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
A medicinal chemistry study in nitrogen containing heterocycles
- Authors: Lunga, Mayibongwe Junior
- Date: 2018
- Subjects: Indole , Tetrazoles , Antimalarials , Heat shock proteins , Plasmodium falciparum
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63521 , vital:28430
- Description: Heterocyclic structures have found extensive utility in the field of medicinal chemistry, as prominent regions of pharmacophores resulting in numerous drug treatments for many diseases. Accordingly, in this project we explored the respective antimalarial and anticancer activity exhibited by compounds featuring nitrogen containing indole and tetrazole heterocycles respectively. This thesis therefore comprises of two distinct parts. Part 1. Following the development of resistance towards traditional antimalarial therapy such as chloroquine and emerging resistance towards artemisinin combination therapies, the WHO reported the urgent need for new, effective drugs and identification of new drug targets to combat the Plasmodium falciparum parasite. In 2015 the parasite was the cause of 429 000 deaths, the majority occurring in the sub-Saharan region of Africa. This highlights the failing effectiveness of vector control strategies, reiterating the need to develop alternative control and treatment strategies. In response to this need we wanted to expand and further describe the SAR of the indole based series, indolyl-3-ethanone-α- thioethers, previously synthesized in our laboratory. These compounds were found to exhibit antimalarial activity with compounds 2.26 and 2.27 exhibiting activity against P. falciparum 3D7 in the nanomolar range. Based on these compounds we synthesized compounds 3.21 and 3.24 – 3.32 following a three step reaction pathway. Our results in this study, indicate that compound 3.28, a pnitrothiophenol analogue of 2.27 was the most active of the compounds we synthesized and furthermore was superior in activity against Plasmodium compared to 2.27. This result indicated that the presence of p-NO2 is important in enhancing anti-plasmodial activity. Comparing compounds 3.25 and 3.26 with an oxygen on the ether bridge to compounds 3.29 and 3.30 with a sulfur, we observed an increase in hydrophilicity coupled to a decrease in anti-plasmodial activity in the compounds, thus, highlighting the importance of sulfur for enhanced activity. Furthermore, we investigated bioisosteric replacement of the 5-chloro substituent present in hit compounds 2.27 and 3.28, with an electron withdrawing nitrile (3.27) and electron donating methyl (3.29) and methoxy (3.31) substituents. These substituents decreased anti-plasmodial activity, confirming that a chlorine substituent is optimal for biological activity. This study furthered our understanding of the SAR of indolyl-3-ethanone-α- thioethers for the development of potent anti-plasmodial lead compounds. Part 2. Triple negative breast cancer (TNBC), which disproportionately affects women of sub-Saharan Africa, is unresponsive to hormone-based therapies. This emergence presents a population of patients devoid of effective drug treatment, signaling the urgent need to develop new effective therapies with novel drug targets. Therefore, we identified our target in TNBC cells as the protein-protein interaction between the co-chaperones HOP and HSP90. We reasoned that a disruption of this interaction would ultimately result in cancer cell death via the degradation of essential oncogenic client proteins. Following a fragment screening campaign, which identified several acid and tetrazole containing hits (4.56 – 4.58) which bound to HOP, with low anticancer activity, we sought to develop synthetic methodology to elaborate our fragment hits synthesizing tetrazole containing fragments to target TNBC cell lines. We therefore proceeded to synthesize a range of multi substituted fragments (4.59 – 4.63), utilizing a nitrile (4.66) to access tetrazoles via 1,3-cycloaddition and an acid by nitrile hydrolysis. We successfully synthesized the tetrazole and acid fragments which are currently undergoing characterization for activity against TNBC. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Date Issued: 2018
- Authors: Lunga, Mayibongwe Junior
- Date: 2018
- Subjects: Indole , Tetrazoles , Antimalarials , Heat shock proteins , Plasmodium falciparum
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63521 , vital:28430
- Description: Heterocyclic structures have found extensive utility in the field of medicinal chemistry, as prominent regions of pharmacophores resulting in numerous drug treatments for many diseases. Accordingly, in this project we explored the respective antimalarial and anticancer activity exhibited by compounds featuring nitrogen containing indole and tetrazole heterocycles respectively. This thesis therefore comprises of two distinct parts. Part 1. Following the development of resistance towards traditional antimalarial therapy such as chloroquine and emerging resistance towards artemisinin combination therapies, the WHO reported the urgent need for new, effective drugs and identification of new drug targets to combat the Plasmodium falciparum parasite. In 2015 the parasite was the cause of 429 000 deaths, the majority occurring in the sub-Saharan region of Africa. This highlights the failing effectiveness of vector control strategies, reiterating the need to develop alternative control and treatment strategies. In response to this need we wanted to expand and further describe the SAR of the indole based series, indolyl-3-ethanone-α- thioethers, previously synthesized in our laboratory. These compounds were found to exhibit antimalarial activity with compounds 2.26 and 2.27 exhibiting activity against P. falciparum 3D7 in the nanomolar range. Based on these compounds we synthesized compounds 3.21 and 3.24 – 3.32 following a three step reaction pathway. Our results in this study, indicate that compound 3.28, a pnitrothiophenol analogue of 2.27 was the most active of the compounds we synthesized and furthermore was superior in activity against Plasmodium compared to 2.27. This result indicated that the presence of p-NO2 is important in enhancing anti-plasmodial activity. Comparing compounds 3.25 and 3.26 with an oxygen on the ether bridge to compounds 3.29 and 3.30 with a sulfur, we observed an increase in hydrophilicity coupled to a decrease in anti-plasmodial activity in the compounds, thus, highlighting the importance of sulfur for enhanced activity. Furthermore, we investigated bioisosteric replacement of the 5-chloro substituent present in hit compounds 2.27 and 3.28, with an electron withdrawing nitrile (3.27) and electron donating methyl (3.29) and methoxy (3.31) substituents. These substituents decreased anti-plasmodial activity, confirming that a chlorine substituent is optimal for biological activity. This study furthered our understanding of the SAR of indolyl-3-ethanone-α- thioethers for the development of potent anti-plasmodial lead compounds. Part 2. Triple negative breast cancer (TNBC), which disproportionately affects women of sub-Saharan Africa, is unresponsive to hormone-based therapies. This emergence presents a population of patients devoid of effective drug treatment, signaling the urgent need to develop new effective therapies with novel drug targets. Therefore, we identified our target in TNBC cells as the protein-protein interaction between the co-chaperones HOP and HSP90. We reasoned that a disruption of this interaction would ultimately result in cancer cell death via the degradation of essential oncogenic client proteins. Following a fragment screening campaign, which identified several acid and tetrazole containing hits (4.56 – 4.58) which bound to HOP, with low anticancer activity, we sought to develop synthetic methodology to elaborate our fragment hits synthesizing tetrazole containing fragments to target TNBC cell lines. We therefore proceeded to synthesize a range of multi substituted fragments (4.59 – 4.63), utilizing a nitrile (4.66) to access tetrazoles via 1,3-cycloaddition and an acid by nitrile hydrolysis. We successfully synthesized the tetrazole and acid fragments which are currently undergoing characterization for activity against TNBC. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Date Issued: 2018
A novel o/w microemulsion fixed dose combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate: development and characterisation
- Authors: Mabvira, Samantha
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232925 , vital:50038
- Description: Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Mabvira, Samantha
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232925 , vital:50038
- Description: Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
A retrospective study of antimicrobial prescribing practices in paediatric patients at the Mahalapye District Hospital, Central Botswana
- Authors: Nyawera, Angella
- Date: 2022-04-06
- Subjects: Anti-infective agents Botswana Mahalapye , Drug resistance , Pediatrics Botswana Mahalapye , Pediatrics Formulae, receipts, prescriptions , Drugs Prescribing Moral and ethical aspects
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290682 , vital:56774
- Description: Background: The development of antimicrobial resistance (AMR) has been linked to the increased and irrational use of antimicrobial medicines. The aim of this study was to investigate the antimicrobial prescribing practices in the paediatric medical ward at Mahalapye District Hospital (MDH) in Botswana and to determine whether antimicrobial stewardship (AMS) measures were being implemented at the hospital. Methods A cross-sectional, descriptive, mixed methods, observational approach was taken in this study. The study site was the paediatric medical ward (PMW) at MDH. Information about the antimicrobials prescribed for paediatric patients from January 2018 to December 2018 was collected from patients’ information files and compared to national antimicrobial prescribing guidelines to determine prescribers’ adherence. Qualitative semi-structured interviews were conducted with members of staff at MDH to determine whether antimicrobial stewardship (AMS) measures were adopted at the hospital. Results A total of 278 patients were included in this study, 12 of these were admitted twice during the study period. In total 290 admissions were analysed, with 659 antimicrobial medicines prescribed. The most common diagnoses were pneumonia (36.9%), acute gastroenteritis (20.7%), upper respiratory tract infections (3.4%), and bronchiolitis (3.1%). The most prescribed antimicrobials were ampicillin (21.4%), gentamicin (21.2%), and cefotaxime (8.3%). Adherence to guidelines was relatively good, with 82.7% of antimicrobials prescribed for the patients in the study having been prescribed in compliance with the national prescribing guidelines. The semi-structured interviews highlighted the fact that staff knew about AMS and AMR in general, however awareness of an AMS committee at MDH varied. The AMS committee was a multidisciplinary committee, which was a subcommittee of the Drugs and Therapeutics Committee (DTC). Discussion and Conclusion The results suggest that adherence to prescribing guidelines was relatively high compared to other paediatric antimicrobial utilisation studies in African countries. Prescribing of antimicrobial medicines was consistent with other African countries. The long period of time that it takes for microbiological test results to become available means that most prescribers rely on empirical prescribing. The antimicrobial committee is a multidisciplinary committee with defined roles for its members, consistent with international guidelines for implementing an AMS committee at a hospital. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Nyawera, Angella
- Date: 2022-04-06
- Subjects: Anti-infective agents Botswana Mahalapye , Drug resistance , Pediatrics Botswana Mahalapye , Pediatrics Formulae, receipts, prescriptions , Drugs Prescribing Moral and ethical aspects
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/290682 , vital:56774
- Description: Background: The development of antimicrobial resistance (AMR) has been linked to the increased and irrational use of antimicrobial medicines. The aim of this study was to investigate the antimicrobial prescribing practices in the paediatric medical ward at Mahalapye District Hospital (MDH) in Botswana and to determine whether antimicrobial stewardship (AMS) measures were being implemented at the hospital. Methods A cross-sectional, descriptive, mixed methods, observational approach was taken in this study. The study site was the paediatric medical ward (PMW) at MDH. Information about the antimicrobials prescribed for paediatric patients from January 2018 to December 2018 was collected from patients’ information files and compared to national antimicrobial prescribing guidelines to determine prescribers’ adherence. Qualitative semi-structured interviews were conducted with members of staff at MDH to determine whether antimicrobial stewardship (AMS) measures were adopted at the hospital. Results A total of 278 patients were included in this study, 12 of these were admitted twice during the study period. In total 290 admissions were analysed, with 659 antimicrobial medicines prescribed. The most common diagnoses were pneumonia (36.9%), acute gastroenteritis (20.7%), upper respiratory tract infections (3.4%), and bronchiolitis (3.1%). The most prescribed antimicrobials were ampicillin (21.4%), gentamicin (21.2%), and cefotaxime (8.3%). Adherence to guidelines was relatively good, with 82.7% of antimicrobials prescribed for the patients in the study having been prescribed in compliance with the national prescribing guidelines. The semi-structured interviews highlighted the fact that staff knew about AMS and AMR in general, however awareness of an AMS committee at MDH varied. The AMS committee was a multidisciplinary committee, which was a subcommittee of the Drugs and Therapeutics Committee (DTC). Discussion and Conclusion The results suggest that adherence to prescribing guidelines was relatively high compared to other paediatric antimicrobial utilisation studies in African countries. Prescribing of antimicrobial medicines was consistent with other African countries. The long period of time that it takes for microbiological test results to become available means that most prescribers rely on empirical prescribing. The antimicrobial committee is a multidisciplinary committee with defined roles for its members, consistent with international guidelines for implementing an AMS committee at a hospital. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
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
Adherence to antiretroviral therapy in children in Zimbabwe: a randomized control trial to validate a new self-reported adherence monitoring tool
- Authors: Mugore, Linnetie
- Date: 2014
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54734 , vital:26607
- Description: Background: Among children taking antiretroviral therapy (ART), self-reports have been widely reported to over-estimate adherence levels. Pill count adherence levels are often lower than self-reported levels, with unannounced home pill count adherence being lower than facility based pill count adherence. There is often poor agreement between pill count adherence levels and those measured using other objective adherence measuring methods such as Medication Event Monitoring Systems (MEMS®), which is widely viewed as the gold standard for adherence measurement. Objectives: The aim of this study was to design and evaluate a new self-reported paediatric adherence monitoring tool, assess the feasibility of using pill count methods in monitoring adherence and identify challenges to reporting adherence among children on ART in rural and urban Zimbabwe. Methods A dual centre, superiority, parallel design RCT was conducted to evaluate the newly-developed visually- and verbally-cued „past 10 days‟ tool for the assessment of adherence in children on ART at two sites in Zimbabwe; Harare Central Children‟s Hospital in an urban setting, and Murambinda Mission Hospital, a rural site. Child-caregiver pairs presenting to one of these facilities for the child‟s review of ART and refill of the medication were recruited, signed informed consent obtained, and were randomised for self-reported adherence monitoring into either the experimental group („new 10-day tool‟) or the control group („PACTG-style‟ self-report tool). Data (demographic, socioeconomic, and reported adherence) were collected in individual interviews with child-caregiver pairs. Additional adherence monitoring methods used for both groups included the Morisky-8-Item Medication Adherence Scale (MMAS-8) and a facility based pill count. FGDs were held with groups of caregivers and groups of children ≥13 years of age to understand reasons for non-adherence as well as issues around reporting non-adherence. Superiority testing was conducted by comparing adherent proportions and their confidence intervals (95% CI). Further concurrent validity test was done using the Mann-Whitney U test to evaluate the relationship between the new tool and the MMAS-8 scores. Agreement between the child and caregiver reports of adherence was used as a test of reliability of the new tool using the kappa statistic. Socio-demographic, clinical and care-related factors associated with adherence were identified using reported adherence in both child and caregiver groups in a logistic regression model. Two pill count methods were assessed for feasibility using the proportions of children with complete data for calculating adherence levels, and their CI and a comparison of the two methods, a routinely-used method and one that incorporated the reported residual quantity (RRQ) of medication at last refill. Results : Analysis included 245 child-caregiver pairs, 123 in the experimental group and 122 in the control group. The median age for children was 9 years. In the experimental group, adherence by caregiver and child reports ranged from 94.3% - 98.4% and 78.4% - 96.1%, and those in the control group ranged from 89.2% - 97.5% and 71.2% - 98.1%, respectively. There was no significant difference between adherence levels in the two groups. Adherence levels measured by both the experimental and control tools were found to be associated with MMAS-8 adherence levels (p <0.05). Agreement between child- and caregiver-reported adherence was moderate though significant (kappa; 0.407, p <0.05). Only about half of the children had adequate data to compute pill counts. Proportions adherent at 95% cut-off were 39% by the „routine pill count‟ and 58% by the „Pill count RRQ‟. Being an orphan was associated with child reported-adherence whereas use of non-human reminders, having a maternal relative as a primary caregiver and knowledge of dose frequency, were all associated with caregiver-reported adherence. Major causes of non-adherence mentioned during the FGDs included interference of medication administration times with scheduling of routine socio-economic activities and lack of support from some non-biological caregivers. Reporting of non-adherence appeared to be hampered by perceptions of negative reactions by healthcare workers to these reports and by caregivers being unaware that the child missed some doses. Conclusions: The „new 10-day tool‟ was not shown to be superior to the „PACTG-style tool‟ in detecting non-adherence, however this new tool was found to be a valid and reliable adherence monitoring tool that included a moderately long recall period of 10 days, can be applied without the need for the respondent to remember names of individual medicines in the
- Full Text:
- Date Issued: 2014
- Authors: Mugore, Linnetie
- Date: 2014
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54734 , vital:26607
- Description: Background: Among children taking antiretroviral therapy (ART), self-reports have been widely reported to over-estimate adherence levels. Pill count adherence levels are often lower than self-reported levels, with unannounced home pill count adherence being lower than facility based pill count adherence. There is often poor agreement between pill count adherence levels and those measured using other objective adherence measuring methods such as Medication Event Monitoring Systems (MEMS®), which is widely viewed as the gold standard for adherence measurement. Objectives: The aim of this study was to design and evaluate a new self-reported paediatric adherence monitoring tool, assess the feasibility of using pill count methods in monitoring adherence and identify challenges to reporting adherence among children on ART in rural and urban Zimbabwe. Methods A dual centre, superiority, parallel design RCT was conducted to evaluate the newly-developed visually- and verbally-cued „past 10 days‟ tool for the assessment of adherence in children on ART at two sites in Zimbabwe; Harare Central Children‟s Hospital in an urban setting, and Murambinda Mission Hospital, a rural site. Child-caregiver pairs presenting to one of these facilities for the child‟s review of ART and refill of the medication were recruited, signed informed consent obtained, and were randomised for self-reported adherence monitoring into either the experimental group („new 10-day tool‟) or the control group („PACTG-style‟ self-report tool). Data (demographic, socioeconomic, and reported adherence) were collected in individual interviews with child-caregiver pairs. Additional adherence monitoring methods used for both groups included the Morisky-8-Item Medication Adherence Scale (MMAS-8) and a facility based pill count. FGDs were held with groups of caregivers and groups of children ≥13 years of age to understand reasons for non-adherence as well as issues around reporting non-adherence. Superiority testing was conducted by comparing adherent proportions and their confidence intervals (95% CI). Further concurrent validity test was done using the Mann-Whitney U test to evaluate the relationship between the new tool and the MMAS-8 scores. Agreement between the child and caregiver reports of adherence was used as a test of reliability of the new tool using the kappa statistic. Socio-demographic, clinical and care-related factors associated with adherence were identified using reported adherence in both child and caregiver groups in a logistic regression model. Two pill count methods were assessed for feasibility using the proportions of children with complete data for calculating adherence levels, and their CI and a comparison of the two methods, a routinely-used method and one that incorporated the reported residual quantity (RRQ) of medication at last refill. Results : Analysis included 245 child-caregiver pairs, 123 in the experimental group and 122 in the control group. The median age for children was 9 years. In the experimental group, adherence by caregiver and child reports ranged from 94.3% - 98.4% and 78.4% - 96.1%, and those in the control group ranged from 89.2% - 97.5% and 71.2% - 98.1%, respectively. There was no significant difference between adherence levels in the two groups. Adherence levels measured by both the experimental and control tools were found to be associated with MMAS-8 adherence levels (p <0.05). Agreement between child- and caregiver-reported adherence was moderate though significant (kappa; 0.407, p <0.05). Only about half of the children had adequate data to compute pill counts. Proportions adherent at 95% cut-off were 39% by the „routine pill count‟ and 58% by the „Pill count RRQ‟. Being an orphan was associated with child reported-adherence whereas use of non-human reminders, having a maternal relative as a primary caregiver and knowledge of dose frequency, were all associated with caregiver-reported adherence. Major causes of non-adherence mentioned during the FGDs included interference of medication administration times with scheduling of routine socio-economic activities and lack of support from some non-biological caregivers. Reporting of non-adherence appeared to be hampered by perceptions of negative reactions by healthcare workers to these reports and by caregivers being unaware that the child missed some doses. Conclusions: The „new 10-day tool‟ was not shown to be superior to the „PACTG-style tool‟ in detecting non-adherence, however this new tool was found to be a valid and reliable adherence monitoring tool that included a moderately long recall period of 10 days, can be applied without the need for the respondent to remember names of individual medicines in the
- Full Text:
- Date Issued: 2014
Adolescent pregnancy: a community engaged participatory approach to design and implement an educational intervention
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
- Date Issued: 2014
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
- Date Issued: 2014
An energy, water and disease disaster management module: a technoeconomic feasibility analysis
- Authors: Nicholson, Thomas J
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/65167 , vital:28700
- Description: Intermittent energy and water supply are current challenges faced by many residents in South Africa. South Africa is one of the more water scarce countries in the world; this coupled with the lack of infrastructure makes it challenging to provide every citizen with their right to basic water and sanitation. With millennium development goal 7C not being addressed in many areas, residents experience sub-standard living conditions, which drastically increases the vulnerability of marginalised groups to epidemics. In the sustainable development goals improving sanitation and drinking water has been identified as one of the most effective and least expensive means of reducing fatalities and increasing public health. There is a need for a mobile laboratory that demonstrates power and water self-sufficiency, which is capable of on-site diagnosis and water treatment. The unit will have the ability to perform independent compliance monitoring of municipal water supply, treat inadequate water and provide surplus electricity to surrounding areas. A literature-based study was performed utilizing several scientific databases to identify current methods of power and water production in previous disaster management and humanitarian relief situations. Based on findings three example laboratories were theoretically designed; structural modelling, systems simulation and optimization and sensitivity analyses were performed with HOMER Pro, PackVol and SketchUp. A cost benefit analysis was performed with the social return on investment methodology. Novel human waste processing was performed with fly ash and simulated faeces. Bacterial species identification in ice samples was performed with the API 20E protocol and limited equipment as a proof of concept for field deployment. A hybrid system consisting of PV panels, a wind turbine and biomass generator showed promise for displaced humanitarian relief camps; with every 1 ZAR capital invested resulting in 3.13 ZAR social benefit. A system consisting of PV panels and a battery bank proved to have the least environmental impact and the grid supply laboratory showed a cheaper cost of energy alternative for needs provision. Fly ash showed potential as in nutrient recovery and as a fertility aid to soil. The units developed function as a means to increase disaster preparedness and humanitarian relief as well a means to improve quality of life for rural marginalize populations.
- Full Text:
- Date Issued: 2017
- Authors: Nicholson, Thomas J
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/65167 , vital:28700
- Description: Intermittent energy and water supply are current challenges faced by many residents in South Africa. South Africa is one of the more water scarce countries in the world; this coupled with the lack of infrastructure makes it challenging to provide every citizen with their right to basic water and sanitation. With millennium development goal 7C not being addressed in many areas, residents experience sub-standard living conditions, which drastically increases the vulnerability of marginalised groups to epidemics. In the sustainable development goals improving sanitation and drinking water has been identified as one of the most effective and least expensive means of reducing fatalities and increasing public health. There is a need for a mobile laboratory that demonstrates power and water self-sufficiency, which is capable of on-site diagnosis and water treatment. The unit will have the ability to perform independent compliance monitoring of municipal water supply, treat inadequate water and provide surplus electricity to surrounding areas. A literature-based study was performed utilizing several scientific databases to identify current methods of power and water production in previous disaster management and humanitarian relief situations. Based on findings three example laboratories were theoretically designed; structural modelling, systems simulation and optimization and sensitivity analyses were performed with HOMER Pro, PackVol and SketchUp. A cost benefit analysis was performed with the social return on investment methodology. Novel human waste processing was performed with fly ash and simulated faeces. Bacterial species identification in ice samples was performed with the API 20E protocol and limited equipment as a proof of concept for field deployment. A hybrid system consisting of PV panels, a wind turbine and biomass generator showed promise for displaced humanitarian relief camps; with every 1 ZAR capital invested resulting in 3.13 ZAR social benefit. A system consisting of PV panels and a battery bank proved to have the least environmental impact and the grid supply laboratory showed a cheaper cost of energy alternative for needs provision. Fly ash showed potential as in nutrient recovery and as a fertility aid to soil. The units developed function as a means to increase disaster preparedness and humanitarian relief as well a means to improve quality of life for rural marginalize populations.
- Full Text:
- Date Issued: 2017
An investigation into the feasibility of incorporating ketoconazole into solid lipid microparticles
- Authors: Jhundoo, Henusha Devi
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54701 , vital:26601
- Description: One of the major challenges of the oral administration of ketoconazole (KTZ), an inhibitor of sterol 14α demethylase, used in the management of systemic and topical mycoses in immuno-compromised and paediatric patients is the lack of availability of liquid dosage forms. In order to overcome this challenge, extemporaneous preparations have been manufactured by care-givers and health care providers by crushing or breaking solid oral dosage forms of KTZ and mixing with a vehicle to produce a liquid dosage form that can be swallowed by patients. However, the use of extemporaneous preparations may lead to under or over-dosing if the care-givers are not guided accordingly. Furthermore, the dearth of information on the stability of these KTZ-containing extemporaneous preparations may lead to ineffective antifungal therapy and complicate the problems of resistance as it is difficult to estimate the shelf-lives of these extemporaneous products under varying storage conditions due to the susceptibility of KTZ to chemical degradation. Therefore, there is a need for formulation scientists to develop novel drug delivery systems that avoid the need for extemporaneous preparations, possess well-established limits of stability and minimize the risks of systemic adverse effects to facilitate KTZ therapy. The use of solid lipid microparticles (SLM) as potential carriers for the oral administration of KTZ was investigated since solid lipid carriers are known to exhibit the advantages of traditional colloidal carriers. The research undertaken in these studies aimed to investigate the feasibility of developing and manufacturing solid lipid microparticles (SLM), using a simple micro-emulsion technique, as a carrier for KTZ. Prior to pre-formulation, formulation development and optimization studies of KTZ-loaded SLM, it was necessary to develop and validate an analytical method for the in vitro quantitation and characterization of KTZ in aqueous dispersions of SLM during development and assessment studies. An accurate, precise, specific and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method coupled with UV detection at 206 nm was developed, optimized and validated for the analysis of KTZ in formulations. Formulation development studies were preceded by solubility studies of KTZ in different lipids. Labrafil® M2130 CS was found to exhibit the best solubilising potential for KTZ. Pre-formulation studies were also designed to determine the polymorphic behavior and the crystallinity of KTZ and Labrafil® M2130 CS that was used for subsequent manufacture of the solid lipid carriers. DSC and FTIR studies revealed that there were no changes in the crystallinity of KTZ or Labrafil® M2130 CS following exposure to a temperature of 60°C for 1 hour. In addition the potential for physicochemical interaction of KTZ with the lipid Labrafil® M2130 CS was investigated using DSC and FTIR and the results revealed that KTZ was molecularly dispersed in Labrafil® M2130 CS and that it is unlikely that KTZ would interact with the lipid. It was therefore established that KTZ and Labrafil® M2130 CS were thermo-stable at a temperature of 60°C and thus a micro-emulsion technique could be used to manufacture the KTZ-loaded SLM. Drug-free and KTZ-loaded SLM were prepared using a modified micro-emulsion technique that required the use of an Ultra-Turrax® homogenizer set at 24 000 rpm for 5 minutes followed by the use of the Erweka GmbH homogenizer. SLM were characterized in terms of particle size (PS), zeta potential (ZP), shape and surface morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition drug loading capacity (DLC) and encapsulation efficiency (EE) of SLM for KTZ were assessed using RP-HPLC. Formulation development and optimization studies of KTZ-loaded SLM were initially aimed at selecting an emulsifying system that was able to stabilize the SLM in an aqueous dispersion. Successful formulations were selected based on their ability to remain physically stable on the day of manufacture. Pluronic® F68 used in combination with Lutrol® E40, Soluphor® P, Soluplus® produced unstable dispersions on the day of manufacture and these combinations were not investigated further. However, the formulation of a stable KTZ-loaded SLM dispersion was accomplished by use of a combination of Pluronic® F68, Tween 80 and sodium cholate as the surfactant system. Increasing amounts of Labrafil® M2130 CS resulted in the production of particles with low DLC and EE, a large PS and a relatively unchanged ZP. An optimum concentration of 10% w/v Labrafil® M2130 CS was selected to manufacture the KTZ-loaded SLM. Studies to determine the influence of KTZ loading on the quality of SLM revealed that concentrations of KTZ > 5% w/v led to a reduction in DLC and EE and an increase in PS with minimal impact on the ZP. Stability studies conducted at 25°C/65% RH and 40°C/75% RH for up to 30 days following manufacture revealed that batch SLM 15 manufactured using 10% w/v Labrafil® M2130 CS, 5% w/v KTZ and a combination of 4% w/v Pluronic® F-68, 2% w/v Tween 80 and 1% w/v sodium cholate produced the most stable dosage form when stored at 25°C/65% RH for up to 30 days. However, storage at 40°C/75% RH resulted in instability of the formulation. An aqueous dispersion of KTZ-loaded SLM has been developed and assessed and may offer an alternative to extemporaneous preparations used for KTZ therapy in paediatric and immuno-compromised patients.
- Full Text:
- Date Issued: 2015
- Authors: Jhundoo, Henusha Devi
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54701 , vital:26601
- Description: One of the major challenges of the oral administration of ketoconazole (KTZ), an inhibitor of sterol 14α demethylase, used in the management of systemic and topical mycoses in immuno-compromised and paediatric patients is the lack of availability of liquid dosage forms. In order to overcome this challenge, extemporaneous preparations have been manufactured by care-givers and health care providers by crushing or breaking solid oral dosage forms of KTZ and mixing with a vehicle to produce a liquid dosage form that can be swallowed by patients. However, the use of extemporaneous preparations may lead to under or over-dosing if the care-givers are not guided accordingly. Furthermore, the dearth of information on the stability of these KTZ-containing extemporaneous preparations may lead to ineffective antifungal therapy and complicate the problems of resistance as it is difficult to estimate the shelf-lives of these extemporaneous products under varying storage conditions due to the susceptibility of KTZ to chemical degradation. Therefore, there is a need for formulation scientists to develop novel drug delivery systems that avoid the need for extemporaneous preparations, possess well-established limits of stability and minimize the risks of systemic adverse effects to facilitate KTZ therapy. The use of solid lipid microparticles (SLM) as potential carriers for the oral administration of KTZ was investigated since solid lipid carriers are known to exhibit the advantages of traditional colloidal carriers. The research undertaken in these studies aimed to investigate the feasibility of developing and manufacturing solid lipid microparticles (SLM), using a simple micro-emulsion technique, as a carrier for KTZ. Prior to pre-formulation, formulation development and optimization studies of KTZ-loaded SLM, it was necessary to develop and validate an analytical method for the in vitro quantitation and characterization of KTZ in aqueous dispersions of SLM during development and assessment studies. An accurate, precise, specific and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method coupled with UV detection at 206 nm was developed, optimized and validated for the analysis of KTZ in formulations. Formulation development studies were preceded by solubility studies of KTZ in different lipids. Labrafil® M2130 CS was found to exhibit the best solubilising potential for KTZ. Pre-formulation studies were also designed to determine the polymorphic behavior and the crystallinity of KTZ and Labrafil® M2130 CS that was used for subsequent manufacture of the solid lipid carriers. DSC and FTIR studies revealed that there were no changes in the crystallinity of KTZ or Labrafil® M2130 CS following exposure to a temperature of 60°C for 1 hour. In addition the potential for physicochemical interaction of KTZ with the lipid Labrafil® M2130 CS was investigated using DSC and FTIR and the results revealed that KTZ was molecularly dispersed in Labrafil® M2130 CS and that it is unlikely that KTZ would interact with the lipid. It was therefore established that KTZ and Labrafil® M2130 CS were thermo-stable at a temperature of 60°C and thus a micro-emulsion technique could be used to manufacture the KTZ-loaded SLM. Drug-free and KTZ-loaded SLM were prepared using a modified micro-emulsion technique that required the use of an Ultra-Turrax® homogenizer set at 24 000 rpm for 5 minutes followed by the use of the Erweka GmbH homogenizer. SLM were characterized in terms of particle size (PS), zeta potential (ZP), shape and surface morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition drug loading capacity (DLC) and encapsulation efficiency (EE) of SLM for KTZ were assessed using RP-HPLC. Formulation development and optimization studies of KTZ-loaded SLM were initially aimed at selecting an emulsifying system that was able to stabilize the SLM in an aqueous dispersion. Successful formulations were selected based on their ability to remain physically stable on the day of manufacture. Pluronic® F68 used in combination with Lutrol® E40, Soluphor® P, Soluplus® produced unstable dispersions on the day of manufacture and these combinations were not investigated further. However, the formulation of a stable KTZ-loaded SLM dispersion was accomplished by use of a combination of Pluronic® F68, Tween 80 and sodium cholate as the surfactant system. Increasing amounts of Labrafil® M2130 CS resulted in the production of particles with low DLC and EE, a large PS and a relatively unchanged ZP. An optimum concentration of 10% w/v Labrafil® M2130 CS was selected to manufacture the KTZ-loaded SLM. Studies to determine the influence of KTZ loading on the quality of SLM revealed that concentrations of KTZ > 5% w/v led to a reduction in DLC and EE and an increase in PS with minimal impact on the ZP. Stability studies conducted at 25°C/65% RH and 40°C/75% RH for up to 30 days following manufacture revealed that batch SLM 15 manufactured using 10% w/v Labrafil® M2130 CS, 5% w/v KTZ and a combination of 4% w/v Pluronic® F-68, 2% w/v Tween 80 and 1% w/v sodium cholate produced the most stable dosage form when stored at 25°C/65% RH for up to 30 days. However, storage at 40°C/75% RH resulted in instability of the formulation. An aqueous dispersion of KTZ-loaded SLM has been developed and assessed and may offer an alternative to extemporaneous preparations used for KTZ therapy in paediatric and immuno-compromised patients.
- Full Text:
- Date Issued: 2015
Antimicrobial resistance awareness program at Settlers Hospital
- Manhanzva, Rufaro Immaculate
- Authors: Manhanzva, Rufaro Immaculate
- Date: 2019
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/97712 , vital:31475
- Description: Expected release date-April 2021
- Full Text: false
- Date Issued: 2019
- Authors: Manhanzva, Rufaro Immaculate
- Date: 2019
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/97712 , vital:31475
- Description: Expected release date-April 2021
- Full Text: false
- Date Issued: 2019
Application of quality by design to the manufacture of a multiparticulate prednisone dosage form
- Authors: Manda, Arthur
- Date: 2020-04
- Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
- Language: English
- Type: text , Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/117986 , vital:34583
- Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
- Full Text:
- Date Issued: 2020-04
- Authors: Manda, Arthur
- Date: 2020-04
- Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
- Language: English
- Type: text , Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/117986 , vital:34583
- Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
- Full Text:
- Date Issued: 2020-04
Assessment of pharmaceutical equivalence of topical cream products containing hydrocortisone acetate using in vitro release testing (IVRT)
- Mudyahoto, Nyengeterai Amanda
- Authors: Mudyahoto, Nyengeterai Amanda
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63384 , vital:28404
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
- Authors: Mudyahoto, Nyengeterai Amanda
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63384 , vital:28404
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
Bioethical analysis of selected biomedical issues in South Africa and other countries
- Authors: Rusere, Jean
- Date: 2021-04
- Subjects: To be added
- Language: English
- Type: thesis , text , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/178530 , vital:42948
- Description: Access restricted until April 2023. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-04
- Authors: Rusere, Jean
- Date: 2021-04
- Subjects: To be added
- Language: English
- Type: thesis , text , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/178530 , vital:42948
- Description: Access restricted until April 2023. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-04
Collaborative health literacy development: a World Health Organization workplace health promotion approach to address tobacco use
- Authors: Duxbury, Theodore Orlando
- Date: 2019
- Subjects: Tobacco use -- Health aspects , Smoking -- Health aspects , Employee health promotion , Employee health promotion -- Computer programs , Rhodes University -- Employees -- Tobacco use
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/104116 , vital:29930
- Description: Background: Non-Communicable Diseases (NCDs) are a major global public health threat and tobacco use in particular is the leading cause of preventable illness and mortality globally. Furthermore, vulnerable and socially disadvantaged people get sicker and die sooner, especially because they are at higher risk of being exposed to harmful products such as tobacco and have limited access to health services. Tobacco use also has a major impact on the workplace, adversely affecting work productivity and increasing absenteeism. Both the living and work environments, therefore, play an important role in contributing towards the NCD epidemic. Demographics, culture, behaviour change reluctance and health literacy are all factors which exacerbate tobacco prevalence in South Africa. Workplace health promotion, however, is not well established in many workplaces. This study aimed to develop, implement and evaluate the effectiveness of a culturallysensitive and contextually-appropriate collaborative workplace health promotion literacy programme on tobacco use, utilizing tailored health information leaflets and the Rhodes University peer educators support staff, guided by the World Health Organization Workplace Health Promotion Framework. Method: The research was conducted using a participatory action research approach, which involved four phases: Firstly, the Exploratory phase assessed tobacco-related health promotion policies and practices at Rhodes University; and established facilitating and constraining factors related to tobacco use. Secondly, the Educational health promotion phase involved designing and testing a health promotion educational intervention to address tobacco use related challenges, which took the form of culturally sensitive and appropriate health information leaflets to be used as an educational intervention Thirdly, in the Implementation phase health promotion training workshops were conducted with volunteering Rhodes University Peer Educators. Finally, an Evaluation phase involved evaluating the tobacco health promotion programme presented to the Rhodes University Peer Educators through a focus group discussion; and evaluating Peer Educator recall on the tobacco related health information discussed during the training workshops through a post-post intervention questionnaire. Eight semi-structured interviews (SSIs) and seven focus group discussions (FGDs) were conducted with support staff, peer educators and key stakeholders to establish the need for a comprehensive workplace health promotion initiative, and to identify the facilitating and constraining factors to conducting such an initiative on tobacco use at the University. Three health information leaflets (HILs) were developed collaboratively with the Peer Educators following a series of scientific, end-user testing approaches. The HILs were tested for readability, comprehension, actionability and suitability. A four-day health promotion training programme was conducted to improve user friendliness, memory retention and recall of the HILs by the peer educators and to improve tobacco related health literacy aspects. The participants’ memory recall was evaluated using a pre- and post-, and post-post-intervention questionnaire to evaluate knowledge transfer. The study participants were also equipped with the completed HILs to distribute to their peers and to use as reference sources of information when needed in future. Results: The peer educators and institutional management supported the need for a tobacco workplace health promotion intervention. The intervention and evaluation phase of this study proved that health information material developed was readable, actionable, suitable, userfriendly, culturally sensitive and contextually appropriate. The workshops resulted in a significant increase in the participants’ tobacco related health knowledge. Through the adoption of a collaborative approach to the research, the participants felt empowered and ready to be agents of change amongst their peers in the workplace. Recommendations: The collective use of external expert reviewers, end-user testing techniques and validated computer programmes are recommended to improve the validity of health promotion research outcomes. A longitudinal study that focus on behaviour change, specifically, with health evaluation and monitoring aspects could be conducted as the next step to this study.
- Full Text:
- Date Issued: 2019
- Authors: Duxbury, Theodore Orlando
- Date: 2019
- Subjects: Tobacco use -- Health aspects , Smoking -- Health aspects , Employee health promotion , Employee health promotion -- Computer programs , Rhodes University -- Employees -- Tobacco use
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/104116 , vital:29930
- Description: Background: Non-Communicable Diseases (NCDs) are a major global public health threat and tobacco use in particular is the leading cause of preventable illness and mortality globally. Furthermore, vulnerable and socially disadvantaged people get sicker and die sooner, especially because they are at higher risk of being exposed to harmful products such as tobacco and have limited access to health services. Tobacco use also has a major impact on the workplace, adversely affecting work productivity and increasing absenteeism. Both the living and work environments, therefore, play an important role in contributing towards the NCD epidemic. Demographics, culture, behaviour change reluctance and health literacy are all factors which exacerbate tobacco prevalence in South Africa. Workplace health promotion, however, is not well established in many workplaces. This study aimed to develop, implement and evaluate the effectiveness of a culturallysensitive and contextually-appropriate collaborative workplace health promotion literacy programme on tobacco use, utilizing tailored health information leaflets and the Rhodes University peer educators support staff, guided by the World Health Organization Workplace Health Promotion Framework. Method: The research was conducted using a participatory action research approach, which involved four phases: Firstly, the Exploratory phase assessed tobacco-related health promotion policies and practices at Rhodes University; and established facilitating and constraining factors related to tobacco use. Secondly, the Educational health promotion phase involved designing and testing a health promotion educational intervention to address tobacco use related challenges, which took the form of culturally sensitive and appropriate health information leaflets to be used as an educational intervention Thirdly, in the Implementation phase health promotion training workshops were conducted with volunteering Rhodes University Peer Educators. Finally, an Evaluation phase involved evaluating the tobacco health promotion programme presented to the Rhodes University Peer Educators through a focus group discussion; and evaluating Peer Educator recall on the tobacco related health information discussed during the training workshops through a post-post intervention questionnaire. Eight semi-structured interviews (SSIs) and seven focus group discussions (FGDs) were conducted with support staff, peer educators and key stakeholders to establish the need for a comprehensive workplace health promotion initiative, and to identify the facilitating and constraining factors to conducting such an initiative on tobacco use at the University. Three health information leaflets (HILs) were developed collaboratively with the Peer Educators following a series of scientific, end-user testing approaches. The HILs were tested for readability, comprehension, actionability and suitability. A four-day health promotion training programme was conducted to improve user friendliness, memory retention and recall of the HILs by the peer educators and to improve tobacco related health literacy aspects. The participants’ memory recall was evaluated using a pre- and post-, and post-post-intervention questionnaire to evaluate knowledge transfer. The study participants were also equipped with the completed HILs to distribute to their peers and to use as reference sources of information when needed in future. Results: The peer educators and institutional management supported the need for a tobacco workplace health promotion intervention. The intervention and evaluation phase of this study proved that health information material developed was readable, actionable, suitable, userfriendly, culturally sensitive and contextually appropriate. The workshops resulted in a significant increase in the participants’ tobacco related health knowledge. Through the adoption of a collaborative approach to the research, the participants felt empowered and ready to be agents of change amongst their peers in the workplace. Recommendations: The collective use of external expert reviewers, end-user testing techniques and validated computer programmes are recommended to improve the validity of health promotion research outcomes. A longitudinal study that focus on behaviour change, specifically, with health evaluation and monitoring aspects could be conducted as the next step to this study.
- Full Text:
- Date Issued: 2019
Comparison of a novel HPLC method and conventional protein assays for the quantitation of insulin aspart in Novorapid®
- Authors: Dickson, Courtney Rae
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290704 , vital:56776
- Description: Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Dickson, Courtney Rae
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290704 , vital:56776
- Description: Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
- Full Text:
- Date Issued: 2022-04-06
Composition and fate of triclosan in the sludge from wastewater treatment in Grahamstown, South Africa and Tiaret, Algeria
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Development and assessment of 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
Development and assessment of gastric-retentive sustained release metronidazole microcapsules
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Development and assessment of gastroretentive sustained release captopril micro-balloons
- Authors: Oridota, Omoyosola Omolola
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63491 , vital:28419
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
- Authors: Oridota, Omoyosola Omolola
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63491 , vital:28419
- Description: Expected release date-April 2020
- Full Text:
- Date Issued: 2018
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