provides novel information regarding the neuroprotective mechanisms of NVP and EFV. These findings strengthen the argument that these NNRTIs not only have antiviral effects but possess potential neuroprotective properties, which may contribute to the effectiveness of these drugs in the treatment of ADC.
- Full Text:
- Date Issued: 2008
Development and in vitro evaluation of a clobetasol 17-propionate topical cream formulation
- Authors: Wa Kasongo, Kasongo
- Date: 2007
- Subjects: Adrenocortical hormones , Adrenocortical hormones -- Physiological effect , Drugs -- Testing , Drug development , Dermatopharmacology
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3799 , http://hdl.handle.net/10962/d1003277 , Adrenocortical hormones , Adrenocortical hormones -- Physiological effect , Drugs -- Testing , Drug development , Dermatopharmacology
- Description: One of the primary contributing factors to the escalating costs of health care is the high cost of innovator pharmaceutical products. As a consequence, health authorities in various countries and in particular in the developing world have identified generic prescribing and generic substitution as possible strategies to contain the escalating costs of health care provision. There is therefore a need for formulation scientists in developing countries to invest more time in the research and development of generic formulations. Clobetasol 17-propionate (CP) generic cream formulations containing 0.05% w/w of the drug were manufactured and characterized using in vitro testing. Formulation development studies were preceded by the development and validation of an RP-HPLC with UV detection for the quantitation and characterization of CP in innovator and generic cream formulations during formulation development and assessment studies. Furthermore the in vitro release ates of CP release from innovator and generic cream formulations were monitored using a validated in vitro release test method developed in these studies. The formulation of CP cream products was accomplished using a variety of commercially available mixed primary emulsifiers, such as Estol® 1474, Ritapro® 200, Emulcire® 61 WL and Gelot® 64. Successful formulations were selected based on their ability to remain physically stable immediately after manufacture and for 24 hours after storage at room temperature (22°C). Estol® 1474 was found to produce an unstable cream and was therefore not investigated further. The other three emulgents produced stable creams, but only the in vitro release profile of CP from a cream manufactured to contain Gelot® 64 was found to be statistically similar to that of the innovator formulation. Therefore the cream containing Gelot® 64 was selected as the most appropriate prototype generic cream formulation and was characterized in vitro in terms of CP content, viscosity, pH and in vitro release rate. Data generated from these studies were compared to those of the innovator product, Dermovate® cream, using statistical methods. The CP content, pH and in vitro release rate data of the CP formulation were similar to those of the innovator product, however the intrinsic viscosity of Dermovate® cream was almost three (3) times greater than the intrinsic viscosity of the test formulation developed using Gelot® 64. The CP cream formulation developed in these studies was stored for 4 weeks at 40 ± 2°C and 25 ± 5% RH in an incubator and the formulation was found to be stable. A formulation has been developed and assessed and found to be suitable for use as a topical semi-solid dosage form for CP.
- Full Text:
- Date Issued: 2007
- Authors: Wa Kasongo, Kasongo
- Date: 2007
- Subjects: Adrenocortical hormones , Adrenocortical hormones -- Physiological effect , Drugs -- Testing , Drug development , Dermatopharmacology
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3799 , http://hdl.handle.net/10962/d1003277 , Adrenocortical hormones , Adrenocortical hormones -- Physiological effect , Drugs -- Testing , Drug development , Dermatopharmacology
- Description: One of the primary contributing factors to the escalating costs of health care is the high cost of innovator pharmaceutical products. As a consequence, health authorities in various countries and in particular in the developing world have identified generic prescribing and generic substitution as possible strategies to contain the escalating costs of health care provision. There is therefore a need for formulation scientists in developing countries to invest more time in the research and development of generic formulations. Clobetasol 17-propionate (CP) generic cream formulations containing 0.05% w/w of the drug were manufactured and characterized using in vitro testing. Formulation development studies were preceded by the development and validation of an RP-HPLC with UV detection for the quantitation and characterization of CP in innovator and generic cream formulations during formulation development and assessment studies. Furthermore the in vitro release ates of CP release from innovator and generic cream formulations were monitored using a validated in vitro release test method developed in these studies. The formulation of CP cream products was accomplished using a variety of commercially available mixed primary emulsifiers, such as Estol® 1474, Ritapro® 200, Emulcire® 61 WL and Gelot® 64. Successful formulations were selected based on their ability to remain physically stable immediately after manufacture and for 24 hours after storage at room temperature (22°C). Estol® 1474 was found to produce an unstable cream and was therefore not investigated further. The other three emulgents produced stable creams, but only the in vitro release profile of CP from a cream manufactured to contain Gelot® 64 was found to be statistically similar to that of the innovator formulation. Therefore the cream containing Gelot® 64 was selected as the most appropriate prototype generic cream formulation and was characterized in vitro in terms of CP content, viscosity, pH and in vitro release rate. Data generated from these studies were compared to those of the innovator product, Dermovate® cream, using statistical methods. The CP content, pH and in vitro release rate data of the CP formulation were similar to those of the innovator product, however the intrinsic viscosity of Dermovate® cream was almost three (3) times greater than the intrinsic viscosity of the test formulation developed using Gelot® 64. The CP cream formulation developed in these studies was stored for 4 weeks at 40 ± 2°C and 25 ± 5% RH in an incubator and the formulation was found to be stable. A formulation has been developed and assessed and found to be suitable for use as a topical semi-solid dosage form for CP.
- Full Text:
- Date Issued: 2007
Competing interests and change within the pharmacy education system in South Africa
- Authors: Allan, Lucie
- Date: 2006
- Subjects: Pharmacy -- South Africa Pharmacy -- Study and teaching -- South Africa Pharmacy -- Practice -- South Africa Community pharmacy services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3741 , http://hdl.handle.net/10962/d1003219
- Description: This thesis provides a historical account of the emergence of the pharmacy education system in South Africa, and an analysis of the influence of competing interest groups over the pharmacy education curriculum. It provides a critical evaluation of structural-consensus and micro-interpretive approaches to medical and pharmacy education, and sets out a macrointerpretive account of pharmacy education in South Africa. Following Margaret Archer (1979) it analyzes three forms of negotiation between competing interest groups in their efforts to change the pharmacy curriculum; these are political manipulation, external transaction and internal initiation. The thesis argues that whilst the private sector interest group (comprising of retail, wholesale and manufacturing pharmacy) dominated the pharmacy education system until 1994, since then a newly emerged government interest group has begun to compete for educational control. The priorities pursued by this interest group have consistently reflected the objectives set out in the ANC National Health Plan of 1994. The thesis maintains that given its frustration over the non-implementation of the ANC’s health policy objectives, the government interest group is likely to resort to direct political manipulation by passing legislation to alter the content of the current pharmacy curriculum. Such changes would seek to ensure that the syllabus more accurately reflects the ANC Plan’s community health and primary health care objectives. The thesis asserts that such an outcome (of direct political manipulation of the curriculum) is not inevitable, and can be avoided through a process of internally initiated change. It presents the findings of an interpretive case study into how the Rhodes University Community Experience Programme (CEP) influenced final year pharmacy students’ perceptions of the role of the pharmacist. The students’ comments were collected by means of focus group interviews, participant observation and documentary analysis. Whilst the CEP did not successfully transform their concept of the pharmacist’s role, it did succeed in influencing students’ understanding of the notions of community pharmacy and primary health care in line with the government interest group’s health objectives. This thesis concludes that internally initiated change within the pharmacy education system, would be preferable to that imposed through external political manipulation, as such change would be more likely to preserve the independent professional interests of pharmacy academics.
- Full Text:
- Date Issued: 2006
- Authors: Allan, Lucie
- Date: 2006
- Subjects: Pharmacy -- South Africa Pharmacy -- Study and teaching -- South Africa Pharmacy -- Practice -- South Africa Community pharmacy services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3741 , http://hdl.handle.net/10962/d1003219
- Description: This thesis provides a historical account of the emergence of the pharmacy education system in South Africa, and an analysis of the influence of competing interest groups over the pharmacy education curriculum. It provides a critical evaluation of structural-consensus and micro-interpretive approaches to medical and pharmacy education, and sets out a macrointerpretive account of pharmacy education in South Africa. Following Margaret Archer (1979) it analyzes three forms of negotiation between competing interest groups in their efforts to change the pharmacy curriculum; these are political manipulation, external transaction and internal initiation. The thesis argues that whilst the private sector interest group (comprising of retail, wholesale and manufacturing pharmacy) dominated the pharmacy education system until 1994, since then a newly emerged government interest group has begun to compete for educational control. The priorities pursued by this interest group have consistently reflected the objectives set out in the ANC National Health Plan of 1994. The thesis maintains that given its frustration over the non-implementation of the ANC’s health policy objectives, the government interest group is likely to resort to direct political manipulation by passing legislation to alter the content of the current pharmacy curriculum. Such changes would seek to ensure that the syllabus more accurately reflects the ANC Plan’s community health and primary health care objectives. The thesis asserts that such an outcome (of direct political manipulation of the curriculum) is not inevitable, and can be avoided through a process of internally initiated change. It presents the findings of an interpretive case study into how the Rhodes University Community Experience Programme (CEP) influenced final year pharmacy students’ perceptions of the role of the pharmacist. The students’ comments were collected by means of focus group interviews, participant observation and documentary analysis. Whilst the CEP did not successfully transform their concept of the pharmacist’s role, it did succeed in influencing students’ understanding of the notions of community pharmacy and primary health care in line with the government interest group’s health objectives. This thesis concludes that internally initiated change within the pharmacy education system, would be preferable to that imposed through external political manipulation, as such change would be more likely to preserve the independent professional interests of pharmacy academics.
- Full Text:
- Date Issued: 2006
Patient education : the effect on patient behaviour
- Authors: Shiri, Clarris
- Date: 2006
- Subjects: Patient education -- South Africa -- Eastern Cape Patient compliance -- South Africa -- Eastern Cape Hypertension -- Treatment -- South Africa Health care services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3790 , http://hdl.handle.net/10962/d1003268
- Description: Evidence suggests that the prevalence of certain non-communicable diseases, such as hypertension, is increasing rapidly, and that patients with these diseases are making significant demands on the health services of the nations in sub-Saharan Africa. However, these countries also face other health-related challenges such as communicable diseases and underdevelopmentrelated diseases. Developing countries like South Africa have limited resources, in terms of man power and financial capital, to address the challenges that they are facing. Non-communicable diseases cannot be ignored and since health care providers cannot meet the challenges, it is worthwhile to empower patients to be involved in the management of their conditions. Patient education is a tool that can be used to enable patients to manage their chronic conditions and thereby reduce the morbidity and mortality rates of these conditions. The aim of this study was to investigate the effect of a patient education intervention on participants’ levels of knowledge about hypertension and its therapy, beliefs about medicines and adherence to anti-hypertensive therapy. The intervention consisted of talks and discussions with all the participants as one group and as individuals. There was also written information given to the participants. Their levels of knowledge about hypertension and its therapy were measured using one-on-one interviews and self-administered questionnaires. Beliefs about medicines were measured using the Beliefs about Medicines Questionnaire (BMQ) whilst adherence levels were measured using pill counts, elf-reports and prescription refill records. The participants’ blood pressure readings and body mass indices were also recorded throughout the study. The parameters before and after the educational intervention were compared using statistical analyses. The participants’ levels of knowledge about hypertension and its therapy significantly increased whilst their beliefs about medicines were positively modified after the educational intervention. There were also increases, though not statistically significant, in the participants’ levels of adherence to anti-hypertensive therapy. Unexpectedly, the blood pressure readings and body mass indices increased significantly. The participants gave positive feedback regarding the educational intervention and indicated a desire for similar programmes to be run continuously. They also suggested that such programmes be implemented for other common chronic conditions such as asthma and diabetes. This study proved that patient education programmes can be implemented to modify patients’ levels of knowledge about their conditions and the therapy, beliefs about medicines and adherence to therapy. However, such programmes need to be conducted over a long period of time since changes involving behaviour take a long time.
- Full Text:
- Date Issued: 2006
- Authors: Shiri, Clarris
- Date: 2006
- Subjects: Patient education -- South Africa -- Eastern Cape Patient compliance -- South Africa -- Eastern Cape Hypertension -- Treatment -- South Africa Health care services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3790 , http://hdl.handle.net/10962/d1003268
- Description: Evidence suggests that the prevalence of certain non-communicable diseases, such as hypertension, is increasing rapidly, and that patients with these diseases are making significant demands on the health services of the nations in sub-Saharan Africa. However, these countries also face other health-related challenges such as communicable diseases and underdevelopmentrelated diseases. Developing countries like South Africa have limited resources, in terms of man power and financial capital, to address the challenges that they are facing. Non-communicable diseases cannot be ignored and since health care providers cannot meet the challenges, it is worthwhile to empower patients to be involved in the management of their conditions. Patient education is a tool that can be used to enable patients to manage their chronic conditions and thereby reduce the morbidity and mortality rates of these conditions. The aim of this study was to investigate the effect of a patient education intervention on participants’ levels of knowledge about hypertension and its therapy, beliefs about medicines and adherence to anti-hypertensive therapy. The intervention consisted of talks and discussions with all the participants as one group and as individuals. There was also written information given to the participants. Their levels of knowledge about hypertension and its therapy were measured using one-on-one interviews and self-administered questionnaires. Beliefs about medicines were measured using the Beliefs about Medicines Questionnaire (BMQ) whilst adherence levels were measured using pill counts, elf-reports and prescription refill records. The participants’ blood pressure readings and body mass indices were also recorded throughout the study. The parameters before and after the educational intervention were compared using statistical analyses. The participants’ levels of knowledge about hypertension and its therapy significantly increased whilst their beliefs about medicines were positively modified after the educational intervention. There were also increases, though not statistically significant, in the participants’ levels of adherence to anti-hypertensive therapy. Unexpectedly, the blood pressure readings and body mass indices increased significantly. The participants gave positive feedback regarding the educational intervention and indicated a desire for similar programmes to be run continuously. They also suggested that such programmes be implemented for other common chronic conditions such as asthma and diabetes. This study proved that patient education programmes can be implemented to modify patients’ levels of knowledge about their conditions and the therapy, beliefs about medicines and adherence to therapy. However, such programmes need to be conducted over a long period of time since changes involving behaviour take a long time.
- Full Text:
- Date Issued: 2006
The natural product chemistry of South African Plocamium species
- Authors: Knott, Michael George
- Date: 2003
- Subjects: Marine algae -- South Africa Red algae -- South Africa Green algae -- South Africa Halimeda -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3820 , http://hdl.handle.net/10962/d1004920
- Description: The brine shrimp lethality assay was used as a preliminary tool to screen eighteen seaweeds collected from the South African coast. Of the seaweeds tested, the red algae Plocamium corallorhiza and Hypnea rosea, and the green alga Halimeda sp., showed the most potent activity. The chemical investigation of P. corallorhiza resulted in the isolation and structural elucidation of five previously undescribed secondary metabolites, along with three known compounds and four possible artifacts of the extraction process. Standard spectroscopic methods and comparison with known compounds were used to determine the structures of the new metabolites. The new compounds included the linear halogenated monoterpenes 4,8-dibromo-1, 1-dichloro-3,7-dimethyl-2,6-octadiene (99), 4,6-dibromo-l, 1-dichloro-3,7-dimethyl-2,7-octadiene (100), 4,8-dibromo-l, 1,7-trichloro-3,7-dimethyl-2,5-octadiene (101) and 3,4,6,7-tetrachloro-3,7-dimethyl-l-octene (102) and the cyclic monoterpene 5-bromo-5-bromomethyl-I-chlorovinyl-2,4-dichloro-methylcyclohexane (103) while the known compounds were identified as 4-bromo-5-bromomethyl-1chlorovinyl-2,5-dichloro-methylcyclohexane (35), 1,4,8-tribromo-3, 7 -dichloro-3,7-dimethyl-1,5-octadiene (94) and 8-bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5-octadiene (96). The four methoxylated compounds (104-107) were presumably formed via a standard substitution reaction between the halogenated monoterpenes 96 and 101 and MeOH, which was used as a component in the extraction solvent. With over 100 000 natural products having been reported, it has become necessary to employ an efficient dereplication strategy to quickly identify known compounds. A simple Gas Chromatography-Mass Spectrometry (GC-MS) method for the efficient physicochemical screening, identification and dereplication of Plocamium metabolites was developed. In this study the crude extracts of P. corallorhiza, P. cornutum and P. maxillosum were screened by GC-MS and the retention times and mass spectral fragmentation patterns of compounds 94, 96, 99 - 107 were used to quickly identify known and new compounds in the crude extracts of P. cornutum and P. maxillosum. This data indicated that compounds 99, 100, 103 were present in both P. corallorhiza and P.cornutum, while compound 102 was found to be present in P. corallorhiza, P. cornutum and P. maxillosum. These studies also indicated that ecotypes and chemotypes are not a significant feature of P. corallorhiza and P. cornutum. Different species of Plocamium (namely: P. corallorhiza, P. cornutum, and P. maxillosum) have very different chemical profiles, and GC may therefore have appreciable taxonomic application in the identification of the different Plocamium spp. which are endemic to South Africa.
- Full Text:
- Date Issued: 2003
- Authors: Knott, Michael George
- Date: 2003
- Subjects: Marine algae -- South Africa Red algae -- South Africa Green algae -- South Africa Halimeda -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3820 , http://hdl.handle.net/10962/d1004920
- Description: The brine shrimp lethality assay was used as a preliminary tool to screen eighteen seaweeds collected from the South African coast. Of the seaweeds tested, the red algae Plocamium corallorhiza and Hypnea rosea, and the green alga Halimeda sp., showed the most potent activity. The chemical investigation of P. corallorhiza resulted in the isolation and structural elucidation of five previously undescribed secondary metabolites, along with three known compounds and four possible artifacts of the extraction process. Standard spectroscopic methods and comparison with known compounds were used to determine the structures of the new metabolites. The new compounds included the linear halogenated monoterpenes 4,8-dibromo-1, 1-dichloro-3,7-dimethyl-2,6-octadiene (99), 4,6-dibromo-l, 1-dichloro-3,7-dimethyl-2,7-octadiene (100), 4,8-dibromo-l, 1,7-trichloro-3,7-dimethyl-2,5-octadiene (101) and 3,4,6,7-tetrachloro-3,7-dimethyl-l-octene (102) and the cyclic monoterpene 5-bromo-5-bromomethyl-I-chlorovinyl-2,4-dichloro-methylcyclohexane (103) while the known compounds were identified as 4-bromo-5-bromomethyl-1chlorovinyl-2,5-dichloro-methylcyclohexane (35), 1,4,8-tribromo-3, 7 -dichloro-3,7-dimethyl-1,5-octadiene (94) and 8-bromo-1,3,4,7-tetrachloro-3,7-dimethyl-1,5-octadiene (96). The four methoxylated compounds (104-107) were presumably formed via a standard substitution reaction between the halogenated monoterpenes 96 and 101 and MeOH, which was used as a component in the extraction solvent. With over 100 000 natural products having been reported, it has become necessary to employ an efficient dereplication strategy to quickly identify known compounds. A simple Gas Chromatography-Mass Spectrometry (GC-MS) method for the efficient physicochemical screening, identification and dereplication of Plocamium metabolites was developed. In this study the crude extracts of P. corallorhiza, P. cornutum and P. maxillosum were screened by GC-MS and the retention times and mass spectral fragmentation patterns of compounds 94, 96, 99 - 107 were used to quickly identify known and new compounds in the crude extracts of P. cornutum and P. maxillosum. This data indicated that compounds 99, 100, 103 were present in both P. corallorhiza and P.cornutum, while compound 102 was found to be present in P. corallorhiza, P. cornutum and P. maxillosum. These studies also indicated that ecotypes and chemotypes are not a significant feature of P. corallorhiza and P. cornutum. Different species of Plocamium (namely: P. corallorhiza, P. cornutum, and P. maxillosum) have very different chemical profiles, and GC may therefore have appreciable taxonomic application in the identification of the different Plocamium spp. which are endemic to South Africa.
- Full Text:
- Date Issued: 2003