A drug utilisation review of lithium at a public sector psychiatric hospital
- Authors: Mapfumo, Charlotte
- Date: 2020-04
- Subjects: Lithium -- Therapeutic use , Psychiatric hospitals -- South Africa -- Grahamstown , Drug utilization , Psychiatric hospital care , Manic-depressive illness , Lithium -- Toxicology , Drug monitoring
- Language: English
- Type: text , Thesis , Masters , M.Pharm
- Identifier: http://hdl.handle.net/10962/150541 , vital:38983
- Description: Bipolar disorder (BD) is a common mental condition that affects about 60 million people globally. Lithium is among the drugs of choice used to treat BD and other affective disorders such as schizoaffective disorder (SD). Lithium is a mood stabiliser with antimanic, antidepressant and anti-suicidal properties. Lithium has complex mechanisms of action and a narrow therapeutic index (NTI). Therapeutic drug monitoring (TDM) is a vital component of lithium therapy due to its NTI. Lithium toxicity can occur at therapeutic levels and is characterised by symptoms such as blurred vision and convulsions. Lithium interacts with a number of drugs resulting in lithium toxicity or diminished effects of lithium. Symptoms of lithium toxicity range from abdominal pain, convulsions and death. Lithium use is associated with serious adverse effects on renal and thyroid function. Other adverse effects include tremor and weight gain. Monitoring of lithium serum levels, renal and thyroid function are therefore recommended for patients on lithium therapy. Monitoring of these parameters assists in the early detection of any problems associated with lithium use. The metabolic monitoring of lithium is vital due to the adverse effect profile of lithium and the current South African Standard Treatment Guidelines Hospital level: Adults, do not have any recommendations for the monitoring of metabolic parameters. The National Institute for Health and Care Excellence (NICE) may be used and adapted for the South African setting. Aim and Objectives: The general aim of the study was to conduct a drug utilisation review (DUR) on lithium through investigating its prescribing and monitoring patterns in both inpatients and outpatients at Fort England Hospital. Methodology: The study was in the form of a retrospective DUR. Data was collected from 40 files (n=40) of patients who were on treatment with lithium between 1 January 2017-31 December 2017 at Fort England Hospital. The data was collected retrospectively for both in- and outpatients. Compliance of the monitoring requirements with both South African and international guidelines was analysed. Results and Discussion: In 87.50% (n=37) of the cases, patients had been on lithium therapy before 2017 with most patients (n=13; 37.50%) being maintained on 500 mg of lithium. Non-compliance with the South African and NICE guidelines for renal baseline monitoring was 65.00% (n=26) in both guidelines. Non-compliance for baseline thyroid monitoring was 70.00% (n=28) for both guidelines. There was non-compliance in 45.00% (n=18) of the cases for lithium serum level monitoring for both guidelines. Non-compliance with follow-up renal monitoring was 47.50% (n=19) for both guidelines. Compliance with the NICE guidelines for follow-up metabolic monitoring was 67.50% (n=27). Conclusion: There was non-compliance in most cases leaving room for clinical improvement in the monitoring of lithium. Healthcare professionals should be educated on the recommended monitoring guidelines to promote the rational use of lithium in South Africa. Pharmacists should be more involved in the TDM of lithium to promote its safe and effective use.
- Full Text:
- Date Issued: 2020-04
- Authors: Mapfumo, Charlotte
- Date: 2020-04
- Subjects: Lithium -- Therapeutic use , Psychiatric hospitals -- South Africa -- Grahamstown , Drug utilization , Psychiatric hospital care , Manic-depressive illness , Lithium -- Toxicology , Drug monitoring
- Language: English
- Type: text , Thesis , Masters , M.Pharm
- Identifier: http://hdl.handle.net/10962/150541 , vital:38983
- Description: Bipolar disorder (BD) is a common mental condition that affects about 60 million people globally. Lithium is among the drugs of choice used to treat BD and other affective disorders such as schizoaffective disorder (SD). Lithium is a mood stabiliser with antimanic, antidepressant and anti-suicidal properties. Lithium has complex mechanisms of action and a narrow therapeutic index (NTI). Therapeutic drug monitoring (TDM) is a vital component of lithium therapy due to its NTI. Lithium toxicity can occur at therapeutic levels and is characterised by symptoms such as blurred vision and convulsions. Lithium interacts with a number of drugs resulting in lithium toxicity or diminished effects of lithium. Symptoms of lithium toxicity range from abdominal pain, convulsions and death. Lithium use is associated with serious adverse effects on renal and thyroid function. Other adverse effects include tremor and weight gain. Monitoring of lithium serum levels, renal and thyroid function are therefore recommended for patients on lithium therapy. Monitoring of these parameters assists in the early detection of any problems associated with lithium use. The metabolic monitoring of lithium is vital due to the adverse effect profile of lithium and the current South African Standard Treatment Guidelines Hospital level: Adults, do not have any recommendations for the monitoring of metabolic parameters. The National Institute for Health and Care Excellence (NICE) may be used and adapted for the South African setting. Aim and Objectives: The general aim of the study was to conduct a drug utilisation review (DUR) on lithium through investigating its prescribing and monitoring patterns in both inpatients and outpatients at Fort England Hospital. Methodology: The study was in the form of a retrospective DUR. Data was collected from 40 files (n=40) of patients who were on treatment with lithium between 1 January 2017-31 December 2017 at Fort England Hospital. The data was collected retrospectively for both in- and outpatients. Compliance of the monitoring requirements with both South African and international guidelines was analysed. Results and Discussion: In 87.50% (n=37) of the cases, patients had been on lithium therapy before 2017 with most patients (n=13; 37.50%) being maintained on 500 mg of lithium. Non-compliance with the South African and NICE guidelines for renal baseline monitoring was 65.00% (n=26) in both guidelines. Non-compliance for baseline thyroid monitoring was 70.00% (n=28) for both guidelines. There was non-compliance in 45.00% (n=18) of the cases for lithium serum level monitoring for both guidelines. Non-compliance with follow-up renal monitoring was 47.50% (n=19) for both guidelines. Compliance with the NICE guidelines for follow-up metabolic monitoring was 67.50% (n=27). Conclusion: There was non-compliance in most cases leaving room for clinical improvement in the monitoring of lithium. Healthcare professionals should be educated on the recommended monitoring guidelines to promote the rational use of lithium in South Africa. Pharmacists should be more involved in the TDM of lithium to promote its safe and effective use.
- Full Text:
- Date Issued: 2020-04
An investigation into chemical and biological assays of new compounds from aloes
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
Workplace health promotion at Rhodes University: harmful use of alcohol
- Authors: Marara, Praise
- Date: 2019
- Subjects: Chronic diseases -- South Africa , Health education -- South Africa , Drinking of alcoholic beverages -- Health aspects -- South Africa , Employees -- Alcohol use -- South Africa , Employee health promotion -- South Africa , Rhodes University -- Employees -- Health and hygiene
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/67444 , vital:29088
- Description: Background: Non-communicable diseases (NCDs) are responsible for 38 million deaths annually, which translates to 68% of global deaths every year. Incidence and prevalence of NCDs are increasing rapidly and the poor bear a disproportionate burden. The increase in NCDs has been primarily due to a proliferation of modifiable risk factors, such as unhealthy diet, physical inactivity, tobacco use, and excessive alcohol consumption. Substance abuse, mainly of alcohol, is a common cause of health problems in almost all countries across the globe. Alcohol abuse is a major contributor to the global burden of diseases and accounts for 3.3 million deaths, approximately 5.9% of all global deaths, annually. Alcohol misuse is the fifth leading risk factor for premature death and disability and is the top risk factor among people between 15 and 49 years of age. The rise of harmful use of alcohol in South Africa contributes to the disease burden faced by the country, with alcohol-related disorders making up 44.6% of all alcohol-attributable disabilities. Strategies to reduce harmful use of alcohol include national policies and educational interventions including health promotion. Health promotion is a common practice in the prevention of NCDs, but workplace health promotion has not yet been well established in many workplaces. Identification of past workplace initiatives and exploring their facilitating and limiting factors is thus important to consider when planning future initiatives. Raising awareness on harmful use of alcohol through workplace health promotion projects can help to prevent and reduce alcohol-related problems. For these health promotion activities to succeed, they need to be developed with consideration of factors such as the environment, culture, and socio-economic standing of the intended target population. Method: This study, conducted at Rhodes University, followed a mixed methods research approach and consisted of two phases. The first phase of the current study was a needs assessment and involved working with the key stakeholders. Using the Community Based Participatory Research approach and the Centres for Disease Control and prevention workplace health model to guide the research, five semi-structured interviews were conducted with key stakeholders to identify factors affecting workplace health promotion, and their opinions on how to improve these initiatives were sought. The participants were asked to identify areas on which the intended intervention should focus, as well as to identify their preferred means of communicating health messages. During this phase, a group of peer educators who volunteered their involvement in the health promotion project focusing on harmful use of alcohol was also identified. The second phase of this project aimed to address concerns raised in the first phase through a health promotion initiative for support staff that focuses on the prevention of NCDs diseases through reducing alcohol related harm. During the educational health promotion phase of the study, three health information leaflets based on harmful use of alcohol were designed. These leaflets went through a series of evaluations by the researchers’ peers, support staff during a pilot study, peer educators and other health professionals to assess content validity, context specificity, and cultural appropriateness for the target group. The health information leaflets were then used as written materials in the educational intervention of the project and were also used to design a poster. Through participatory involvement, a facilitator’s manual on harmful use of alcohol was developed, which was used during the workshops in the implementation phase of the research. The facilitator’s manual was modified based on provided feedback on improving the content of the facilitator’s manual. The readability of the manual was also performed to make it suitable for the end users. The peer educators were also trained through workshops to enable them to promote and raise awareness on harmful use of alcohol to others in the workplace. Workshops were participatory in nature and were also equipped with the completed health information leaflets to distribute to their peers and to use as reference sources of information when needed. Results: Participants in the semi-structured interviews reported that some health promotion initiatives have previously been attempted and advertised to support staff, but there was poor participant participation. Peer educators reported that these initiatives were not communicated to them and venues and work commitments sometimes were barriers to participation in these projects. The peer educators suggested incentivising initiatives for better participation. Another key suggestion was to inform and to include their managers and supervisors in these initiatives so they are permitted to take time off work. Health education material like posters or leaflets were also proposed as modes of delivering health information. During the design of the material to be used for this project’s intended intervention, the health information leaflets were deemed readable, suitable, actionable, context-specific, and culturally appropriate. Workshops conducted during Phase 2 of the study proved to be valuable in training peer educators. Peer educators also deemed the workshops useful, and reported their readiness to be agents of change in the workplace. Conclusions: Based on the input of key stakeholders and peer educators, there is currently no health promotion policy at Rhodes University, especially with respect to NCDs health promotion policies and protocols for NCDs. Health promotion initiatives, especially for support staff, that address NCDs have previously been attempted at the university but were not successful. Factors affecting workplace health promotion were identified. Knowledge of these factors was useful when implementing the health promotion project on harmful use of alcohol. The health leaflets were deemed suitable for use by the target population. Peer educators who went through the workshops and were provided with the facilitators’ manuals concluded that the sessions were useful in their continued participation in the health promotion project. Continued involvement of the Wellness Office and peer educators can assist in ensuring the sustainability of this workplace health initiative.
- Full Text:
- Date Issued: 2019
- Authors: Marara, Praise
- Date: 2019
- Subjects: Chronic diseases -- South Africa , Health education -- South Africa , Drinking of alcoholic beverages -- Health aspects -- South Africa , Employees -- Alcohol use -- South Africa , Employee health promotion -- South Africa , Rhodes University -- Employees -- Health and hygiene
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/67444 , vital:29088
- Description: Background: Non-communicable diseases (NCDs) are responsible for 38 million deaths annually, which translates to 68% of global deaths every year. Incidence and prevalence of NCDs are increasing rapidly and the poor bear a disproportionate burden. The increase in NCDs has been primarily due to a proliferation of modifiable risk factors, such as unhealthy diet, physical inactivity, tobacco use, and excessive alcohol consumption. Substance abuse, mainly of alcohol, is a common cause of health problems in almost all countries across the globe. Alcohol abuse is a major contributor to the global burden of diseases and accounts for 3.3 million deaths, approximately 5.9% of all global deaths, annually. Alcohol misuse is the fifth leading risk factor for premature death and disability and is the top risk factor among people between 15 and 49 years of age. The rise of harmful use of alcohol in South Africa contributes to the disease burden faced by the country, with alcohol-related disorders making up 44.6% of all alcohol-attributable disabilities. Strategies to reduce harmful use of alcohol include national policies and educational interventions including health promotion. Health promotion is a common practice in the prevention of NCDs, but workplace health promotion has not yet been well established in many workplaces. Identification of past workplace initiatives and exploring their facilitating and limiting factors is thus important to consider when planning future initiatives. Raising awareness on harmful use of alcohol through workplace health promotion projects can help to prevent and reduce alcohol-related problems. For these health promotion activities to succeed, they need to be developed with consideration of factors such as the environment, culture, and socio-economic standing of the intended target population. Method: This study, conducted at Rhodes University, followed a mixed methods research approach and consisted of two phases. The first phase of the current study was a needs assessment and involved working with the key stakeholders. Using the Community Based Participatory Research approach and the Centres for Disease Control and prevention workplace health model to guide the research, five semi-structured interviews were conducted with key stakeholders to identify factors affecting workplace health promotion, and their opinions on how to improve these initiatives were sought. The participants were asked to identify areas on which the intended intervention should focus, as well as to identify their preferred means of communicating health messages. During this phase, a group of peer educators who volunteered their involvement in the health promotion project focusing on harmful use of alcohol was also identified. The second phase of this project aimed to address concerns raised in the first phase through a health promotion initiative for support staff that focuses on the prevention of NCDs diseases through reducing alcohol related harm. During the educational health promotion phase of the study, three health information leaflets based on harmful use of alcohol were designed. These leaflets went through a series of evaluations by the researchers’ peers, support staff during a pilot study, peer educators and other health professionals to assess content validity, context specificity, and cultural appropriateness for the target group. The health information leaflets were then used as written materials in the educational intervention of the project and were also used to design a poster. Through participatory involvement, a facilitator’s manual on harmful use of alcohol was developed, which was used during the workshops in the implementation phase of the research. The facilitator’s manual was modified based on provided feedback on improving the content of the facilitator’s manual. The readability of the manual was also performed to make it suitable for the end users. The peer educators were also trained through workshops to enable them to promote and raise awareness on harmful use of alcohol to others in the workplace. Workshops were participatory in nature and were also equipped with the completed health information leaflets to distribute to their peers and to use as reference sources of information when needed. Results: Participants in the semi-structured interviews reported that some health promotion initiatives have previously been attempted and advertised to support staff, but there was poor participant participation. Peer educators reported that these initiatives were not communicated to them and venues and work commitments sometimes were barriers to participation in these projects. The peer educators suggested incentivising initiatives for better participation. Another key suggestion was to inform and to include their managers and supervisors in these initiatives so they are permitted to take time off work. Health education material like posters or leaflets were also proposed as modes of delivering health information. During the design of the material to be used for this project’s intended intervention, the health information leaflets were deemed readable, suitable, actionable, context-specific, and culturally appropriate. Workshops conducted during Phase 2 of the study proved to be valuable in training peer educators. Peer educators also deemed the workshops useful, and reported their readiness to be agents of change in the workplace. Conclusions: Based on the input of key stakeholders and peer educators, there is currently no health promotion policy at Rhodes University, especially with respect to NCDs health promotion policies and protocols for NCDs. Health promotion initiatives, especially for support staff, that address NCDs have previously been attempted at the university but were not successful. Factors affecting workplace health promotion were identified. Knowledge of these factors was useful when implementing the health promotion project on harmful use of alcohol. The health leaflets were deemed suitable for use by the target population. Peer educators who went through the workshops and were provided with the facilitators’ manuals concluded that the sessions were useful in their continued participation in the health promotion project. Continued involvement of the Wellness Office and peer educators can assist in ensuring the sustainability of this workplace health initiative.
- Full Text:
- Date Issued: 2019
Development and validation of a health literacy measure for limited literacy public sector patients in South Africa
- Authors: Marimwe, Chipiwa
- Date: 2018
- Subjects: Health literacy -- South Africa , Patient education -- South Africa , Communication in medicine -- South Africa , Health literacy -- Social aspects -- South Africa , Poor -- Medical care -- South Africa , Analysis of variance , Multidimensional Screener of Functional Health Literacy (MSFHL)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/62661 , vital:28227
- Description: The growing complexity of healthcare demands greater patient involvement and skills to navigate this complex system. It has therefore become increasingly important to identify individuals with inadequate health literacy, by using efficient, short and reliable measures for doing so. Most research on the development and validation of health literacy tests has been conducted in high-income countries, with very little reported from low-and middle-income countries (LMICs). Existing health literacy measures have come under scrutiny for their lack of cultural sensitivity, bias towards certain population groups and failure to acknowledge health literacy as a multidimensional concept. These measures usually have limited application in LMICs due to the significantly different structuring of healthcare systems, they overlook the extreme discrepancies in educational levels, and rely too heavily on the ability to read health information. No health literacy data for South Africa are available, and only a few health literacy-based research papers have been published in this country. The aim of the study was to develop and validate a health literacy measure that is contextually and culturally appropriate to measure health literacy in limited literacy public sector patients in South Africa. An Item Bank of 30 questions was developed with the input of a diverse expert consultant panel, and included skills-based and self-reported questions which ensured cultural, contextual and educational level appropriateness. The Information and Support for Health Actions Questionnaire (ISHA-Q) is a health literacy measure developed to assess health literacy for LMICs which includes 14 core scales. These were useful in ensuring coverage of a range of health literacy constructs within the Item Bank. The 30 questions were then allocated to one of three health literacy domains: Procedural knowledge, Factual knowledge and Access to healthcare, health services and social support. Ethical approval for the study was obtained. The questions were translated into isiXhosa and underwent pilot testing. Following pilot testing, 120 isiXhosa first-language speakers, at least 18 years old, who attended public sector facilities and had a maximum 12 years of education were recruited from a primary healthcare clinic in Grahamstown. An interpreter was trained and he participated in all interviews. A questionnaire was used to collect data on the 30-question Item Bank. The Multidimensional Screener of Functional Health Literacy (MSFHL) was used as the primary comparator.The second phase of the study involved the refinement of the 30 questions in the Item Bank, which involved a multi-stage process. Data were analysed statistically using t-test, correlations, chi-square and ANOVA tests at a 5% level of significance, in order to identify problematic questions. Item Response Theory was used to ascertain difficulty and discriminatory ability of the questions. Each question was further subjected to in-depth interrogation by a panel of healthcare professionals to ensure that questions were supported by the conceptual framework and the definitions of health literacy adopted for this study. The number of questions was reduced from 30 to 12, and formed the new Health Literacy Test - Limited Literacy (HELT-LL). To validate the HELT-LL, 210 patients with the same inclusion criteria as previously noted, were recruited from four primary healthcare clinics in the Eastern Cape Province. Individual interviews were conducted with the assistance of the interpreter to collect sociodemographic data as well as data from the HELT-LL, the primary comparator (MSFHL), and a secondary comparator which was a South African modified version of the Newest Vital Sign (NVS-SA). The HELT-LL was re-administered to 40 patients in a follow-up interview two weeks later. The HELT-LL categorised only 17.6% of the patients as having adequate health literacy, just over a third with inadequate health literacy, and the majority with marginal health literacy. Questions in the cognitively demanding Procedural knowledge domain were the most poorly answered, with a mean score of 48.6±24.9%. Patients had great difficulty performing the basic numeric tasks in this domain. The overall mean score for the HELT-LL was 52.8±18.4%, compared with the more cognitively demanding NVS-SA with a mean of 28.6±21.1%, and clearly illustrated the impact of the strategy to include in the HELT-LL a variety of questions with differing cognitive load. The MSFHL, which is based on demographic characteristics and perceived difficulties with reading and writing, had an overall mean score of 44.4±26.2%. Demographic characteristics including age, education and English literacy, were found to be good predictors of limited health literacy, with significant correlations being found between these variables and the mean HELT-LL score. An acceptable value for Cronbach’s alpha, excellent test-retest reliability and excellent concurrent validity show that the HELT-LL is a valid and reliable measure of health literacy in our target population. As there is a paucity of health literacy research emanating from developing countries, this study presents a significant contribution to literature. It is the first study to report the development and validation of a health literacy measure to address the dearth of available health literacy measures applicable for South Africa. If implemented for use in clinical settings and for research purposes, it could provide valuable South African health literacy data which could inform the development of interventions focusing on improving health literacy and health outcomes.
- Full Text:
- Date Issued: 2018
- Authors: Marimwe, Chipiwa
- Date: 2018
- Subjects: Health literacy -- South Africa , Patient education -- South Africa , Communication in medicine -- South Africa , Health literacy -- Social aspects -- South Africa , Poor -- Medical care -- South Africa , Analysis of variance , Multidimensional Screener of Functional Health Literacy (MSFHL)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/62661 , vital:28227
- Description: The growing complexity of healthcare demands greater patient involvement and skills to navigate this complex system. It has therefore become increasingly important to identify individuals with inadequate health literacy, by using efficient, short and reliable measures for doing so. Most research on the development and validation of health literacy tests has been conducted in high-income countries, with very little reported from low-and middle-income countries (LMICs). Existing health literacy measures have come under scrutiny for their lack of cultural sensitivity, bias towards certain population groups and failure to acknowledge health literacy as a multidimensional concept. These measures usually have limited application in LMICs due to the significantly different structuring of healthcare systems, they overlook the extreme discrepancies in educational levels, and rely too heavily on the ability to read health information. No health literacy data for South Africa are available, and only a few health literacy-based research papers have been published in this country. The aim of the study was to develop and validate a health literacy measure that is contextually and culturally appropriate to measure health literacy in limited literacy public sector patients in South Africa. An Item Bank of 30 questions was developed with the input of a diverse expert consultant panel, and included skills-based and self-reported questions which ensured cultural, contextual and educational level appropriateness. The Information and Support for Health Actions Questionnaire (ISHA-Q) is a health literacy measure developed to assess health literacy for LMICs which includes 14 core scales. These were useful in ensuring coverage of a range of health literacy constructs within the Item Bank. The 30 questions were then allocated to one of three health literacy domains: Procedural knowledge, Factual knowledge and Access to healthcare, health services and social support. Ethical approval for the study was obtained. The questions were translated into isiXhosa and underwent pilot testing. Following pilot testing, 120 isiXhosa first-language speakers, at least 18 years old, who attended public sector facilities and had a maximum 12 years of education were recruited from a primary healthcare clinic in Grahamstown. An interpreter was trained and he participated in all interviews. A questionnaire was used to collect data on the 30-question Item Bank. The Multidimensional Screener of Functional Health Literacy (MSFHL) was used as the primary comparator.The second phase of the study involved the refinement of the 30 questions in the Item Bank, which involved a multi-stage process. Data were analysed statistically using t-test, correlations, chi-square and ANOVA tests at a 5% level of significance, in order to identify problematic questions. Item Response Theory was used to ascertain difficulty and discriminatory ability of the questions. Each question was further subjected to in-depth interrogation by a panel of healthcare professionals to ensure that questions were supported by the conceptual framework and the definitions of health literacy adopted for this study. The number of questions was reduced from 30 to 12, and formed the new Health Literacy Test - Limited Literacy (HELT-LL). To validate the HELT-LL, 210 patients with the same inclusion criteria as previously noted, were recruited from four primary healthcare clinics in the Eastern Cape Province. Individual interviews were conducted with the assistance of the interpreter to collect sociodemographic data as well as data from the HELT-LL, the primary comparator (MSFHL), and a secondary comparator which was a South African modified version of the Newest Vital Sign (NVS-SA). The HELT-LL was re-administered to 40 patients in a follow-up interview two weeks later. The HELT-LL categorised only 17.6% of the patients as having adequate health literacy, just over a third with inadequate health literacy, and the majority with marginal health literacy. Questions in the cognitively demanding Procedural knowledge domain were the most poorly answered, with a mean score of 48.6±24.9%. Patients had great difficulty performing the basic numeric tasks in this domain. The overall mean score for the HELT-LL was 52.8±18.4%, compared with the more cognitively demanding NVS-SA with a mean of 28.6±21.1%, and clearly illustrated the impact of the strategy to include in the HELT-LL a variety of questions with differing cognitive load. The MSFHL, which is based on demographic characteristics and perceived difficulties with reading and writing, had an overall mean score of 44.4±26.2%. Demographic characteristics including age, education and English literacy, were found to be good predictors of limited health literacy, with significant correlations being found between these variables and the mean HELT-LL score. An acceptable value for Cronbach’s alpha, excellent test-retest reliability and excellent concurrent validity show that the HELT-LL is a valid and reliable measure of health literacy in our target population. As there is a paucity of health literacy research emanating from developing countries, this study presents a significant contribution to literature. It is the first study to report the development and validation of a health literacy measure to address the dearth of available health literacy measures applicable for South Africa. If implemented for use in clinical settings and for research purposes, it could provide valuable South African health literacy data which could inform the development of interventions focusing on improving health literacy and health outcomes.
- Full Text:
- Date Issued: 2018
Medicine use in swallowing-impaired patients: Pharmacists’ knowledge, practice and information needs
- Authors: Masilamoney, Mehrusha
- Date: 2018
- Subjects: Deglutition disorders , Drugs -- Administration , Oral medication -- Administration , Pharmacists -- Practice , South African Pharmacy Council
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/61940 , vital:28086
- Description: Dysphagia, or swallowing impairment, is a growing problem that affects 13.5% of the general population. The ability to swallow is essential for patients taking oral medicines, so this presents a challenge for swallowing-impaired (SI) patients as tablets and capsules will usually require modification prior to ingestion. Pharmacists should play a central role in advising SI patients about their medicine use, as well as problems that may impact on safety, adherence and therapeutic outcome. However, little is known about pharmacists’ level of knowledge, their practice and their information needs when dealing with SI patients and their use of medicines. The aim of this study was to investigate pharmacist knowledge, practice and information needs relating to the support of SI patients and their medicine-related needs. The study design included both quantitative and qualitative methods. A quantitative questionnaire was developed to collect data on the knowledge, practice and information needs of pharmacists and was piloted in 10 pharmacists, which resulted in minor modifications. The questionnaire was converted to a web-based survey and emailed to all pharmacists registered with the South African Pharmacy Council. Two knowledge scores were generated by summating correct responses: knowledge of dysphagia (KOD) and knowledge of medicine use (KOMU) in SI patients. Correlation analysis was used to investigate the strength of the relationship between specific variables with KOD and KOMU using the Pearson correlation coefficient. Qualitative semi-structured interviews were conducted with pharmacists from community, hospital and primary healthcare clinics in both a small town and a major metropole. The aim was to gain deeper understanding of issues arising from the survey, and to explore preferences for topic-specific information materials. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. A total of 439 pharmacists responded to the survey, with 67% being females.The mean KOD score out of a maximum score of 10 was 6.1 ± 1.8. KOD was inadequate (<5) in just over one-third (37.8%) of pharmacists. The mean KOMU score achieved (maximum score 17) was 9.4 ± 2.0, with inadequate knowledge (<10) being established in just over two-thirds of pharmacists (70.8%). Age, length of registration as a pharmacist, and years of practice in a setting with direct patient interaction were significantly but weakly correlated with KOMU, whereas KOD showed no significant association with these variables. Qualification significantly influenced both KOD and KOMU; the highest group with adequate knowledge had either a Masters or a PharmD degree. Fewer than half the pharmacists (44%) never ask patients about their swallowing ability, and most (86%) reported no knowledge of locally available viscosity enhancers. Almost all pharmacists were interested in receiving information materials on assisting SI patients with their medicine use. Three major themes emerged from the semi-structured interviews. Pharmacists recognised their knowledge deficit and felt that lack of both undergraduate training and formal training during practice, as well as limited exposure to SI patients, were contributing factors. Barriers to their practice with SI patients included lack of time, lack of institutional support and lack of easily accessible references on the pharmacists’ role in supporting medicine use in SI patients. Lastly, most pharmacists were not prepared to take ownership of medicine-related problems in SI patients and had conflicting opinions of the pharmacists’ role, usually shifting the responsibility of medicine use in SI patients to nurses. This is the first study to investigate pharmacist knowledge of medicine use in SI patients. The findings indicate that pharmacists do not have the requisite knowledge when dealing with SI patients and their medicine-taking issues despite being the most highly trained healthcare professionals in this field. Lack of undergraduate training, in-house training and limited exposure to SI patients were reported to contribute to poor knowledge. Current practice revealed that there appears to be poor communication among different healthcare professionals, pharmacists were reluctant to work with and/or train nurses on appropriate medicine use in SI patients, and there appeared to be ambiguity surrounding the role of a pharmacist. This research identified that pharmacists regard this topic to be highly relevant to their everyday practice and are keen to receive more information and training relating to this area of study. Information materials were designed and will be made accessible to all pharmacists registered in South Africa.
- Full Text:
- Date Issued: 2018
Medicine use in swallowing-impaired patients: Pharmacists’ knowledge, practice and information needs
- Authors: Masilamoney, Mehrusha
- Date: 2018
- Subjects: Deglutition disorders , Drugs -- Administration , Oral medication -- Administration , Pharmacists -- Practice , South African Pharmacy Council
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/61940 , vital:28086
- Description: Dysphagia, or swallowing impairment, is a growing problem that affects 13.5% of the general population. The ability to swallow is essential for patients taking oral medicines, so this presents a challenge for swallowing-impaired (SI) patients as tablets and capsules will usually require modification prior to ingestion. Pharmacists should play a central role in advising SI patients about their medicine use, as well as problems that may impact on safety, adherence and therapeutic outcome. However, little is known about pharmacists’ level of knowledge, their practice and their information needs when dealing with SI patients and their use of medicines. The aim of this study was to investigate pharmacist knowledge, practice and information needs relating to the support of SI patients and their medicine-related needs. The study design included both quantitative and qualitative methods. A quantitative questionnaire was developed to collect data on the knowledge, practice and information needs of pharmacists and was piloted in 10 pharmacists, which resulted in minor modifications. The questionnaire was converted to a web-based survey and emailed to all pharmacists registered with the South African Pharmacy Council. Two knowledge scores were generated by summating correct responses: knowledge of dysphagia (KOD) and knowledge of medicine use (KOMU) in SI patients. Correlation analysis was used to investigate the strength of the relationship between specific variables with KOD and KOMU using the Pearson correlation coefficient. Qualitative semi-structured interviews were conducted with pharmacists from community, hospital and primary healthcare clinics in both a small town and a major metropole. The aim was to gain deeper understanding of issues arising from the survey, and to explore preferences for topic-specific information materials. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. A total of 439 pharmacists responded to the survey, with 67% being females.The mean KOD score out of a maximum score of 10 was 6.1 ± 1.8. KOD was inadequate (<5) in just over one-third (37.8%) of pharmacists. The mean KOMU score achieved (maximum score 17) was 9.4 ± 2.0, with inadequate knowledge (<10) being established in just over two-thirds of pharmacists (70.8%). Age, length of registration as a pharmacist, and years of practice in a setting with direct patient interaction were significantly but weakly correlated with KOMU, whereas KOD showed no significant association with these variables. Qualification significantly influenced both KOD and KOMU; the highest group with adequate knowledge had either a Masters or a PharmD degree. Fewer than half the pharmacists (44%) never ask patients about their swallowing ability, and most (86%) reported no knowledge of locally available viscosity enhancers. Almost all pharmacists were interested in receiving information materials on assisting SI patients with their medicine use. Three major themes emerged from the semi-structured interviews. Pharmacists recognised their knowledge deficit and felt that lack of both undergraduate training and formal training during practice, as well as limited exposure to SI patients, were contributing factors. Barriers to their practice with SI patients included lack of time, lack of institutional support and lack of easily accessible references on the pharmacists’ role in supporting medicine use in SI patients. Lastly, most pharmacists were not prepared to take ownership of medicine-related problems in SI patients and had conflicting opinions of the pharmacists’ role, usually shifting the responsibility of medicine use in SI patients to nurses. This is the first study to investigate pharmacist knowledge of medicine use in SI patients. The findings indicate that pharmacists do not have the requisite knowledge when dealing with SI patients and their medicine-taking issues despite being the most highly trained healthcare professionals in this field. Lack of undergraduate training, in-house training and limited exposure to SI patients were reported to contribute to poor knowledge. Current practice revealed that there appears to be poor communication among different healthcare professionals, pharmacists were reluctant to work with and/or train nurses on appropriate medicine use in SI patients, and there appeared to be ambiguity surrounding the role of a pharmacist. This research identified that pharmacists regard this topic to be highly relevant to their everyday practice and are keen to receive more information and training relating to this area of study. Information materials were designed and will be made accessible to all pharmacists registered in South Africa.
- Full Text:
- Date Issued: 2018
A self-emulsifying delivery system loaded with efavirenz: The case for flax-seed oil
- Authors: Mazonde, Priveledge
- Date: 2021-10-29
- Subjects: Drug delivery systems , Linseed oil , Antiretroviral agents , HIV (Viruses) , Drug carriers (Pharmacy) , Solubility , High performance liquid chromatography , Efavirenz
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192944 , vital:45283
- Description: The feasibility of incorporating efavirenz (EFV), an antiretroviral agent against HIV into a lipid-based self-emulsifying drug delivery system (SEDDS) containing vegetable oils was investigated. EFV has poor aqueous solubility and is classified under the Biopharmaceutical Classification System (BCS) as a class II compound with highly permeability, its aqueous solubility is less than 10 mg/ml and is defined as a practically insoluble compound with a consequent poor bioavailability of approximately 40%, and erratic dissolution behaviour. SEDDS formulations have been shown to improve the aqueous solubility and consequently the bioavailability of BCS II compounds such as EFV. EFV is a first line antiviral agent used in combination with other agents in antiretroviral therapy (ART). Among the number of NNRTIs approved for use in HIV treatment, EFV is one of the most commonly prescribed drug. Statistical methods and Design of Experiments (DoE) using Response Surface Methodology (RSM), specifically a Central Composite Design (CCD), were used to facilitate the development of a reversed-phase high performance liquid chromatographic (HPLC) method for the quantitation of EFV during formulation product and process development studies. A rapid, accurate, precise and sensitive HPLC method with ultraviolet (UV) detection was developed, optimised and validated for the in-vitro analysis of EFV in a total run time under 10 minutes for the elution of both EFV and loratidine which was used as the internal standard (IS). The method was then successfully applied to the determination of EFV in commercially available tablets. Excipient screening was undertaken using solubility studies and revealed that EFV had highest solubility in flaxseed oil in comparison to soybean, macadamia, grapeseed, sunflower and olive oils. The non-ionic Tween® 80 and Span® 20 were selected as surfactant and co-surfactant, respectively with ethanol co-solvent as they exhibited improved miscibility with co-solvent. Pre-formulation studies were undertaken to investigate the compatibility of the API with excipients and to identify a nano-emulsion region and other emulsion types using pseudoternary phase diagrams. The phase behaviour of crude cold pressed flaxseed oil with the selected non-ionic surfactants revealed an area within pseudo-ternary phase diagrams for different surfactant-mixtures formed gels/semisolid structures which can be exploited for other drug delivery strategies that require such properties. Fourier transform infrared spectroscopy (FT-IR), powder x-ray diffraction (XRD) and Raman spectroscopy were used to identify and assess the compatibility of EFV with chosen excipients. 2 A reduction in the peak intensity was observed for EFV when combined with each hydrophobic/lipid excipient evaluated revealing that there was a marked reduction in the crystallinity of the EFV. A decrease in crystallinity in comparison with the bulk API may indicate that EFV were amorphous or sequestered in a molecular dispersion and exhibited an increased solubility for the molecule. Flaxseed oil was used as the oil phase in studies for the optimization of surfactant mixtures undertaken using DoE, specifically a D-optimal mixtures design with the flaxseed oil content set at 10% m/m was performed. Solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, drug loading capacity, Zeta Potential, droplet sizes and polydispersity index (PDI). Kinetically stable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and assessed. Droplet sizes ranged between 156 and 225 nm, Zeta Potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487. SEDDS formulations of EFV in nano-sized carriers were developed and optimised, in vitro drug release varied with varying amounts of ethanol in the formulation producing formulations that exhibited differently modulated drug in-vitro release profiles that may be further manipulated for better performance and therapeutic outcomes in terms of solubility and possibly bioavailability of EFV when delivered using SEDDS rather than using tablets which in turn may lead to better therapeutic outcomes for patients with HIV. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Mazonde, Priveledge
- Date: 2021-10-29
- Subjects: Drug delivery systems , Linseed oil , Antiretroviral agents , HIV (Viruses) , Drug carriers (Pharmacy) , Solubility , High performance liquid chromatography , Efavirenz
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192944 , vital:45283
- Description: The feasibility of incorporating efavirenz (EFV), an antiretroviral agent against HIV into a lipid-based self-emulsifying drug delivery system (SEDDS) containing vegetable oils was investigated. EFV has poor aqueous solubility and is classified under the Biopharmaceutical Classification System (BCS) as a class II compound with highly permeability, its aqueous solubility is less than 10 mg/ml and is defined as a practically insoluble compound with a consequent poor bioavailability of approximately 40%, and erratic dissolution behaviour. SEDDS formulations have been shown to improve the aqueous solubility and consequently the bioavailability of BCS II compounds such as EFV. EFV is a first line antiviral agent used in combination with other agents in antiretroviral therapy (ART). Among the number of NNRTIs approved for use in HIV treatment, EFV is one of the most commonly prescribed drug. Statistical methods and Design of Experiments (DoE) using Response Surface Methodology (RSM), specifically a Central Composite Design (CCD), were used to facilitate the development of a reversed-phase high performance liquid chromatographic (HPLC) method for the quantitation of EFV during formulation product and process development studies. A rapid, accurate, precise and sensitive HPLC method with ultraviolet (UV) detection was developed, optimised and validated for the in-vitro analysis of EFV in a total run time under 10 minutes for the elution of both EFV and loratidine which was used as the internal standard (IS). The method was then successfully applied to the determination of EFV in commercially available tablets. Excipient screening was undertaken using solubility studies and revealed that EFV had highest solubility in flaxseed oil in comparison to soybean, macadamia, grapeseed, sunflower and olive oils. The non-ionic Tween® 80 and Span® 20 were selected as surfactant and co-surfactant, respectively with ethanol co-solvent as they exhibited improved miscibility with co-solvent. Pre-formulation studies were undertaken to investigate the compatibility of the API with excipients and to identify a nano-emulsion region and other emulsion types using pseudoternary phase diagrams. The phase behaviour of crude cold pressed flaxseed oil with the selected non-ionic surfactants revealed an area within pseudo-ternary phase diagrams for different surfactant-mixtures formed gels/semisolid structures which can be exploited for other drug delivery strategies that require such properties. Fourier transform infrared spectroscopy (FT-IR), powder x-ray diffraction (XRD) and Raman spectroscopy were used to identify and assess the compatibility of EFV with chosen excipients. 2 A reduction in the peak intensity was observed for EFV when combined with each hydrophobic/lipid excipient evaluated revealing that there was a marked reduction in the crystallinity of the EFV. A decrease in crystallinity in comparison with the bulk API may indicate that EFV were amorphous or sequestered in a molecular dispersion and exhibited an increased solubility for the molecule. Flaxseed oil was used as the oil phase in studies for the optimization of surfactant mixtures undertaken using DoE, specifically a D-optimal mixtures design with the flaxseed oil content set at 10% m/m was performed. Solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, drug loading capacity, Zeta Potential, droplet sizes and polydispersity index (PDI). Kinetically stable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and assessed. Droplet sizes ranged between 156 and 225 nm, Zeta Potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487. SEDDS formulations of EFV in nano-sized carriers were developed and optimised, in vitro drug release varied with varying amounts of ethanol in the formulation producing formulations that exhibited differently modulated drug in-vitro release profiles that may be further manipulated for better performance and therapeutic outcomes in terms of solubility and possibly bioavailability of EFV when delivered using SEDDS rather than using tablets which in turn may lead to better therapeutic outcomes for patients with HIV. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-10-29
An investigation into the anxiolytic properties of melatonin in humans
- McCallaghan, Johannes Jacobus
- Authors: McCallaghan, Johannes Jacobus
- Date: 1999
- Subjects: Melatonin , Pineal gland -- Secretions
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3772 , http://hdl.handle.net/10962/d1003250 , Melatonin , Pineal gland -- Secretions
- Description: The purpose of this project was to investigate the role of melatonin in the pathophysiology of anxiety in humans. The literature study confirmed the intimate relationship between serotonin and melatonin. Melatonin is not only able to act as an agonist (in physiological concentrations) and an antagonist (at higher concentrations) on serotonin receptors but via control of brain pyridoxal kinase activity might have an effect on GABA, serotonin, dopamine and norepinephrine synthesis. A clinical trial to investigate melatonin's effect on anxiety in humans was conducted as a pilot study. Thirty patients complaining of anxiety participated in a liN of 1" double blind placebo controlled trial. During the experiment each subject was thus exposed to melatonin and a placebo for a week at a time on two occasions. During the first phase of the experiment, (Pair '1) patients showed a statistically significant reduction in their anxiety levels during the first period (P1P1), which was not the case during the second period (P1P2). The improvement however continued during the second phase of the experiment (Pair 2) so that there was also a statistically significant improvement during P 2 P 2 (Period 2 / Pair 2) when placebo was administered. It could not conclusively be shown that melatonin was responsible for the improvement in the patients' anxiety. The explanation for these results suggests thelt the improvement was due to a: 1) placebo effect throughout, 2) psychotherapeutic effect due to contact with a clinician, 3) melatonin induced phase shift in the patient's endogenous melatonin response curve, 4) combination of all 3 options. This pilot study lays the groundwork for a much more exhaustive study in which the melatonin of the patients is determined before melatonin is administered, the role of the clinician is clarified and the most appropriate time for melatonin administration is sought .
- Full Text:
- Date Issued: 1999
- Authors: McCallaghan, Johannes Jacobus
- Date: 1999
- Subjects: Melatonin , Pineal gland -- Secretions
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3772 , http://hdl.handle.net/10962/d1003250 , Melatonin , Pineal gland -- Secretions
- Description: The purpose of this project was to investigate the role of melatonin in the pathophysiology of anxiety in humans. The literature study confirmed the intimate relationship between serotonin and melatonin. Melatonin is not only able to act as an agonist (in physiological concentrations) and an antagonist (at higher concentrations) on serotonin receptors but via control of brain pyridoxal kinase activity might have an effect on GABA, serotonin, dopamine and norepinephrine synthesis. A clinical trial to investigate melatonin's effect on anxiety in humans was conducted as a pilot study. Thirty patients complaining of anxiety participated in a liN of 1" double blind placebo controlled trial. During the experiment each subject was thus exposed to melatonin and a placebo for a week at a time on two occasions. During the first phase of the experiment, (Pair '1) patients showed a statistically significant reduction in their anxiety levels during the first period (P1P1), which was not the case during the second period (P1P2). The improvement however continued during the second phase of the experiment (Pair 2) so that there was also a statistically significant improvement during P 2 P 2 (Period 2 / Pair 2) when placebo was administered. It could not conclusively be shown that melatonin was responsible for the improvement in the patients' anxiety. The explanation for these results suggests thelt the improvement was due to a: 1) placebo effect throughout, 2) psychotherapeutic effect due to contact with a clinician, 3) melatonin induced phase shift in the patient's endogenous melatonin response curve, 4) combination of all 3 options. This pilot study lays the groundwork for a much more exhaustive study in which the melatonin of the patients is determined before melatonin is administered, the role of the clinician is clarified and the most appropriate time for melatonin administration is sought .
- Full Text:
- Date Issued: 1999
The phytochemistry of several South African aloe species
- Authors: McCarthy, Terence John
- Date: 1967
- Subjects: Botanical chemistry Aloe -- Research -- South Africa Aloe -- Analysis Medicinal plants -- Research -- South Africa Drugs -- Research Chromatographic analysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3836 , http://hdl.handle.net/10962/d1007621
- Description: Introduction: Despite the tremendous advances made with regard to synthetic organic medicinals within the last two decades, heavy reliance is still placed on plant products. This is especially true of the anthracene derivatives used medicinally as purgatives, and which are derived principally from senna, cascara, rhubarb, frangula and aloes. While particular attention has been paid to the chemistry of the former group in recent years, aloes has been largely neglected, possibly due to the fact that the Aloe species are confined largely to areas where extensive research facilities are lacking, such as Africa , India and the West Indies. Thus research in Europe has been confined largely to the lump aloes of commerce, derived from relatively few species. In 1953 a comprehensive report by Hodge (103) appeared on "The Drug Aloes of Commerce, with Special Reference to the Cape Species". Hodge observed that South Africa abounds in species just as abundant as A.ferox, (which is the prime source of Cape aloes), and advised that a systematic chemical survey might show certain of these to be not only higher yielders of bitter aloetic juice but also sources of a superior drug product. Consequently an investigation along these lines is presented here, and it is observed that several species apart from A.ferox not only contain aloin, but also yield a large volume of aloetic juice. Only pharmacologic studies can reveal if the juice of these species is as safe as that of A.ferox, but without doubt they could be used for the extraction of crystalline aloin. Concurrently, the distribution of the Aloe resins, said by some to be purgative themselves, has been studied. The investigation has revealed that the structurally similar compound homonataloin enjoys an equally wide distribution as aloin. However, almost invariably it is confined to small species yielding little aloetic juice, apart from which nothing is known regarding its pharmacologic properties. It is interesting to note that the resin distribution in the homonataloin-containing species is very similar to that of the aloin-containing species, but differs widely from. that of the species containing neither of these principles. Apart from aloin and homonataloin, aloinoside and chrysophanol also occur in Aloe species, and together with the resins, these indicate that when all the South African Aloe species have been investigated, they may well be of chemotaxonomic value. Within the comparatively short space of the last decade some work has been performed on aspects of the metabolism of such anthracene-containing species as Rheum, Rhamnus and Rumex. These investigations have shown that the anthracene derivatives are not merely waste products, but perform definite metabolic functions. The latter portion of this work has been devoted to this relatively neglected aspect of the Aloe species.
- Full Text:
- Date Issued: 1967
- Authors: McCarthy, Terence John
- Date: 1967
- Subjects: Botanical chemistry Aloe -- Research -- South Africa Aloe -- Analysis Medicinal plants -- Research -- South Africa Drugs -- Research Chromatographic analysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3836 , http://hdl.handle.net/10962/d1007621
- Description: Introduction: Despite the tremendous advances made with regard to synthetic organic medicinals within the last two decades, heavy reliance is still placed on plant products. This is especially true of the anthracene derivatives used medicinally as purgatives, and which are derived principally from senna, cascara, rhubarb, frangula and aloes. While particular attention has been paid to the chemistry of the former group in recent years, aloes has been largely neglected, possibly due to the fact that the Aloe species are confined largely to areas where extensive research facilities are lacking, such as Africa , India and the West Indies. Thus research in Europe has been confined largely to the lump aloes of commerce, derived from relatively few species. In 1953 a comprehensive report by Hodge (103) appeared on "The Drug Aloes of Commerce, with Special Reference to the Cape Species". Hodge observed that South Africa abounds in species just as abundant as A.ferox, (which is the prime source of Cape aloes), and advised that a systematic chemical survey might show certain of these to be not only higher yielders of bitter aloetic juice but also sources of a superior drug product. Consequently an investigation along these lines is presented here, and it is observed that several species apart from A.ferox not only contain aloin, but also yield a large volume of aloetic juice. Only pharmacologic studies can reveal if the juice of these species is as safe as that of A.ferox, but without doubt they could be used for the extraction of crystalline aloin. Concurrently, the distribution of the Aloe resins, said by some to be purgative themselves, has been studied. The investigation has revealed that the structurally similar compound homonataloin enjoys an equally wide distribution as aloin. However, almost invariably it is confined to small species yielding little aloetic juice, apart from which nothing is known regarding its pharmacologic properties. It is interesting to note that the resin distribution in the homonataloin-containing species is very similar to that of the aloin-containing species, but differs widely from. that of the species containing neither of these principles. Apart from aloin and homonataloin, aloinoside and chrysophanol also occur in Aloe species, and together with the resins, these indicate that when all the South African Aloe species have been investigated, they may well be of chemotaxonomic value. Within the comparatively short space of the last decade some work has been performed on aspects of the metabolism of such anthracene-containing species as Rheum, Rhamnus and Rumex. These investigations have shown that the anthracene derivatives are not merely waste products, but perform definite metabolic functions. The latter portion of this work has been devoted to this relatively neglected aspect of the Aloe species.
- Full Text:
- Date Issued: 1967
Development and assessment of a smart thermosetting intranasal hydrogel for lamotrigine
- Authors: Melamane, Siyabonga
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62975 , vital:28349
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
- Authors: Melamane, Siyabonga
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62975 , vital:28349
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
A critical evaluation of the human skin blanching assay and comparative bioavailability studies on topical corticosteroid preparations
- Authors: Meyer, Eric
- Date: 1989
- Subjects: Dermatopharmacology Skin, Effect of drugs on Adrenocortical hormones
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3727 , http://hdl.handle.net/10962/d1001464
- Description: Several aspects of the human skin blanching assay were evaluated in an attempt to suggest improvements in the methodology of this assay. Three trials were performed in the unoccluded application mode, using two proprietary creams containing 0,1% betamethasone (as the 17-valerate). Preliminary observations of the influence of ambient temperature and relative humidity on the blanching response did not allow definite conclusions to be drawn. Studies on the number of observers required for reliable results of comparative blanching indicated that at least two trained observers should be employed. Analyses of the results of individual volunteers demonstrated the expected biological variability, and suggest that subjects selected for trials should represent a range of blanching responses. No sex-related differences in blanching responses were found, and both arms exhibited similar sensitivity to corticosteroids. Retrospective analysis of 95 040 observations of blanching responses showed that in the unoccluded application mode blanching is lowest close to the wrist, and in the occluded mode blanching is lowest close to the elbow. Studies on the method of transportation of Betnovate preparations suggest that topical formulations should not be exposed to temperature extremes during transportation. It is proposed that patients should not transport topical formulations in the holds of ships or aircraft, and that exporters and manufacturers should make use of special transportation and storage conditions. In a study of ten topical formulations from three countries it was found that there was no trend of products from one country consistently exhibiting superior blanching to products from the other two countries, or products from one country consistently exhibiting the lowest degree of blanching, although considerable differences in blanching responses were found in some cases. Interpretation of the results of these studies demonstrated the importance of employing a combination of statistical analyses, blanching profiles and AUC values when drawing conclusions regarding comparative bioavailability. A study of the blanching profiles of Betnovate cream included in all 16 trials performed during this work indicated that this preparation behaved in a similar fashion during all trials, thereby giving credence to the results of the trials
- Full Text:
- Date Issued: 1989
- Authors: Meyer, Eric
- Date: 1989
- Subjects: Dermatopharmacology Skin, Effect of drugs on Adrenocortical hormones
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3727 , http://hdl.handle.net/10962/d1001464
- Description: Several aspects of the human skin blanching assay were evaluated in an attempt to suggest improvements in the methodology of this assay. Three trials were performed in the unoccluded application mode, using two proprietary creams containing 0,1% betamethasone (as the 17-valerate). Preliminary observations of the influence of ambient temperature and relative humidity on the blanching response did not allow definite conclusions to be drawn. Studies on the number of observers required for reliable results of comparative blanching indicated that at least two trained observers should be employed. Analyses of the results of individual volunteers demonstrated the expected biological variability, and suggest that subjects selected for trials should represent a range of blanching responses. No sex-related differences in blanching responses were found, and both arms exhibited similar sensitivity to corticosteroids. Retrospective analysis of 95 040 observations of blanching responses showed that in the unoccluded application mode blanching is lowest close to the wrist, and in the occluded mode blanching is lowest close to the elbow. Studies on the method of transportation of Betnovate preparations suggest that topical formulations should not be exposed to temperature extremes during transportation. It is proposed that patients should not transport topical formulations in the holds of ships or aircraft, and that exporters and manufacturers should make use of special transportation and storage conditions. In a study of ten topical formulations from three countries it was found that there was no trend of products from one country consistently exhibiting superior blanching to products from the other two countries, or products from one country consistently exhibiting the lowest degree of blanching, although considerable differences in blanching responses were found in some cases. Interpretation of the results of these studies demonstrated the importance of employing a combination of statistical analyses, blanching profiles and AUC values when drawing conclusions regarding comparative bioavailability. A study of the blanching profiles of Betnovate cream included in all 16 trials performed during this work indicated that this preparation behaved in a similar fashion during all trials, thereby giving credence to the results of the trials
- Full Text:
- Date Issued: 1989
Comparative bioavailability and ranking of topical corticosteroid formulations
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
- Full Text:
- Date Issued: 1985
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
- Full Text:
- Date Issued: 1985
Development and manufacture of sustained release captopril beads
- Authors: Mhaka, Farai Arthur
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54712 , vital:26602
- Description: Hypertension has a high mortality rate in developing countries such as South Africa. Although the prevention and control of hypertension is a health priority, efforts to decrease the global burden of hypertension and improve control over the condition are inadequate. The use of angiotensin converting enzyme (ACE) inhibitors such as captopril (CPT) have been effective for the management of hypertension when used as first line therapy alone or in combination. Commercially available immediate release dosage forms containing 12.5, 25 and 50 mg of CPT are administered two or three times a day to treat hypertension. CPT degrades in aqueous media with the sulfhydryl functional moiety responsible for adverse effects such as hypersensitivity, taste disturbances and/or presenting with a dry hacking cough. CPT has a short elimination half-life of between 1.6 and 1.9 hours, which means that the compound is a suitable candidate for inclusion in sustained release (SR) dosage forms. Manufacturing a SR dosage form of coated beads for twice daily dosing may reduce the incidence and intensity of undesirable adverse effects, improve the stability of CPT and improve patient adherence. A stability indicating reversed-phase high performance liquid chromatographic (RP-HPLC) method was developed and optimised using a central composite design approach. As part of this approach the interactive effects of input factors, viz. pH, methanol (MeOH) content and column temperature on retention time, were investigated to achieve a separation with well-resolved and symmetrical peaks for CPT and salicylic acid. The method was validated using ICH guidelines and was found to be simple, linear, precise, accurate, selective and rapid for the in vitro quantitation of CPT. The method was successfully applied for the analysis of both commercially available and test formulations. Preformulation studies were undertaken to establish the physical and chemical properties of CPT, excipients and dosage forms to ensure the production of stabile and bioavailable products. Powder blends were assessed for flow properties using angle of repose (AOR), and bulk and tapped density, which were subsequently used to calculate Carr’s Index (CI) and the Hausner ratio (HR). The addition of talc resulted in the most powder blends with AOR, CI and HR that were within a range indicative of satisfactory to good flow properties. The use of talc was necessary to ensure that blending prior to wet granulation and extrusion-spheronisation would produce homogenous powders. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were used for the identification and purity of CPT alone and 1:1 binary mixtures with excipients in an effort to establish if CPT was likely to undergo physical and/or chemical modification during production. The DSC thermograms for all CPT-excipient mixtures revealed the presence of a melting endotherm that was wider, occurring at 110.93 °C (Tpeak for pure CPT). The characteristic peaks for specific functional groups were present in the FT-IR spectra for powder mixtures, indicating the absence of incompatibilities. Dialysis studies were used to investigate if the ammonium oleate present in Surelease® E-7-19010 interacted with CPT. The results suggests that an interaction between CPT and Surelease® E-7-19010 during processing of CPT beads was unlikely to occur. Preliminary investigations reveal that Methocel® K100M, Methocel® E4M, Avicel® PH102, Eudragit® RS PO, Surelease® E-7-19010 and talc are compatible with CPT and could be used for the manufacture of SR CPT beads. CPT beads were manufactured using extrusion-spheronisation and coated using a fluidised bed drier fitted with a Wurster insert. The amount of granulating fluid, coating levels, curing time and formulation composition were varied to achieve CPT release with specific criteria to develop a preliminary formulation. The coated beads met all desired quality attributes in respect of micromeritic and flow properties, content uniformity and friability. Response Surface Methodology was used to further optimise the SR CPT formulation. The Plackett-Burman design was used for this process to produce an SR dosage form with desirable quality attributes achieved by altering formulation composition, extrusion-spheronisation variables and coating parameters. ANOVA data revealed significant responses for yield, aspect ratio, sphericity, coating efficiency and cumulative percent CPT released at 2 and 12 hours. Formulations in which the high molecular weight HPMC were used in increased concentrations resulted in the formation of a sticky wet mass and extrudate, resulting in a decrease in yield. The application of a permeable, but insoluble Surelease® coat onto the surface of the beads formed a barrier that complements the activity of the hydrophilic matrix in preventing rapid dissolution and retarding the release of CPT from the beads. The amount of CPT released over 12 hours revealed that increasing the Methocel® K100M content entrapped CPT and retained it more efficiently in the hydrated matrix, resulting in a slow rate of CPT release. In vitro release data were fitted to a number of models in an attempt to elucidate mechanistic aspects of transport processes specific to CPT from the coated bead formulations. The results of fitting data from optimised batches revealed that the goodness of fit based on the adjusted correlation coefficient ranged between 0.953 and 0.976 for the Higuchi model, indicating that diffusion is a predominant factor that controls CPT release from the coated beads. The results of fitting data to the Korsmeyer-Peppas model suggest that the mechanism of CPT release includes transport of the dissolution medium from the vessel reservoir into the core of the bead due to osmotic potential, dissolution of CPT, mass transfer of the dissolved CPT within the core, partitioning between the solution and polymeric film, mass transfer of dissolved CPT through the film to ultimately reach the bulk dissolution fluid. A SR CPT bead formulation that has potential for further development and optimisation for scaled-up production using RSM approaches and Design of Experiments such as CCD or Box-Behnken has been successfully developed and manufactured using extrusion, spheronisation and coating processes. Assessment of all batches of beads manufactured exhibited satisfactory to good flow properties and demonstrated SR profiles over 12 hours that met USP criteria for SR dosage forms.
- Full Text:
- Date Issued: 2015
- Authors: Mhaka, Farai Arthur
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54712 , vital:26602
- Description: Hypertension has a high mortality rate in developing countries such as South Africa. Although the prevention and control of hypertension is a health priority, efforts to decrease the global burden of hypertension and improve control over the condition are inadequate. The use of angiotensin converting enzyme (ACE) inhibitors such as captopril (CPT) have been effective for the management of hypertension when used as first line therapy alone or in combination. Commercially available immediate release dosage forms containing 12.5, 25 and 50 mg of CPT are administered two or three times a day to treat hypertension. CPT degrades in aqueous media with the sulfhydryl functional moiety responsible for adverse effects such as hypersensitivity, taste disturbances and/or presenting with a dry hacking cough. CPT has a short elimination half-life of between 1.6 and 1.9 hours, which means that the compound is a suitable candidate for inclusion in sustained release (SR) dosage forms. Manufacturing a SR dosage form of coated beads for twice daily dosing may reduce the incidence and intensity of undesirable adverse effects, improve the stability of CPT and improve patient adherence. A stability indicating reversed-phase high performance liquid chromatographic (RP-HPLC) method was developed and optimised using a central composite design approach. As part of this approach the interactive effects of input factors, viz. pH, methanol (MeOH) content and column temperature on retention time, were investigated to achieve a separation with well-resolved and symmetrical peaks for CPT and salicylic acid. The method was validated using ICH guidelines and was found to be simple, linear, precise, accurate, selective and rapid for the in vitro quantitation of CPT. The method was successfully applied for the analysis of both commercially available and test formulations. Preformulation studies were undertaken to establish the physical and chemical properties of CPT, excipients and dosage forms to ensure the production of stabile and bioavailable products. Powder blends were assessed for flow properties using angle of repose (AOR), and bulk and tapped density, which were subsequently used to calculate Carr’s Index (CI) and the Hausner ratio (HR). The addition of talc resulted in the most powder blends with AOR, CI and HR that were within a range indicative of satisfactory to good flow properties. The use of talc was necessary to ensure that blending prior to wet granulation and extrusion-spheronisation would produce homogenous powders. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were used for the identification and purity of CPT alone and 1:1 binary mixtures with excipients in an effort to establish if CPT was likely to undergo physical and/or chemical modification during production. The DSC thermograms for all CPT-excipient mixtures revealed the presence of a melting endotherm that was wider, occurring at 110.93 °C (Tpeak for pure CPT). The characteristic peaks for specific functional groups were present in the FT-IR spectra for powder mixtures, indicating the absence of incompatibilities. Dialysis studies were used to investigate if the ammonium oleate present in Surelease® E-7-19010 interacted with CPT. The results suggests that an interaction between CPT and Surelease® E-7-19010 during processing of CPT beads was unlikely to occur. Preliminary investigations reveal that Methocel® K100M, Methocel® E4M, Avicel® PH102, Eudragit® RS PO, Surelease® E-7-19010 and talc are compatible with CPT and could be used for the manufacture of SR CPT beads. CPT beads were manufactured using extrusion-spheronisation and coated using a fluidised bed drier fitted with a Wurster insert. The amount of granulating fluid, coating levels, curing time and formulation composition were varied to achieve CPT release with specific criteria to develop a preliminary formulation. The coated beads met all desired quality attributes in respect of micromeritic and flow properties, content uniformity and friability. Response Surface Methodology was used to further optimise the SR CPT formulation. The Plackett-Burman design was used for this process to produce an SR dosage form with desirable quality attributes achieved by altering formulation composition, extrusion-spheronisation variables and coating parameters. ANOVA data revealed significant responses for yield, aspect ratio, sphericity, coating efficiency and cumulative percent CPT released at 2 and 12 hours. Formulations in which the high molecular weight HPMC were used in increased concentrations resulted in the formation of a sticky wet mass and extrudate, resulting in a decrease in yield. The application of a permeable, but insoluble Surelease® coat onto the surface of the beads formed a barrier that complements the activity of the hydrophilic matrix in preventing rapid dissolution and retarding the release of CPT from the beads. The amount of CPT released over 12 hours revealed that increasing the Methocel® K100M content entrapped CPT and retained it more efficiently in the hydrated matrix, resulting in a slow rate of CPT release. In vitro release data were fitted to a number of models in an attempt to elucidate mechanistic aspects of transport processes specific to CPT from the coated bead formulations. The results of fitting data from optimised batches revealed that the goodness of fit based on the adjusted correlation coefficient ranged between 0.953 and 0.976 for the Higuchi model, indicating that diffusion is a predominant factor that controls CPT release from the coated beads. The results of fitting data to the Korsmeyer-Peppas model suggest that the mechanism of CPT release includes transport of the dissolution medium from the vessel reservoir into the core of the bead due to osmotic potential, dissolution of CPT, mass transfer of the dissolved CPT within the core, partitioning between the solution and polymeric film, mass transfer of dissolved CPT through the film to ultimately reach the bulk dissolution fluid. A SR CPT bead formulation that has potential for further development and optimisation for scaled-up production using RSM approaches and Design of Experiments such as CCD or Box-Behnken has been successfully developed and manufactured using extrusion, spheronisation and coating processes. Assessment of all batches of beads manufactured exhibited satisfactory to good flow properties and demonstrated SR profiles over 12 hours that met USP criteria for SR dosage forms.
- Full Text:
- Date Issued: 2015
Fabrication and characterization of ciprofloxacin loaded niosomes for transtympanic delivery
- Authors: Mhlanga, Asavela
- Date: 2022-04-06
- Subjects: Drug delivery systems , Liposomes , Ciprofloxacin , Quinolone antibacterial agents , Drug carriers (Pharmacy) , Drug stability , Lamellarity , Niosomes
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290715 , vital:56777
- Description: Ciprofloxacin (CPH) is a broad-spectrum antibiotic used to treat bone, joint, and skin infections. It is commercially available as an extended-release tablet and as a cream dosage form. CPH is a bactericidal active pharmaceutical ingredient (API) of the fluoroquinolone drug class. It inhibits deoxyribonucleic acid (DNA) replication by inhibiting bacterial DNA topoisomerase and DNA gyrase enzymes. Common adverse effects include nausea, vomiting, unusual fatigue, pale skin, and may increase the risk of tendinitis, which could be a major concern. CPH is, according to the Biopharmaceutics Classification System (BCS), classified as a BCS class IV drug exhibiting low oral bioavailability, low solubility, and intestinal permeability. CPH was chosen as a good candidate for the study because of its stability in solutions, its low molecular weight (331.4 g/mol), and its moderate lipophilicity (log P = 0.28) [16]. The use of conventional ear drops in the ear is effective, avoids hepatic first metabolism and extensive protein binding and may reduce adverse effects as a low dose may be used to achieve a therapeutic effect. However, conventional ear drops and oral antibiotics have a long onset of action and have to be taken/applied in short intervals. For convenience and assurance of a long residence time in the ear, CPH may be delivered by using a niosomal formulation, a liquid at room temperature, to allow administration into the ear without the need to constantly apply the ear drops for long periods of time. A simple, rapid, precise, accurate, reproducible, and specific reversed-phase high-performance liquid chromatography (RP-HPLC) method using ultraviolet (UV) detection for the quantitation of CPH was developed and optimized using a central composite design (CCD). The method was validated using International Conference on Harmonisation (ICH) guidelines and was found to be linear, precise, accurate, and specific for the analysis of CPH. Since the method is specific, it was used to quantify CPH in commercial and experimental formulations and monitor CPH released during in-vitro release testing. The compatibility of CPH and potential excipients was investigated during preformulation studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) to identify and select suitable excipients for use during formulation development activities. No apparent interactions were evident between CPH, and the excipients tested. The probe sonication method was used to manufacture CPH loaded niosomes using different surfactants/surfactant combinations, and a combination of Tween® 80: sodium lauryl sulfate (SLS) was found to be the best composition in terms of both entrapment efficiency and Zeta potential. The limits for the independent input variables used for the manufacture included amplitude, sonication time, and amount of cholesterol were determined. Design of experiments (DOE) was used to design the study. The input variables investigated included amplitude, amount of cholesterol, and sonication time. The output or responses monitored included Zeta potential, vesicle size, polydispersity index (PDI), and entrapment efficiency. Non-ionic surfactant systems are predominantly stabilized by steric stabilization, and there is only a minor electrostatic element from adsorbed hydroxyl ions. With the inclusion of SLS it is to be expected that Zeta potential will be a contributing factor. DOE using Box-Behnken design (BBD) and response surface methodology (RSM) in addition to Artificial Neural Networks (ANN) were used for the optimization of the formulation. The optimized formulation had a composition of 1 g cholesterol, 1 g of Tween® 80, 1 g of SLS and was prepared at an amplitude of 11.294 % with a sonication time of 3.304 minutes. The formulation exhibited zero-order release kinetics and had an average pH of 7.45. The formulation was stored at 4 ℃ and 25 ℃ and was assessed for vesicle size, entrapment efficiency, Zeta potential, colour, lamellarity, and PDI every 7 days for 4 weeks. The lead formulation stored at 4 ℃ was more stable than the formulation at 25 ℃ in terms of entrapment efficiency, PDI and vesicle size during the 4-week period. CPH loaded niosomes for transtympanic delivery in the treatment of otitis media were developed and optimized. The technology exhibits sustained release of CPH and has the potential for further development and optimization. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Mhlanga, Asavela
- Date: 2022-04-06
- Subjects: Drug delivery systems , Liposomes , Ciprofloxacin , Quinolone antibacterial agents , Drug carriers (Pharmacy) , Drug stability , Lamellarity , Niosomes
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290715 , vital:56777
- Description: Ciprofloxacin (CPH) is a broad-spectrum antibiotic used to treat bone, joint, and skin infections. It is commercially available as an extended-release tablet and as a cream dosage form. CPH is a bactericidal active pharmaceutical ingredient (API) of the fluoroquinolone drug class. It inhibits deoxyribonucleic acid (DNA) replication by inhibiting bacterial DNA topoisomerase and DNA gyrase enzymes. Common adverse effects include nausea, vomiting, unusual fatigue, pale skin, and may increase the risk of tendinitis, which could be a major concern. CPH is, according to the Biopharmaceutics Classification System (BCS), classified as a BCS class IV drug exhibiting low oral bioavailability, low solubility, and intestinal permeability. CPH was chosen as a good candidate for the study because of its stability in solutions, its low molecular weight (331.4 g/mol), and its moderate lipophilicity (log P = 0.28) [16]. The use of conventional ear drops in the ear is effective, avoids hepatic first metabolism and extensive protein binding and may reduce adverse effects as a low dose may be used to achieve a therapeutic effect. However, conventional ear drops and oral antibiotics have a long onset of action and have to be taken/applied in short intervals. For convenience and assurance of a long residence time in the ear, CPH may be delivered by using a niosomal formulation, a liquid at room temperature, to allow administration into the ear without the need to constantly apply the ear drops for long periods of time. A simple, rapid, precise, accurate, reproducible, and specific reversed-phase high-performance liquid chromatography (RP-HPLC) method using ultraviolet (UV) detection for the quantitation of CPH was developed and optimized using a central composite design (CCD). The method was validated using International Conference on Harmonisation (ICH) guidelines and was found to be linear, precise, accurate, and specific for the analysis of CPH. Since the method is specific, it was used to quantify CPH in commercial and experimental formulations and monitor CPH released during in-vitro release testing. The compatibility of CPH and potential excipients was investigated during preformulation studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) to identify and select suitable excipients for use during formulation development activities. No apparent interactions were evident between CPH, and the excipients tested. The probe sonication method was used to manufacture CPH loaded niosomes using different surfactants/surfactant combinations, and a combination of Tween® 80: sodium lauryl sulfate (SLS) was found to be the best composition in terms of both entrapment efficiency and Zeta potential. The limits for the independent input variables used for the manufacture included amplitude, sonication time, and amount of cholesterol were determined. Design of experiments (DOE) was used to design the study. The input variables investigated included amplitude, amount of cholesterol, and sonication time. The output or responses monitored included Zeta potential, vesicle size, polydispersity index (PDI), and entrapment efficiency. Non-ionic surfactant systems are predominantly stabilized by steric stabilization, and there is only a minor electrostatic element from adsorbed hydroxyl ions. With the inclusion of SLS it is to be expected that Zeta potential will be a contributing factor. DOE using Box-Behnken design (BBD) and response surface methodology (RSM) in addition to Artificial Neural Networks (ANN) were used for the optimization of the formulation. The optimized formulation had a composition of 1 g cholesterol, 1 g of Tween® 80, 1 g of SLS and was prepared at an amplitude of 11.294 % with a sonication time of 3.304 minutes. The formulation exhibited zero-order release kinetics and had an average pH of 7.45. The formulation was stored at 4 ℃ and 25 ℃ and was assessed for vesicle size, entrapment efficiency, Zeta potential, colour, lamellarity, and PDI every 7 days for 4 weeks. The lead formulation stored at 4 ℃ was more stable than the formulation at 25 ℃ in terms of entrapment efficiency, PDI and vesicle size during the 4-week period. CPH loaded niosomes for transtympanic delivery in the treatment of otitis media were developed and optimized. The technology exhibits sustained release of CPH and has the potential for further development and optimization. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
Adreno-active substances and the pineal gland
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
A study of plocamium corallorhiza secondary metabolites and their biological activity
- Authors: Mkwananzi, Henry Bayanda
- Date: 2005
- Subjects: Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3841 , http://hdl.handle.net/10962/d1007666 , Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Description: Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.
- Full Text:
- Date Issued: 2005
- Authors: Mkwananzi, Henry Bayanda
- Date: 2005
- Subjects: Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3841 , http://hdl.handle.net/10962/d1007666 , Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Description: Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.
- Full Text:
- Date Issued: 2005
African traditional medicines-antiretroviral drug interactions: the effect of African potato (Hypoxis hemerocallidea) on the pharmacokinetics of efavirenz in humans
- Authors: Mogatle, Seloi
- Date: 2009
- Subjects: Potatoes -- Africa Potatoes -- Therapeutic use Medicinal plants Traditional medicine AIDS (Disease) -- Treatment HIV infections -- Drug therapy Drug interactions Antiretroviral agents Pharmacokinetics Hypoxidaceae -- Therapeutic use High performance liquid chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3773 , http://hdl.handle.net/10962/d1003251
- Description: African Potato (Hypoxis hemerocallidea), (AP) is an African traditional medicine (TM) that is commonly used for various nutritional/medicinal purposes and also by people infected with the human immuno deficiency virus HIV and AIDS patients as an immune booster. The use of AP has also been recommended by the former Minister of Health of South Africa for use by HIV positive people. The main phytochemical component of AP is a norlignan glucoside, hypoxoside, and other relatively minor components have also been reported. A recent in vitro study reported the effects of AP extracts, hypoxoside and rooperol (the metabolite of hypoxoside) on human metabolic enzymes such as the cytochrome P450 (CYP450) group of enzymes and also on the transporter protein, p-glycoprotein (P-gp). This research focussed on investigating the clinical significance of those in vitro effects on the pharmacokinetics of efavirenz (EFV) in humans. EFV was chosen as the substrate drug because it is in first-line regimen of treatment of HIV/AIDS in South Africa, and also has been reported to be a substrate for the specific CYP isozymes, 3A4 and 2B6, in common with APs metabolic involvement with 3A4. A high performance liquid chromatography method with ultra-violet detection (HPLC-UV) for the quantitative determination of EFV in plasma was developed and successfully validated according to international standards with good reproducibility, accuracy, recovery, linear response and requisite sensitivity. The preparation of the plasma samples for analysis was effected by using a simple and rapid precipitation method, and the mobile phase consisted of readily available solvents. EFV in plasma samples was found to be stable under the relevant storage conditions studied. The oral dose of AP, administered as a freshly prepared traditional decoction, was standardised based on the hypoxoside content, and the quality of all the AP decoctions was analysed immediately prior to administration, using a validated HPLC-UV method. A single dose, two-phase sequential study was conducted over a period of 31 days in 10 healthy volunteers. The clinical study was approved by the Rhodes University Ethical Standards Committee, and all the participants agreed to the conditions of the study by giving their informed consent. On day 1 of the study, human subjects were administered a 600 mg EFV tablet and blood samples were collected before dosing and at various intervals over a period of 48 hr post dosing. From day 16, a traditionally prepared AP decoction was administered daily at a standardized dose of 15 mg/kg/day per subject until day 30. On day 29, volunteers were administered a single 600 mg dose of EFV as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at -80 ºC until assayed. Geometric mean ratios of relevant pharmacokinetic parameters, Cmax (maximum plasma concentration achieved following dosing) and AUC0-48 (area under the curve of a plot of drug plasma concentrations versus time representing the extent of absorption) of EFV before and after co-administration of 14 successive daily doses of AP were compared and evaluated to determine whether an interaction had occurred. All subjects completed the study and the geometric mean ratios of Cmax and AUC0-48 were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81-120.14% and 89.04-118.80%, respectively. Whereas the acceptance criteria for the ratios of the AUCs fell within the preset 90% CIs indicating no interaction, the Cmax ratios fell outside the limits. Although the protocol was developed in accordance with the United States of America Food & Drug Administration’s Guidance for Drug Interactions, a priori stating that both criteria need to fall within the acceptance limits to indicate no interaction, an argument is presented to waive the Cmax requirement for the declaration of an interaction. As a result, the pharmacokinetic data generated during this study indicated that the effect of AP on the pharmacokinetics of EFV is not clinically significant. Hence, co-administration of AP is unlikely to affect the clinical use of EFV. In summary the objectives of this project were: 1. To develop and validate a suitable HPLC-UV method for the quantitative determination of EFV in plasma. 2. To perform a mini-validation of the determination of hypoxoside for use as a marker in the quality control and standardisation of AP decoctions. 3. To conduct a clinical interaction study in order to determine whether AP affects the pharmacokinetics of EFV following concurrent administration. 4. To apply the validated HPLC-UV method to determine plasma concentrations of EFV in plasma of human subjects. 5. To use appropriate statistical methods and treatments such as a non-compartmental pharmacokinetic analysis to determine the occurrence of an interaction.
- Full Text:
- Date Issued: 2009
- Authors: Mogatle, Seloi
- Date: 2009
- Subjects: Potatoes -- Africa Potatoes -- Therapeutic use Medicinal plants Traditional medicine AIDS (Disease) -- Treatment HIV infections -- Drug therapy Drug interactions Antiretroviral agents Pharmacokinetics Hypoxidaceae -- Therapeutic use High performance liquid chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3773 , http://hdl.handle.net/10962/d1003251
- Description: African Potato (Hypoxis hemerocallidea), (AP) is an African traditional medicine (TM) that is commonly used for various nutritional/medicinal purposes and also by people infected with the human immuno deficiency virus HIV and AIDS patients as an immune booster. The use of AP has also been recommended by the former Minister of Health of South Africa for use by HIV positive people. The main phytochemical component of AP is a norlignan glucoside, hypoxoside, and other relatively minor components have also been reported. A recent in vitro study reported the effects of AP extracts, hypoxoside and rooperol (the metabolite of hypoxoside) on human metabolic enzymes such as the cytochrome P450 (CYP450) group of enzymes and also on the transporter protein, p-glycoprotein (P-gp). This research focussed on investigating the clinical significance of those in vitro effects on the pharmacokinetics of efavirenz (EFV) in humans. EFV was chosen as the substrate drug because it is in first-line regimen of treatment of HIV/AIDS in South Africa, and also has been reported to be a substrate for the specific CYP isozymes, 3A4 and 2B6, in common with APs metabolic involvement with 3A4. A high performance liquid chromatography method with ultra-violet detection (HPLC-UV) for the quantitative determination of EFV in plasma was developed and successfully validated according to international standards with good reproducibility, accuracy, recovery, linear response and requisite sensitivity. The preparation of the plasma samples for analysis was effected by using a simple and rapid precipitation method, and the mobile phase consisted of readily available solvents. EFV in plasma samples was found to be stable under the relevant storage conditions studied. The oral dose of AP, administered as a freshly prepared traditional decoction, was standardised based on the hypoxoside content, and the quality of all the AP decoctions was analysed immediately prior to administration, using a validated HPLC-UV method. A single dose, two-phase sequential study was conducted over a period of 31 days in 10 healthy volunteers. The clinical study was approved by the Rhodes University Ethical Standards Committee, and all the participants agreed to the conditions of the study by giving their informed consent. On day 1 of the study, human subjects were administered a 600 mg EFV tablet and blood samples were collected before dosing and at various intervals over a period of 48 hr post dosing. From day 16, a traditionally prepared AP decoction was administered daily at a standardized dose of 15 mg/kg/day per subject until day 30. On day 29, volunteers were administered a single 600 mg dose of EFV as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at -80 ºC until assayed. Geometric mean ratios of relevant pharmacokinetic parameters, Cmax (maximum plasma concentration achieved following dosing) and AUC0-48 (area under the curve of a plot of drug plasma concentrations versus time representing the extent of absorption) of EFV before and after co-administration of 14 successive daily doses of AP were compared and evaluated to determine whether an interaction had occurred. All subjects completed the study and the geometric mean ratios of Cmax and AUC0-48 were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81-120.14% and 89.04-118.80%, respectively. Whereas the acceptance criteria for the ratios of the AUCs fell within the preset 90% CIs indicating no interaction, the Cmax ratios fell outside the limits. Although the protocol was developed in accordance with the United States of America Food & Drug Administration’s Guidance for Drug Interactions, a priori stating that both criteria need to fall within the acceptance limits to indicate no interaction, an argument is presented to waive the Cmax requirement for the declaration of an interaction. As a result, the pharmacokinetic data generated during this study indicated that the effect of AP on the pharmacokinetics of EFV is not clinically significant. Hence, co-administration of AP is unlikely to affect the clinical use of EFV. In summary the objectives of this project were: 1. To develop and validate a suitable HPLC-UV method for the quantitative determination of EFV in plasma. 2. To perform a mini-validation of the determination of hypoxoside for use as a marker in the quality control and standardisation of AP decoctions. 3. To conduct a clinical interaction study in order to determine whether AP affects the pharmacokinetics of EFV following concurrent administration. 4. To apply the validated HPLC-UV method to determine plasma concentrations of EFV in plasma of human subjects. 5. To use appropriate statistical methods and treatments such as a non-compartmental pharmacokinetic analysis to determine the occurrence of an interaction.
- Full Text:
- Date Issued: 2009
Development and assessment of azithromycin paediatric suppository formulations
- Authors: Mollel, Happiness
- Date: 2006
- Subjects: Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3774 , http://hdl.handle.net/10962/d1003252 , Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Description: The use of the oral route of administration for the treatment of young children with antibiotics can at times be problematic since, factors such as nausea, vomiting, taste and/or smell, in addition to the challenges associated with the administration of suspensions, may contribute to poor patient compliance. In such cases, the use of the rectal route of administration may be appropriate. Therefore, suppositories containing 250 mg azithromycin (AZI) were manufactured and assessed for potential as an antibiotic suppository dosage form. Suppositories, containing AZI dihydrate were manufactured by the fusion method, using different grades of PEG, Witepsol® and Suppocire® bases. The rate and extent of AZI release was evaluated using USP apparatus I, and samples were analyzed using a validated HPLC method. Differences in the rate and extent of AZI release were observed with the greatest amount of AZI being released from PEG formulations. The rate and extent of AZI release from formulations manufactured using fatty bases were influenced by physicochemical properties, such as melting rate and hydroxyl value, of the bases. In addition drug partitioning appeared to favor the lipid phase and had a negative impact on AZI release characteristics. Two different formulation approaches were used in an attempt to increase the rate and extent of AZI release from fatty base formulations. The use of surfactants significantly increased AZI release from formulations manufactured with fatty bases with high hydroxyl values. The use of urea or Povidone K25 in combination with AZI as a physical mixture or solid dispersion did not increase the rate and extent of AZI release from the fatty suppositories, to any significant extent. The mechanism of drug release was evaluated using several mathematical models, including the Higuchi, Korsmeyer- eppas, Zero and, First order models. In addition, in vitro dissolution profiles were characterized by the difference and similarity factors, f1 and f2 and by use of the Gohel similarity factor, Sd. AZI release kinetics were best described by the Higuchi and Korsmeyer-Peppas models and the values of the release exponent, n, revealed that drug release was a consequence of the combined effects of AZI diffusion, rate of melting of the base and partitioning of the drug which can be considered to be anomalous release.
- Full Text:
- Date Issued: 2006
- Authors: Mollel, Happiness
- Date: 2006
- Subjects: Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3774 , http://hdl.handle.net/10962/d1003252 , Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Description: The use of the oral route of administration for the treatment of young children with antibiotics can at times be problematic since, factors such as nausea, vomiting, taste and/or smell, in addition to the challenges associated with the administration of suspensions, may contribute to poor patient compliance. In such cases, the use of the rectal route of administration may be appropriate. Therefore, suppositories containing 250 mg azithromycin (AZI) were manufactured and assessed for potential as an antibiotic suppository dosage form. Suppositories, containing AZI dihydrate were manufactured by the fusion method, using different grades of PEG, Witepsol® and Suppocire® bases. The rate and extent of AZI release was evaluated using USP apparatus I, and samples were analyzed using a validated HPLC method. Differences in the rate and extent of AZI release were observed with the greatest amount of AZI being released from PEG formulations. The rate and extent of AZI release from formulations manufactured using fatty bases were influenced by physicochemical properties, such as melting rate and hydroxyl value, of the bases. In addition drug partitioning appeared to favor the lipid phase and had a negative impact on AZI release characteristics. Two different formulation approaches were used in an attempt to increase the rate and extent of AZI release from fatty base formulations. The use of surfactants significantly increased AZI release from formulations manufactured with fatty bases with high hydroxyl values. The use of urea or Povidone K25 in combination with AZI as a physical mixture or solid dispersion did not increase the rate and extent of AZI release from the fatty suppositories, to any significant extent. The mechanism of drug release was evaluated using several mathematical models, including the Higuchi, Korsmeyer- eppas, Zero and, First order models. In addition, in vitro dissolution profiles were characterized by the difference and similarity factors, f1 and f2 and by use of the Gohel similarity factor, Sd. AZI release kinetics were best described by the Higuchi and Korsmeyer-Peppas models and the values of the release exponent, n, revealed that drug release was a consequence of the combined effects of AZI diffusion, rate of melting of the base and partitioning of the drug which can be considered to be anomalous release.
- Full Text:
- Date Issued: 2006
Effect of anticonvulsant agents on pineal gland indole metabolism
- Authors: Morton, Dougal John
- Date: 1983
- Subjects: Pineal gland -- Metabolism Anticonvulsants
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3844 , http://hdl.handle.net/10962/d1009518
- Description: Preface: The general indications that the pineal gland might be involved in homeostasis, and more specifically the evidence suggesting a role in amelioration of seizure states warranted further investigation . No reports had examined a possible link between anticonvulsant drug administration and pineal gland function, and few enabled any type of presumption to be made as to possible effects. This study was an attempt to evaluate in which ways anticonvulsant drugs might alter pineal gland indole metabolism, with a view to increasing understanding of the role of the pineal in modulation of epileptic discharges. In order to make the study as meaningful as possible extensive preliminary investigations were necessary. Pharmacokinetic determinations gave an indication of tissue concentrations of the drugs, which could then be related to observed effects. As far as possible, where existing information was lacking, the catalytic behaviour of the various enzymes was characterised in order to explain any observed effects at a molecular level. An attempt was also made to characterise the regulatory mechanisms controlling indole metabolism, again in order to define the pharmacological effects exerted by the drugs used. The complexity of the system made it impossible to suggest a single uniform regulatory hypothesis, although some significant observations were made. Finally, the studies involving the anticonvulsant drugs were conducted on intact animals, isolated organs and individual enzymes in an attempt to determine whether the observed effects were occuring at a molecular, local or central level.
- Full Text:
- Date Issued: 1983
- Authors: Morton, Dougal John
- Date: 1983
- Subjects: Pineal gland -- Metabolism Anticonvulsants
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3844 , http://hdl.handle.net/10962/d1009518
- Description: Preface: The general indications that the pineal gland might be involved in homeostasis, and more specifically the evidence suggesting a role in amelioration of seizure states warranted further investigation . No reports had examined a possible link between anticonvulsant drug administration and pineal gland function, and few enabled any type of presumption to be made as to possible effects. This study was an attempt to evaluate in which ways anticonvulsant drugs might alter pineal gland indole metabolism, with a view to increasing understanding of the role of the pineal in modulation of epileptic discharges. In order to make the study as meaningful as possible extensive preliminary investigations were necessary. Pharmacokinetic determinations gave an indication of tissue concentrations of the drugs, which could then be related to observed effects. As far as possible, where existing information was lacking, the catalytic behaviour of the various enzymes was characterised in order to explain any observed effects at a molecular level. An attempt was also made to characterise the regulatory mechanisms controlling indole metabolism, again in order to define the pharmacological effects exerted by the drugs used. The complexity of the system made it impossible to suggest a single uniform regulatory hypothesis, although some significant observations were made. Finally, the studies involving the anticonvulsant drugs were conducted on intact animals, isolated organs and individual enzymes in an attempt to determine whether the observed effects were occuring at a molecular, local or central level.
- Full Text:
- Date Issued: 1983
Development and assessment of rifampicin loaded self-microemulsifying drug delivery systems
- Authors: Mphaphuli, Mashudu Theodore
- Date: 2021-04
- Subjects: To be added
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/178503 , vital:42945
- Description: Access restricted until April 2023. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-04
- Authors: Mphaphuli, Mashudu Theodore
- Date: 2021-04
- Subjects: To be added
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/178503 , vital:42945
- Description: Access restricted until April 2023. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-04
Comparison of the neuroprotective potential of theanine and minocycline
- Authors: Mpofu, Tariro Ann-Maureen
- Date: 2010 , 2010-09-20
- Subjects: Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3775 , http://hdl.handle.net/10962/d1003253 , Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
- Description: Stroke is one of the most common causes of disability and death worldwide. The most commonly experienced stroke in the clinical setting is focal ischaemia in which the middle cerebral artery (MCA) is occluded and leads to a complex series of various pathophysiological pathways that ultimately lead to neuronal cell death. Several studies have been conducted on various therapeutic agents in the search for a neuroprotective drug and various animal models have been used to carry out this research. While theanine, a component of green tea and minocycline, a tetracycline antibiotic, have been shown to possess some neuroprotective properties, the mechanisms by which these two agents carry out these effects still remains unclear. The objectives of this study were to investigate the mechanisms by which these drugs carry out these neuroprotective effects and their neuroprotective ability in a MCA occlusion model of focal ischaemia. Ischaemia leads to oxidative stress due to the imbalance of free radicals and the endogenous antioxidant defence system. An antioxidant assay using the stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH●) radical was used to assess the antiradical properties of each drug. It was found that minocycline showed superior antioxidant activity in vitro when compared to theanine. Further studies on the drugs‟ ability to attenuate the Fenton reaction (in which iron catalyses the formation of reactive species) were elucidated using electrochemical analysis, UV/VIS studies, ferrozine and ferritin assays. It was found that minocycline, in contrast to theanine, was able to bind to iron ions and thus potentially prevent the participation of iron in metal catalysed radical reaction. The antioxidant activity of both drugs was further investigated by assessing their effect on cyanide-induced superoxide generation and quinolinic acid (QA)-induced lipid peroxidation (LP). Experimental evidence shows that both drugs had no significant effect on the generation of superoxide in vitro and that there was a significant decrease in LP for minocycline in vitro and theanine in vivo. The metal binding and antioxidant properties were postulated to be a possible mechanism through which these agents reduced lipid peroxidation. A study was conducted to determine the effects of the drugs on the biosynthesis of the neurotoxin, QA and it was found that minocycline increases the levels of holoenzyme activity of tryptophan-2, 3-dioxygenase (TDO) in vitro and that theanine reduces the levels of the same enzyme in vivo after treatment for 10 days. TDO is the enzyme that converts tryptophan to other products that enable enzymatic activity to change it to QA. Minocycline was thought to bring about this effect as it has been shown from preceding experimental studies that it is an effective reducing agent. Theanine on the other hand is hypothesised to bring about a reduction in holoenzyme activity by changing the binding of tryptophan to the enzyme or affecting the radicals that participate in the enzymatic degradation of tryptophan. A focal ischaemic model of stroke was induced by occluding the MCA. Histological examination of the hippocampus post -ischaemia shows a reduction in the size of the infarct after pre-treatment with minocycline only. A further study into the effects of the drugs on the generation of superoxide and on the levels of the endogenous glutathione after a stroke was carried out. Pre-treatment of the animals with either theanine or minocycline showed no significant effects on the generation of the radical species or of the endogenous antioxidant which ruled out these as a mechanism of neuroprotection of both drugs, post-ischaemia.The findings of this study provide novel information on the possible mechanisms by which both theanine and minocycline act to bring about neuroprotection. In particular in this study, pre-treatment with minocycline has shown promise in the focal ischaemic model of stroke.
- Full Text:
- Date Issued: 2010
- Authors: Mpofu, Tariro Ann-Maureen
- Date: 2010 , 2010-09-20
- Subjects: Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3775 , http://hdl.handle.net/10962/d1003253 , Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
- Description: Stroke is one of the most common causes of disability and death worldwide. The most commonly experienced stroke in the clinical setting is focal ischaemia in which the middle cerebral artery (MCA) is occluded and leads to a complex series of various pathophysiological pathways that ultimately lead to neuronal cell death. Several studies have been conducted on various therapeutic agents in the search for a neuroprotective drug and various animal models have been used to carry out this research. While theanine, a component of green tea and minocycline, a tetracycline antibiotic, have been shown to possess some neuroprotective properties, the mechanisms by which these two agents carry out these effects still remains unclear. The objectives of this study were to investigate the mechanisms by which these drugs carry out these neuroprotective effects and their neuroprotective ability in a MCA occlusion model of focal ischaemia. Ischaemia leads to oxidative stress due to the imbalance of free radicals and the endogenous antioxidant defence system. An antioxidant assay using the stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH●) radical was used to assess the antiradical properties of each drug. It was found that minocycline showed superior antioxidant activity in vitro when compared to theanine. Further studies on the drugs‟ ability to attenuate the Fenton reaction (in which iron catalyses the formation of reactive species) were elucidated using electrochemical analysis, UV/VIS studies, ferrozine and ferritin assays. It was found that minocycline, in contrast to theanine, was able to bind to iron ions and thus potentially prevent the participation of iron in metal catalysed radical reaction. The antioxidant activity of both drugs was further investigated by assessing their effect on cyanide-induced superoxide generation and quinolinic acid (QA)-induced lipid peroxidation (LP). Experimental evidence shows that both drugs had no significant effect on the generation of superoxide in vitro and that there was a significant decrease in LP for minocycline in vitro and theanine in vivo. The metal binding and antioxidant properties were postulated to be a possible mechanism through which these agents reduced lipid peroxidation. A study was conducted to determine the effects of the drugs on the biosynthesis of the neurotoxin, QA and it was found that minocycline increases the levels of holoenzyme activity of tryptophan-2, 3-dioxygenase (TDO) in vitro and that theanine reduces the levels of the same enzyme in vivo after treatment for 10 days. TDO is the enzyme that converts tryptophan to other products that enable enzymatic activity to change it to QA. Minocycline was thought to bring about this effect as it has been shown from preceding experimental studies that it is an effective reducing agent. Theanine on the other hand is hypothesised to bring about a reduction in holoenzyme activity by changing the binding of tryptophan to the enzyme or affecting the radicals that participate in the enzymatic degradation of tryptophan. A focal ischaemic model of stroke was induced by occluding the MCA. Histological examination of the hippocampus post -ischaemia shows a reduction in the size of the infarct after pre-treatment with minocycline only. A further study into the effects of the drugs on the generation of superoxide and on the levels of the endogenous glutathione after a stroke was carried out. Pre-treatment of the animals with either theanine or minocycline showed no significant effects on the generation of the radical species or of the endogenous antioxidant which ruled out these as a mechanism of neuroprotection of both drugs, post-ischaemia.The findings of this study provide novel information on the possible mechanisms by which both theanine and minocycline act to bring about neuroprotection. In particular in this study, pre-treatment with minocycline has shown promise in the focal ischaemic model of stroke.
- Full Text:
- Date Issued: 2010