Doctor Pharmaceuticae - DPharm

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A Reductionistic Epistemology utilizing Brain Laterality which Investigates Pharmacists' Ideal Interactive Environment
(University of the Western Cape, 2018) Symon, Bernard Dennis; Butler, Nadine
The brain laterality of pharmacists may influence where the pharmacists are best suited to work. Brain laterality refers to the asymmetry of the hemispheres of the brain with regard to specific cognitive functions, such as objectivity and emotion. The left hemisphere functions objectively and rationally, whereas the right hemisphere is subjective and non-rational. Animal behaviour in the literature demonstrated an influence of brain laterality, thus selecting an ideal work environment may also be driven by brain laterality bias. Further support for the research included: amblyopia; hemiplegia; the WADA test. The research question investigated the matching of the brain laterality groups of pharmacists to their ideal work environments. The aims investigated: ear, eye, hand and foot dominance in determining brain laterality; influence of brain laterality and reductionistic variables on job choice; location of emotion generation and job choice. Five objectives investigated these aims: influence of brain laterality alone; influence of brain laterality and reductionistic variables; influence of a new brain laterality determining continuum; Propinquity Principle in achieving data; correctness of the Right Hemisphere Theory (RHT) or the Valence Theory (VT). The RHT suggests that the right hemisphere is dominant in processing all emotion. The VT argues that the left hemisphere is specialised in processing the positive emotions while the right hemisphere is specialised in processing the negative emotions. The resulting Null Hypothesis posits that there is no statistical difference between the different brain laterality groups enabling pharmacists to work competently in any placement. The Alternative Hypothesis was that there is a statistical difference between the brain laterality groups, thus brain laterality can be used to best place pharmacists into ideal placements.
Adverse pregnancy outcomes among HIV-positive pregnant women treated with efavirenz-containing antiretroviral drugs: a retrospective cohort study in the Cape Flats
(University of the Western Cape, 2017) Mohammednur, Mohammedmekin Mohammedseid; Mugabo, Pierre
The use of efavirenz (EFV) in the first trimester of pregnancy remains controversial. In South Africa, the use of EFV-containing antiretroviral therapy (ART) as part of a Fixed Dose Combination (FDC) during the first trimester of pregnancy started in April, 2013. Literature to date has reported conflicting outcomes following the use of EFV-containing ART during the first trimester of pregnancy. The objectives of the study were to determine the prevalence of adverse pregnancy outcomes among HIV-positive pregnant women treated with EFV-containing ART and compare these results with those of pregnant women treated with NVP-containing ART and HIV-negative pregnant women in resource-limited settings. In addition, the study also aimed to determine the effect of the time of initiation of ART on the prevalence of adverse pregnancy outcomes.
Aspects of the gastrointestinal uptake and metabolism of luteolin derivatives from Artemisia afra aqueous extract (preclinical)
(University of the Western Cape, 2011) Mukinda, James Tshikosa; School of Pharmacy; Faculty of Community and Health Sciences
The aim of this study was to investigate the effect the plant matrix and the structure of the flavonoid (i.e. whether aglycone or glycoside) may have on the gastrointestinal uptake and metabolism of luteolin derivatives from Artemisia afra traditional plant medicine. Specifically, how these two factors influenced the intestinal uptake and disposition of luteolin derivatives in pure and in Artemisia afra plant extract forms were to be assessed by investigating the uptake and metabolism of the luteolin derivatives in human intestinal epithelial Caco-2 cells and the perfused rat intestinal loop. To realize this aim, the following were determined: (1) identification and characterization of major luteolin derivatives found in Artemisia afra, (2) the effect of the plant matrix on the uptake of luteolin derivatives in Artemisia afra aqueous-extract forms across the Caco-2 cell monolayer, (3) the effect of the plant matrix on the absorption and metabolism of luteolin derivatives in Artemisia afra aqueous-extract forms in the perfused rat small intestine, (4) the effect of gut contents on the uptake and metabolism of luteolin derivatives in intestinal loop and (5) the metabolic profiles of luteolin derivatives obtained for the pure solutions versus plant aqueous extract solutions in Caco-2 cells and the rat intestine.
Cardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive rats
(2009) Chibuzo, Obikeze Kenechukwu; Mugabo, Pierre; Green, Ivan
Plants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg – 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kg– 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg – 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects.
Content levels, in vitro dissolution and predicted bioavailability of flavonoids from Sutherlandia frutescens leaf powder and aqueous extracts
(University of the Western Cape, 2015) Mbamalu, Oluchi Nneka; Syce, James; Samsodien, Halima
Various formulations of the popular South African medicinal plant, Sutherlandia frutescens,are commercially available, with no documented specifications for quality assessment. With plans already underway for a clinical trial to assess its efficacy in HIV patients, there is a need for scientifically validated tests for the quality control of products of this plant. Chemical constituents of the plant are many and varied but it is still unclear which might be the most appropriate ones to monitor for activity or to describe the quality of the plant’s products. For quality control and regulatory purposes, the content and dissolution of flavonoids in the plant products can be assessed. However, these compounds are not monitored for regulation and there are as yet no HPLC or dissolution methods that can be employed for quality control of herbals like S. frutescens. Therefore, the objectives of this study were to assess the suitability of its flavonoid constituents as quality control (QC) marker compounds, and the suitability of content levels and dissolution tests of flavonoids as QC tools for S. frutescens products. To realise the afore-mentioned objectives, non-commercially available flavonoid compounds (sutherlandins) that could be used as marker compounds were isolated from S. frutescens. An HPLC assay was developed and validated for determination of flavonoid content in solution. Five S. frutescens materials viz leaf powder (LP), spray-dried aqueous extract (SDAE) and freeze-dried aqueous extracts (FDAE) were analysed for flavonoid content and dissolution. Dissolution tests were conducted for different S. frutescens materials and dissolution profiles of flavonoids in capsules containing these materials were compared using Q-release values, the similarity factor (f2) and mathematical models. To predict in vivo bioavailability of the flavonoids, in silico assessment of in vivo bioavailability of flavonoids (glycosides and aglycones) that may be contained in different S. frutescens materials was conducted. Sutherlandins A, B, C and D were successfully isolated (percentage purity approximately99 % for sutherlandins A, C and D, and 90 % for sutherlandin B) and identified, and used, along with other flavonoid compounds, for the development of a simple and robust HPLC method. Content of sutherlandins A, B, C and D, quercetin and kaempferol in different plant materials were 0.4 ± 0.3, 0.8 ± 0.2, 1.3 ± 0.2, 0.6 ± 0.1, 0.01 ± 0.02 and 0.08 ±0.1 %,respectively, and differed significantly (p < 0.001). In vitro dissolution showed faster dissolution of flavoniod glycosides compared to aglycones. The flavonoids from the LP and SDAE materials showed characteristics of immediate release with Q75 in ≤ 45 minutes, and delayed release from the FDAE material, i.e. Q75 > 45 minutes. The dissolution profiles of each flavonoid compared from different S. frutescens materials were different as signified by their f2 values which were all below 50. The mathematical models describing release were also different for each flavonoid from the different S. frutescens materials. For in vivo bioavailability modelling and prediction studies, the flavonoid aglycones met the conditions for oral bioavailability while the flavonoid glycosides did not. In conclusion, the sutherlandins isolated from S. frutescens proved to be good markers for HPLC assay and dissolution tests of S. frutescens materials. The HPLC method was suitable for assessing flavonoid levels in S. frutescens materials, and also showed differences in flavonoid content in these materials. The dissolution method was simple and reproducible, and Q-release values, the f2 and mathematical models proved to be good tools for differentiating between S. frutescens materials. In silico modelling showed that the flavonoid glycosides and aglycones differed in oral bioavailability. Although not presently required by the Medicines Control Council (MCC), quantification, release and dissolution studies and specifications may be employed as tools for routine analysis and for quality control of herbal drug formulations containing S. frutescens.
Design and synthesis of new scaffolds as antiproliferative agents and potential hsp90 inhibitors
(University of Western Cape, 2020) Adegoke, Yusuf Adeyemi; Beukes, Denzil R.
Natural products have been an important source of drugs and novel lead compounds in drug discovery. Their unique scaffolds have led to the synthesis of derivatives that continue to give rise to medicinally relevant agents. Thus, natural product-inspired drugs represent a significant proportion of drugs in the market and with several more in development. Cancer is among the leading public health problems and a prominent cause of death globally. Chemotherapy has been important in the management of this disease even though side effects that arise due to lack of selectivity is still an issue.
Development of rifampicin loaded in surface-modified 4.0 G PAMAM dendrimer as a novel antituberculosis pulmonary drug delivery system
(University of the Western Cape, 2020) Ahmed, Rami M. Y.; Samsodien, Halima
Introduction: Tuberculosis (TB) is a serious bacterial infections caused by the Mycobacterium Tuberculosis (MTB) organism affecting mainly the lungs. Occasionally, MTB bacilli may be transported out of the pulmonary region and infect peripheral organs causing extra-pulmonary tuberculosis. Many therapeutic agents were developed over the years to combat TB, however the rapid emergence of resistant strains hampered their use. Furthermore, most of the current anti-TB drugs experience many challenges, which can be summarized in treatment regimen factors, drug-drug interactions, and physicochemical characteristics factors (such as hydrophobicity and low permeability into alveolar macrophages). These challenges have a significant role in treatment failure and the emergence of resistant TB. Due to the lack of newly discovered anti-TB drugs, and the absence of effective vaccines, many scientists have suggested the use of novel modalities for the current anti-TB drugs to enhance their efficacy and overcome some of the drawbacks. One of these modalities is nanotechnology-based drug delivery systems. Most of the anti-TB drugs experience low drug distribution to the lung and particularly alveolar macrophages within which the MTB resides, leading to treatment failure. Employing nanoparticles as drug delivery systems can have a significant impact on improving the pharmacokinetic profile of anti-TB drugs, the feasibility of different routes of administration, enhancing drug permeability, controlled/sustained drug release, and targeting specific disease sites. Collectively, these impacts will aid in enhancing drug concentration at the site of infection and reduce dosing and regimen duration. Dendrimers, such as polyamidoamine (PAMAM) dendrimers, are synthetic polymeric nanoparticles that have unique features that afford a dendrimer-conjugate complex the possibility to overcome the most common hurdles associated with drug delivery and treatment of diseases. Obstacles associated with solubility, permeability, inadequate biodistribution associated side effects may be enhanced. Manipulating the outermost surface functional groups with various ligands and polymers, will enhance the dendrimer properties and targeting potential. Aim: This study aims to develop a novel pulmonary delivery system for the anti-TB drug rifampicin using surface-modified G4 PAMAM dendrimer nanoparticles (polyethylene glycol (PEG) or mannose moieties), to improve drug solubility, prolong-release, enhance permeability into the macrophages, and decrease the toxicity of the drug-dendrimer conjugates. Methods: PAMAM dendrimers having increasing concentrations of poly(ethylene glycol) (PEG) 2 kDa or mannose residues were synthesized. The 4-nitrophenyl chloroformate was used as an activator in the case of PEG functionalization, while for the mannose conjugation the 4-isothiocyanatophenyl alpha-D-mannopyranoside (4-ICPMP) directly interacted with the primary amines of the dendrimer. The conjugated PEG polymers and mannose moieties on the dendrimer periphery were confirmed using FTIR and 1H NMR analytical techniques. Thereafter, rifampicin was loaded into the native and surface-modified dendrimers via a simple dissolution solvent evaporation method. Rifampicin-loaded dendrimers were then characterized using several analytical techniques namely; FTIR, DSC, NMR, SEM, and DLS. The polymer encapsulation efficiency (EE%) and percentage of drug loading (DL%) were determined directly using a validated HPLC method. In vitro drug release was studied at pH 7.4 and pH 4.5. The MTT technique was used to assess the cytotoxicity of the dendrimer formulations against raw 264.7 cell lines. Finally, the uptake of dendrimer nanoparticles by raw macrophages was studied using a flow cytometer and fluorescence microscopy techniques. Results: The percentage coverage of 4.0 G PAMAM dendrimer peripheral with PEG was achieved in a range of 38% - 100%, while for mannose moieties was from 44% - 100%. The EE% of unmodified dendrimer was 7.5% (w/w). The EE% of PEGylated dendrimers ranged from 65.0% - 78.75% (w/w), whereas for mannosylated dendrimers was from 43.43% - 57.91% (w/w). The size of the unloaded dendrimer nanoparticles was less than 25 nm, a gradual increase in the size after drug conjugation followed. The zeta potential of dendrimers was positive with values greater than 12 mV, the nanoparticle's zeta potential decreased upon increasing the density of PEG/mannose and after drug loading. FTIR and NMR data showed that rifampicin molecules were conjugated to the dendrimer at three sites; at the surface amines via electrostatic linkages, within the PEG/mannose, and into the dendrimer interior. SEM images of dendrimer nanoparticles confirmed the spherical shape of particles, and DSC data verified drug entrapment. Drug release was found to be affected by the pH of the medium and the extent of dendrimer functionalization. At the physiologic pH, surface-modified dendrimers showed a slower release rate compared to the unmodified dendrimer and free drug. Among surface-modified dendrimers, the release rate was inversely associated with the density of PEG/mannose molecules. At pH 4.5, a relatively higher drug release from all formulations was observed which suggests a burst release inside the alveolar macrophages. Toxicity studies showed that the unmodified dendrimer experienced time-dependent and concentration-dependent cytotoxicity against raw 264.7 cells. The toxicity gradually decreased upon increasing the density of PEG/mannose, and negligible toxicity was detected for formulations with 100% functionalization. Dendrimer nanoparticles were successfully internalized into raw cells after 24 hrs of incubation. The order of nanoparticles permeability was PEG 100% < PEG 85% < PEG 70% < PEG 49% < PEG 38% < unmodified dendrimer < mannose 44% < mannose 69% < mannose 93% < mannose 100%. The significant increase in the uptake of mannosylated dendrimers was due to the interaction with lectin receptors at the surface of raw macrophages, whereas the lower internalization of PEGylated dendrimers was due to the shielding of the surface positive charges. Conclusion: The in-vitro and ex-vivo data studies suggested that the developed novel surface-modified G4 PAMAM dendrimers are suitable drug carriers in terms of biocompatibility, release behaviour, and site-specific delivery of the anti-TB drug rifampicin.
The development, implementation and evaluation of an integrated framework for undergraduate pharmacy education in maternal and child health at the University of the Western Cape
(University of the Western Cape, 2022) Egieyeh, Elizabeth Oyebola; Bheekie, Angeni
The high rate of maternal and child mortality is a global health concern. Nationally, it is one of South Africa’s quadruple disease burdens. The Sustainable Development Goal 3, 2030 targets related to maternal and child health (MCH) were implemented to reduce the rate of mortality. The interventions that led to reducing mortality rates during the Millennium Development Goals era, such as improved access to quality healthcare services and skilled healthcare workers, need to be scaled up and accelerated to achieve the SDG 3 targets. As easily accessible frontline healthcare workers, pharmacists play an essential role in the continuum of care for MCH as guided by international and local regulatory health bodies. However, studies have shown that pharmacists feel ill-prepared and uncomfortable rendering MCH services, attributed to most pharmacy schools’ curriculum content and teaching methods.
Discovery of antibacterial lead compounds from marine organisms
(University of the Western Cape, 2020) Afolayan, Omolola; Beukes, Denzil R; Trindade, Marla
Marine organisms including algae and bacteria are known to produce chemically diverse secondary metabolites for survival purposes in the marine environment. Scientists have identified some of these natural products as therapeutic agents including some antibiotics. Given the increase in the resistance of pathogenic microorganisms especially methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis to commonly prescribed antibiotics, researchers have turned towards exploiting marine natural products for new antibacterial compounds. Due to the proven success of finding bioactive compounds in the marine environment this study therefore aims to discover lead compounds against MRSA and Mycobacterium tuberculosis from two marine sources, the marine algae and the bacteria associated with marine invertebrates referred to as bacterial isolates.
Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive wistar rats
(University of the Western Cape, 2011) Raji, Ismaila; Mugabo, Pierre; School of Pharmacy
Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 mg/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50 g/kg), losartan (30 mg/kg), phenylephrine (0.01 ; 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 ; 10.0mg/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 mg/kg), and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5; months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10 mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student t test for significant difference (p < 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p < 0.05) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p < 0.05) increased the BP, while propranolol, muscarine and atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent; with both increases as well as decreases observed with ang I, and II and atropine, while decreases were seen with muscarine. Captopril produced significant (p < 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p < 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin. The co-infusion of dobutamine with T. violacea produced siginificant (p < 0.05) increases in DBP which were associated with significant (p < 0.05) reductions in HR, when compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to dose dependent significant (p< 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or captropril produced (a) signicant (p < 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced signifiant (p< 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the beta; adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also suggest that the MLE may not act through the angiotensin II receptors or the alpha adrenergic receptors.
Effects of Leonotis leonurus aqueous extract on the isolated perfused rat heart
(University of the Western Cape, 2007) Khan, Fatima; Mugabo, P.; Burger, A. P.
An aqueous extract prepared from the leaves and smaller stems of Leonotis leonurus was used to investigate the potential effects on certain cardiovascular parameters, such as left ventricular systolic pressure, end-diastolic pressure, developed pressure, heart rate, cardiac work and coronary perfusion pressure in isolated rat hearts. Hearts were perfused at constant flow for 3min using the modified Langendorf! perfused model of the heart. Effects of adrenaline and digoxin solutions on the isolated heart were compared to that of the plant extract. Adrenaline produced both positive inotropic and chronotropic effects. Adrenaline increased (p
Evaluation of selected polycyclic compounds as resistance modulators in Mycobacterium tuberculosis
(University of the Western Cape, 2022) Kapp, Erika; Malan, Sarel
Progressive development of resistance to various chemotherapeutic agents used in the management of infectious diseases presents a serious problem in global public health. Increasing levels of antimicrobial resistance in Mycobacterium tuberculosis (Mtb) is particularly concerning in resource poor countries with a high incidence of tuberculosis (TB), as it is particularly difficult and very costly to treat. The Global Tuberculosis report released by the World health Organization (WHO) in 2022 (based on data from 2021) reports that South Africa is one of only 5 countries in the world with more than 500 cases per 100 000 people. It also falls in the WHO’s top 7 countries with the highest multidrug resistant (MDR) TB incidence.1 The same report released in 2021 states that global TB reporting rates dropped dramatically in 2020, and that TB death rates saw the first year-on-year increase since 2005.2 This is likely a direct consequence of COVID-19 and although improvements in reporting was seen in 2021, the trend has not yet been reversed.1 The pandemic had a negative impact on the progress made in the fight against TB and a renewed effort is needed to achieve the goals previously set out in the WHO End TB Strategy.
Expanding presumptive male partner management of sexually transmitted infections (STIs) to Western Cape, South African community retail pharmacies
(University of the Western Cape, 2007) Ward, Kim Lana; Butler, Nadine; Mugabo, Pierre; School of Pharmacy; Faculty of Science
The effect of industrialisation has thrust the pharmaceutical profession into a clinical paradigm where the approcah to pharmaceutical decisions is more disease and patient orientated. Consequently, South African community pharmacies are inundated with requests from the public for advice and treatment on a wide range of medical conditions, including sexually transmitted infections (STI's). Although community pharmacies are often the first port of call for undiagnosed STI, limited diagnostic skills and legally-imposed prescribing restrictions preclude pharmacists from providing the necessary clinical management. The overarching goal of this dissertation was to present objective arguments and evidences (new and existing) around an expanded role for pharmacists in STI partner management.
An exploratory study of the problem of training and skills development in the public health sector: The case of two district hospitals in the Limpopo province
(University of the Western Cape, 2022) Nefale, Mulalo; Esau, Michelle V.
Public health sectors across the globe are usually faced with challenges of adopting creative ways to improve performance and service delivery in the form of investing in employee skills development and training. During the apartheid era, employee training and skills development were reserved for the white minority group. The South African dawn of democracy in 1994 did not automatically result in a change in the status quo. In spite of various regulatory frameworks that emphasise skills development and training, skills development is still a problem, more than 25 years later. Amidst the high unemployment levels, there is also a short supply of critical skills or scarce skills in key sectors such as health.
Factors affecting the pharmacokinetics of vancomycin in children admitted to the intensive care unit (icu) of the Red Cross War Memorial Children's Hospital (RCWMCH).
(University of the Western Cape, 2023) Akunne, Onyinye Onyeka; Mugabo, Pierre
Vancomycin is a glycopeptide antibiotic that inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminal end of cell wall precursor units preventing the elongation and cross-linkage of the peptidoglycan. Vancomycin is used to treat infections with gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (S. aureus), coagulase-negative staphylococci and penicillin-resistant Streptococcus pneumoniae (S. pneumoniae). It is a time-dependent drug, and its efficacy depends on the duration of pathogen exposure to vancomycin. Low plasma concentration may lead to treatment failure and the re-emergence of bacterial resistance. Vancomycin is known to cause adverse effects at high concentrations. Therefore, it is necessary to monitor plasma concentrations to maintain vancomycin concentration within the therapeutic window. Vancomycin is mainly administered as an intravenous (IV) infusion as it is poorly absorbed from the gastrointestinal system.
The formulation and evaluation of indomethacin tablets
(University of the Western Cape, 1998) van Niekerk, Johan
The overall objective of this research is to attempt to produce, by direct compression, indomethacin tablets which have good dissolution characteristics and an improved bioavailability profile, when compared to the capsule formulations currently available. In order to use the direct compression method, the solubilized form of indomethacin should have good flow properties, as well as a small bulk volume for incorporation into reasonably sized tablets.
The formulation of a microsphere based fixed dose combination for oral antiretroviral delivery
(University of the Western Cape, 2023) Omoteso, Omobolanle Ayoyinka; Aucamp, Marique Elizabeth
The cost of providing antiretroviral therapy (ART) remains a significant economic burden on African countries due to poverty and a lack of resources. To reduce the economic burden of HIV infection, a formulation scientist must use the limited resources available in Africa to develop drug dosage forms of antiretrovirals (ARVs) that are cost-effective, adaptable, and accessible, as well as result in successful therapeutic outcomes of HIV/AIDS treatment, raise the average life expectancies of HIV-positive adults, and increase the availability of the limited resources for other purposes. According to the literature, lamivudine (3TC) is still used in firstline HIV treatment regimens, and several 3TC-based fixed-dose combinations (FDCs) are on the market. These FDCs are typically relatively large and require patients to take medication daily. As a result, patients will accept a flexible dosage form that can be ingested once and provides adequate therapeutic efficacy for more than 24 hours, thereby increasing treatment adherence, decreasing drug resistance, and improving therapeutic efficacy. Formulation scientists must create dosage forms that provide better patient treatment and patient experience, focusing on patientcentred medicine development. Hence, this study focused on 3TC and tenofovir disoproxil fumarate (TDF), which are still among the cornerstones of many HIV treatment regimens.
An investigation into the medicinal properties of Tulbaghia alliacea phytotherapy
(University of the Western Cape, 2009) Thamburan, Samantha; Johnson, Quinton
The reproductive health of individuals is severely compromised by HIV infection, with candidiasis being the most prevalent oral complication in patients. Although not usually associated with severe morbidity, oropharyngeal candidiasis can be clinically significant, as it can interfere with the administration of medications and adequate nutritional intake, and may spread to the esophagus. Azole antifungal agents are commonly prescribed for the treatment and prophylaxis of candidal infections. However, the emergence of drug resistant strains and dose limiting toxic effects have complicated the treatment of candidiasis. Consequently, safe and effective and affordable medicine is required to combat this fungus. Commercial garlic (Allium sativum) has been used time since immemorial as a natural antibiotic, however very little is known about the antifungal properties of two indigenous South African species of garlic, namely Tulbaghia alliacea and Tulbaghia violacea, that are used as folk medicines for a variety of infections. This study compares the in vitro anti-candidal activity of Tulbaghia alliacea, Tulbaghia violacea and Allium sativum extracts. It was found that the greatest concentrations of inhibitory components were extracted by chloroform or water. The IC50 concentrations of Tulbaghia alliacea were between 0.007 – 0.038% (w/v). Assays using S. cerevisiae revealed that the T. alliacea extract was fungicidal, with a killing half-life of approximately 2 hours. This inhibitory effect of the T. alliacea extracts was observed via TLC, and may be due to an active compound called Marasmicin, that was identified using NMR. This investigation confirms that extracts of T.alliacea exhibit anti-infective activity against candida species in vitro.
An investigation into the medicinal properties of Tulbaghia alliacea phytotherapy
(University of the Western Cape, 2009) Thamburan, Samantha; Johnson, Quinton; School of Pharmacy; Faculty of Science
The reproductive health of individuals is severely compromised by HIV infection, with candidiasis being the most prevalent oral complication in patients. Although not usually associated with severe morbidity, oropharyngeal candidiasis can be clinically significant, as it can interfere with the administration of medications and adequate nutritional intake, and may spread to the esophagus. Azole antifungal agents are commonly prescribed for the treatment and prophylaxis of candidal infections. However, the emergence of drug resistant strains and dose limiting toxic effects have complicated the treatment of candidiasis. Consequently, safe and effective and affordable medicine is required to combat this fungus. Commercial garlic (Allium sativum) has been used time since immemorial as a natural antibiotic, however very little is known about the antifungal properties of two indigenous South African species of garlic, namely Tulbaghia alliacea and Tulbaghia violacea, that are used as folk medicines for a variety of infections. This study compares the in vitro anti-candidal activity of Tulbaghia alliacea, Tulbaghia violacea and Allium sativum extracts. It was found that the greatest concentrations of inhibitory components were extracted by chloroform or water. The IC50 concentrations of Tulbaghia alliacea were between 0.007 - 0.038% (w/v). Assays using S. cerevisiae revealed that the T. alliacea extract was fungicidal, with a killing half-life of approximately 2 hours. This inhibitory effect of the T. alliacea extracts was observed via TLC, and may be due to an active compound called Marasmicin, that was identified using NMR. This investigation confirms that extracts of T.alliacea exhibit anti-infective activity against candida species in vitro.
Investigation of common deficiencies observed in scientific assessments and the implementation of a new robust review pathway, the risk-based assessment approach, by the South African Health Regulatory Authority, SAHPRA
(University of the Western Cape, 2022) Moeti, Lerato Petunia; Joubert, Jacques
The main objective of this study is to improve patient access to medicines. The research is two-fold, the first component promotes transparency between the South African Health Products Regulatory Authority (SAHPRA), pharmaceutical companies, manufacturers and clinical research organisations by investigating deficiencies in scientific assessments of medicines submitted for approval. The common deficiencies from the regional, Active Pharmaceutical Ingredient (API), Finished Pharmaceutical Product (FPP) and Bioequivalence study sections of dossiers submitted to SAHPRA were qualitatively and quantitatively investigated. The investigation was conducted retrospectively between 2011 to 2017 for non-sterile and sterile generic products finalised by the P&A pre-registration Unit. To strengthen the conclusions, up-to-date data was also collected between 2020-2021 to confirm the consistency of the findings.

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