5th University of the Western Cape School of Pharmacy Postgraduate

Research Symposium

9 September 2019

Sponsored by

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Welcome!

Dear honoured guests, staff members and students

It is our immense pleasure to welcome you to the 5th annual UWC School of Pharmacy Postgraduate Research Symposium. The symposium covers a vast spectrum of research from the various disciplines of pharmacy. The research topics are headed by different aspects of many South African disease burdens including tuberculosis, cancer and Alzheimer’s amongst others. The discovery natural product derived- drugs from indigenous terrestrial plant and marine sources as well as in silico prediction of activities of potential molecules are explored. There has also been great development in the study of nanoparticles and similar drug delivery systems and the pharmaceutics department does not fall short of contributing to this. Pharmacy practice puts a great deal of effort into investing in research that will ultimately provide the best pharmaceutical care to the community.

Postgraduate students spend enormous time conducting their research in order to collect data. Therefore, it is crucial they need this privilege to share their work and as well improve on it through suggestions, questions and comments during the presentation. At this junction, we would like to congratulate those who have bagged their doctorate and masters degree within the last one year and to welcome the new postgraduate students. Their names are included at the end of this booklet.

We would like to thank our supervisors and academic and support staff of the School of Pharmacy for their guidance provided to the post-graduates. The symposium is sponsored by Aspen Pharmacare and with great support from Mr. Rudy Maart and Ms. Benita Van Rooyen

We wish a great success to the presenters and a happy and informative symposium to everyone.

Kind regards

Post-graduate Symposium Committee: Nnamdi Okafor, Prudence Munyayi, Ngabo Musafili, Saajida Momath, Samson Oselusi, Nazanin Afrogheh

Academic advisors: Prof. Denzil R. Beukes and Prof. Admire Dube.

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Message from the Director

Dear Postgraduates, Colleagues and Friends

On behalf of the UWC School of Pharmacy, I would like to welcome you to the 5th Pharmacy Postgraduate Symposium. Once again, we look forward to stimulating scientific presentations and learning from each other through interdisciplinary interaction.

Our vision remains to be the Premier Provider of Pharmacy Education in Africa with a Global Footprint in the Pharmaceutical Sciences and our mission to produce graduates and pharmaceutical scientists equipped to respond to the pharmaceutical and healthcare needs of South Africa. A forum like this provides for the scientific interaction and exchange of ideas necessary to stimulate the globally recognized research important and relevant for the society in which we live.

Presentations like these from postgraduate studies originating and developed here at UWC are the cornerstone on which we build the future success of the School of Pharmacy and attain our leadership and global recognition in learning, research and innovation.

We look forward to your active participation.

Sarel Malan

Professor and Director, School of Pharmacy, UWC

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Contents

Message from the Director .............................................................................................................. 3

Programme ...................................................................................................................................... 5

Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents ...................................................... 7

Investigating the potential drug-herb interaction between Sutherlandia frutescens and antituberculosis drugs ...................................................................................................................... 8

Exploring a Participatory multi-stakeholder engagement approach to address chronic medicine use .................................................................................................................................................... 9

The impact of Niacin on PCSK9 levels in Vervet monkeys (Chlorocebus aethiops) ................... 10

Population pharmacokinetics of ethionamide and ethionamide sulfoxide in patients with multidrug-resistant tuberculosis .................................................................................................... 11

Synthesis and characterization of biomimetic nanoparticles for macrophage activation: a strategy towards intracellular Mtb eradication. ........................................................................................... 12

Formulation and characterisation of corticosteroid loaded ethosomes for topical delivery ......... 13

Bioassay Guided Isolation of Angiotensin-Converting Enzyme Inhibitory Compound from Hypericum perforatum .................................................................................................................. 14

South African natural products as a potential source of new anti-parasitic drugs ........................ 15

Selection, synthesis and evaluation of novel drug-like compounds from a library of virtual compounds designed from natural products with antiplasmodial activities ................................. 16

Rifampicin and Isoniazid minimum inhibitory concentrations in patients with drug-resistant tuberculosis .................................................................................................................................... 17

Non-compartmental analysis of Vancomycin Pharmacokinetics in Critically Ill Children .......... 18

Synthesis and characterization of Isoniazid loaded mesoporous calcium carbonate microparticles ....................................................................................................................................................... 19

Pulmonary delivery of anti-tuberculosis drug rifampicin loaded in surface-modified fourth generation PAMAM dendrimer as a novel drug delivery system ................................................. 20

Investigating the interaction between the Hsp90 inhibitor, novobiocin, and human serum albumin by STD NMR ................................................................................................................................ 21

In Silico ADMET profiling of Phytochemicals isolated from Leonotis Leonurus ....................... 22

Descriptive and retrospective evaluation of empiric carbapenem-sparing regimens versus carbapenem antibiotics use in non-intensive care adult patients at Khayelitsha District Hospital (KDH) ............................................................................................................................................ 23

List of completions 2018 and 2019 ............................................................................................... 24

List of new postgraduate students 2019 ........................................................................................ 26

Notes .............................................................................................................................................. 27

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Programme

5th ANNUAL POST GRADUATE SYMPOSIUM 9 SEPTEMBER 2019 VENUE: SCHOOL OF PUBLIC HEALTH ROOMS 1A AND 1B

OPENING SESSION

08.50 Welcome and Opening Address Prof. Davies-Coleman

SESSION 1 Chairs: Prudence Munyayi and Saajida Momath

09:00 Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

Luke Zondagh

09:15 Investigating the potential drug-herb interaction between Sutherlandia frutescens and anti-tuberculosis drugs

Mokone Mmola

09:30 Exploring a Participatory multi-stakeholder engagement approach to address chronic medicine use

Bonheur Nfurayase

09:45 The impact of Niacin on PCSK9 levels in Vervet monkeys (Chlorocebus aethiops)

Thobile Ngqaneka

10:00 Population pharmacokinetics of ethionamide and ethionamide sulfoxide in patients with multidrug-resistant tuberculosis

Fanya Boulou

10:15 Synthesis and characterization of biomimetic nanoparticles for macrophage activation: a strategy towards intracellular Mycobacterium tuberculosis eradication.

Ephraim Maphasa

10:30 – 11h00 Morning Tea SESSION 2 Chairs: Nnamdi Okafor, and Ngabo Musafili,

11:00 Formulation and characterisation of corticosteroid loaded ethosomes for topical delivery

Bjorn Martin

11:15 Bioassay guided isolation of Angiotensin-converting enzyme inhibitory compound from Hypericum Perforatum

Marilyn Umugiraneza

11:30 South African natural products as a potential source of new anti- Achmat Kemies

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parasitic drugs

11:45 Selection, synthesis and evaluation of novel drug-like compounds from a library of virtual compounds designed from natural products with anti-plasmodial activities

Rostanda Fankam

12:00 Rifampicin and isoniazid minimum inhibitory concentrations in patients with drug-resistant tuberculosis Osaretin Okonji

12:15 Non-compartmental analysis of vancomycin pharmacokinetics in critically ill children Onyinye Akunne

12h30 Synthesis and characterization of isoniazid loaded mesoporous calcium carbonate microparticles Joseph Mutenga

12:45-14h00 Photograph & Lunch SESSION 3 Chairs: Samson Oselusi and Ngabo Musafili

14:00 Pulmonary delivery of anti-tuberculosis drug rifampicin loaded in surface-modified fourth generation PAMAM dendrimer as a novel drug delivery system

Rami Ahmed

14:15 Investigating the interaction between the Hsp90 inhibitor, novobiocin, and human serum albumin by STD NMR Julian Sheldon

14:30 In Silico ADMET profiling of phytochemicals isolated from Leonotis leonurus Chioma Uduma

14:45

Descriptive and retrospective evaluation of empiric carbapenem-sparing regimens versus carbapenem antibiotics use in non-intensive care adult patients at Khayelitsha District Hospital (KDH)

Isaac Mugoya

15:00 Closing remarks Prof. Beukes END OF PROGRAMME

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Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents Luke S. Zondagh, Sarel F. Malan, Jacques Joubert

School of Pharmacy, University of the Western Cape, Robert Sobukwe Road, Bellville, 7535, Cape Town, South Africa

Introduction: Alzheimer’s disease (AD) is a major neurodegenerative disorder and causes a massive socio-economic burden on modern society. The symptoms of AD include cognitive impairment and memory loss, amongst others. The exact pathophysiology of AD is unknown, but there are many theories which include; the oxidative stress-, amyloid- and cholinergic theory to name a few. Currently, no treatments are able to halt, slow down or reverse the progression of the disease. This may be due to the multifactorial causes of the disease as current treatments only target one factor of the disease. Multitarget-directed ligand (MTDL) design strategies are increasingly used with the potential to target multiple factors of AD simultaneously. Previous MTDL studies in developing anti-AD agents has exhibited promising results. Method: Novel MTDLs were developed to combat multiple factors of AD. Edaravone, a synthetic free radical scavenger, is being used as treatment for acute cerebral infarction and ALS. A substituted N-benzylpyridinium moeity in previous research has been used in MTDLs design approaches and has showed great potential as a cholinesterase (ChE) inhibitor. These two compounds were used to develop novel edaravone-benzyl pyridinium hybrid compounds. The proposed compounds were synthesized, purified and structurally characterized. Antioxidant (DPPH+), BuChE and AChE (using Ellman’s method) evaluations were performed and the results were examined to determine inhibitory activities. Molecular docking studies were conducted using Molecular Operating Environment software to determine the binding affinity and potential interactions of the new MTDLs within the AChE- and BuChE enzyme active sites. In silico blood-brain barrier (BBB) permeability and other physicochemical parameters were calculated and used to provide information on the drugability of the synthesized compounds. Results: The hybrid compounds were successfully synthesized and the structures were confirmed using NMR, MS and IR. The compounds were able to inhibit the AChE and BuChE enzymes with IC50’s in the low M range. Molecular docking studies indicated that the compounds are accommodated within both sites

of the ChE enzymes and interacted with important amino acids within these sites, which explain the good inhibition observed. BBB permeability prediction and other tests showed that the compounds should reach the CNS and have a high degree of oral bioavailability. The compounds also exhibited strong antioxidant activities. Conclusion: The novel MTDLs exhibited promising results as potential anti-AD agents. In addition, the results observed in the AChE inhibition assay and AChE molecular modelling studies indicate that these compounds may also be able to block AChE-induced amyloid-beta (Aβ) formation. Therefore, further inhibition studies on Aβ-plaque formation are ongoing to elaborate on the ability of these compounds to act as MTDLs for the treatment of AD.

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Investigating the potential drug-herb interaction between Sutherlandia frutescens and antituberculosis drugs Mokone Mmola1, Toinette Labuschagné2, Nai-Jen Hsu2, Muazzam Jacobs2, William Folk1,3and Denzil R. Beukes1 1 School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa; 2 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town South Africa; 3 Biochemistry Department, University of Missouri, Columbia, Missouri USA

Background: Tuberculosis (TB) affects millions of people worldwide and it is estimated that about 1% of the South African population develop active tuberculosis each year. HIV positive patients have weak immune system and therefore take plant extracts, such as Sutherlandia frutescens, for its “immune boosting” activity. However, a recent phase 1 clinical trial in HIV positive adults has uncovered the possible interference between S. frutescens and isoniazid (used as prophylaxis) in HIV positive patients, leading to the development of active tuberculosis. The mechanism with which this occurs will be investigated in this project. Methodology: Marker compounds, sutherlandins and sutherlandiosides were isolated from S. frutescens and completely characterized by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). These compounds were subsequently used to standardize aqueous (SFAE) and ethanolic (SFEE) extracts. The SFAE and SFEE extracts were assessed for their activity in a mouse model of tuberculosis at the University of Cape Town. Results and discussion: Sutherlandins (A-D) and sutherlandiosides (A-D) isolated from methanolic extract were characterized by full 2D NMR spectrosocopy and their structures confirmed. These compounds were also detected in aqueous, ethanolic and methanolic extracts by HPLC-DAD and UPLC-MS. Preliminary studies acquired by UCT collaborators showed that S. frutescens aqueous extract did not have any effect on the growth of Mtb (in vitro or in vivo) but appear to affect the efficacy of INH in the treatment of tuberculosis (in vivo). Conclusion: Although S. frutescens possesses health promoting qualities, it can be detrimental when it is co-administered with INH. Based on the preliminary results obtained, S. frutescens does not directly interfere with the growth of M. tuberculosis but appear to inhibit the activity of INH.

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Exploring a Participatory multi-stakeholder engagement approach to address chronic medicine use Bonheur Parfaite Nfurayase1, Cornel Hart2, Angeni Bheekie1, Mea Van Huyssteen1 1 School of Pharmacy; 2 Division of Postgraduate Studies, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: bnfurayase@uwc.ac.za

Introduction: The rising prevalence of non-communicable diseases in South Africa is a concern, despite progressive interventions. The collective involvement of higher education institutions, non-governmental organizations, community health workers and community members, in a “whole society” participatory approach, remains under-explored. Participatory appraisal methods to engage stakeholders could be an approach to address Chronic Medicine Use (CMU) in an underserved Cape Town suburb. Methods: This participatory action research (PAR) study design, engages pharmacy students and faculty, a non-governmental organization, community health workers and community representatives as research partners. The research partners participated in closed focus group participatory sessions, and a collaborative participatory workshop, to identify and develop initiatives to address chronic medicine use issues. Results: Three participatory appraisal tools were used in this project: i) the journey of change; ii) map of exchange; and CMU-thought pool. The journey of change tool revealed the internal and external challenges faced by stakeholders. The value of collaboration and networking with other bodies for the purpose of collaboration ?? and co-creation of new solutions were expressed by non-community stakeholders. The community stakeholders expressed the need for organizations and institutions to be more visible and accessible in communities. The map of exchange tool revealed the broken relationships between: i) the community and higher education institutions and ii) between the community and Primary Health care facilities. The relationships; between: i) the community and the community health workers; and ii) between the university and non-governmental organization were described as positive. The tool also revealed issues of power, hierarchal attitudes and detachment from the realities that communities face across all stakeholders. The map of exchange tool was a useful tool in appraising “which relationships needed mending so as to make this whole partnership thing possible” by the NGO stakeholder. The CMU-thought tool revealed the main issues of CMU to be: “adherence”; “acceptance”;” lack of support systems”; ”stigma”; ”education and follow-up” as well as ”neglected social issues”. The collaborative stakeholder workshop attended by all stakeholders produced a vast range of practical and almost “dream-like solutions” that all stakeholders believed warranted further exploration and potential execution to address CMU issues identified in the community. Conclusions: The PAR study design results from the multi-stakeholder context contributed to the solidification of existing partnerships and feelings of empowerment and value amongst the stakeholders. Additionally, the collaborative partnership nature of this project allowed for the exploration of CMU in a manner that allowed holistic ways in which community members experience chronic diseases. Practical and inexpensive solutions were collaboratively identified by all stakeholders.

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The impact of Niacin on PCSK9 levels in Vervet monkeys (Chlorocebus aethiops) Thobile Ngqaneka1, 2, Zandisiwe E. Magwebu ¹, Kenechukwu Obikeze ² and Chesa G. Chauke¹.

¹School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa; ²Primate Unit and Delft Animal Centre (PUDAC), South African Medical Research Council,Tygerberg, 7505, South Africa.

E-mail address: 3880262@myuwc.ac.za

Introduction: Currently, statins are recognized as the primary therapy for cardiovascular related diseases. However, due to the reported adverse reactions in patients using statin, there is an increasing interest in developing more effective LDL-C-lowering drugs that might supplement statins. Niacin has been used in combination with other LDL-lowering drugs (statins and fenofibrates), however the effect of such combined therapies on PCSK9 was observed to slightly decrease LDL-C. Therefore, the purpose of this study is to determine the circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in captive-bred Vervet monkeys and its interaction with niacin administration. Methods: Sixteen Vervet monkeys were divided into two groups (control and experimental) of eight animals and each group was matched according to age and gender. The experimental group received 100 mg/kg/day of niacin mixed into a 30 g portion of the maintenance diet of pre-cooked maize meal, whereas the control received the maintenance diet throughout the treatment period of three months (Time point 0-4). This was followed by four weeks of the washout period (T5). Food intake was recorded daily and clinical observations were conducted throughout the study. During each sampling point from baseline to washout (T0-T5), blood samples were collected into SST, EDTA and PAXgene tubes for lipogram, genotyping and gene expression analysis, respectively. The lipogram analysis of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were analyzed by PathCare. Results: A statistical significant increase was only observed for HDL (p=< 0.05) from T1 to T4 in the treated group. However, there was a slight decrease in LDL, cholesterol and triglycerides levels during the treatment period with niacin (100 mg/kg/day). These lipogram levels returned to normal after the washout period. Since the genetic part of the study is still in progress, the next phase will be to further correlate the lipogram findings with gene expression and genotyping. Conclusion: In this study, niacin administration slightly reduced LDL, cholesterol, triglycerides levels and significantly increased HDLs levels in the treated group. Based on these lipogram findings, it is therefore anticipated that there would be a down-regulation of PCSK9 gene in treated group specifically due to the decrease in LDL levels. However, this can only be confirmed after the completion of gene expression, which is still on-going.

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Population pharmacokinetics of ethionamide and ethionamide sulfoxide in patients with multidrug-resistant tuberculosis Fanya Boulou and Pierre Mugabo

School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail address: 3520946@myuwc.ac.za

Introduction: Ethionamide is an antituberculosis drug currently used in the treatment of multidrug- resistant tuberculosis (MDR-TB). It was demonstrated that its pharmacological activity comes from its active metabolite ethionamide sulfoxide. Nevertheless, in-depth literature is inexistent on the pharmacokinetic profile of the latter compared to the former. This study which is the first study reporting on the pharmacokinetic parameters of ethionamide sulfoxide in patients with MDR-TB aimed at describing the population pharmacokinetics of ethionamide and its active metabolite and determining the effect of patients’ demographics thereof. Methods: This study involved 34 patients with MDR- TB admitted for an intensive phase treatment at Brewelskloof Hospital in the Western Cape. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 8 and 24 h post drug administration. Using a developed and fully validated HPLC-MS - MS method, ethionamide and ethionamide sulfoxide were simultaneously quantified in patients’ plasma. Population parameters were estimated using Monolix 2019R1, a nonlinear mixed effects modelling software. Results: A transit compartment model best described the absorption of ethionamide with the following estimated population parameters: 2.38h, 1.98 h-1, 124L and 576 L/h respectively for mean transit time, biotransformation constant rate, volume of distribution and clearance. Ethionamide sulfoxide volume of distribution and clearance were 29L and 11.6L/h respectively. There was no statistically significant correlation between ethionamide pharmacokinetics parameters and covariates, whereas, a negative correlation was observed between the BMI and the volume of distribution of ethionamide sulfoxide (P=0.050). Conclusions: This model successfully described the disposition of ethionamide and ethionamide sulfoxide in the body. Yet, deeper research is required regarding ethionamide sulfoxide PK/PD relationship.

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Synthesis and characterization of biomimetic nanoparticles for macrophage activation: a strategy towards intracellular Mtb eradication. Ephraim Maphasa1, Sarah D’Souza, Mervin Meyer 2 and Admire Dube1 1School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa; 2Department of Biotechnology, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 3138676@myuwc.ac.za

Introduction: Tuberculosis (TB) is a common and often fatal disease caused by an infection from various strains of Mycobacterium, the most common being Mycobacterium tuberculosis (Mtb). Mtb is primarily resident within macrophages and these cells are inactivated by Mtb in the latent and active form of TB. As cases of multi-drug resistant TB are growing at an alarming rate, there is urgent need to develop novel strategies to eradicate Mtb. Our group has recently reported conjugation of curdlan (an immunostimulant polysaccharide derived from fungus) onto poly (D, Llactide- co-glycolide) (PLGA), the conjugate was later used to synthesize nanoparticles (NPs) that could activate macrophages. We now aim to further understand the interaction of these NPs with macrophages and to characterize the capacity of the NPs to stimulate phagosome maturation, autophagy, apoptosis and other intracellular pathways and proteomic changes required for the eradication of bacterial infections. In this paper, we present the synthesis of the NPs and their detailed characterization within in vitro and biologically relevant media. Methods: PLGA NPs functionalized with up to 8% (w/w) curdlan were synthesized using the emulsion solvent evaporation method. The size, polydispersity index (PDI), and zeta potential (ZP) of the NPs, and the evolution of these properties in different solutions were assessed over time using dynamic light scattering techniques. High resolution transmission electron microscopy (HR-TEM) was used to determine particle shape, Nuclear magnetic resonance spectroscopy (NMR) and X-ray photoelectron spectroscopy (XPS) were used to quantify curdlan on the NPs. 1D SDS-PAGE gel electrophoresis and the Bradford assay were used to study the protein corona form corona forming in supplemented cell media. Cytotoxicity was evaluated in RAW264.4 macrophages. Results: PLGA NPs with 0, 2, 5 and 8% (w/w) curdlan were successfully synthesized. The NPs were found to have a spherical shape and an average size of approximately (~) 400 nm, PDI of ~ 0.3 and ZP below -20 mV (accept for the NP with 8%, which had ZP of ~ 10 mV). The NPs were also found to maintain their physicochemical properties in both distilled water (dH2O) and supplemented DMEM. The presence and percentage of curdlan on the NP was confirmed, no statistical difference between the opsonisation of the NPs was observed, and no cytotoxicity was observed on macrophages after preliminary MTT assay studies. Conclusions: Biomimetic PLGA NPs were successfully synthesized using the emulsion solvent evaporation method; various characterization techniques were used to confirm the presence of curdlan on the NPs and the stability of the NPs in dH2O and supplemented DMEM. The NPs were also found to be non-toxic against macrophages, and the particles will subsequently be applied in stimulating macrophages against Mtb infection.

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Formulation and characterisation of corticosteroid loaded ethosomes for topical delivery Bjorn Franklin Martin, Naushaad Ebrahim, Halima Samsodien

School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 2857949@myuwc.ac.za

Introduction: Currently, corticosteroids (e.g. hydrocortisone and betamethasone) are the most widely used class of anti-inflammatory drugs. For transdermal drug delivery (TDD), these drugs are often included in topical formulations to treat a variety of skin diseases. However, TDD is challenging because the epidermal skin layer, the stratum corneum (SC), inhibits the permeation of foreign materials. Ethosomes are novel nano-carrier systems used for the delivery of drugs through the skin. The aim of this study was to formulate ethosomes encapsulated with betamethasone valerate (BMV) and to characterise the prepared ethosomes using analytical techniques. Methods: Ethosomes were prepared using a modified version of the double emulsion (water-in-oil-in-water), solvent evaporation and diffusion method. Comminution was achieved by extrusion and the ethosomes were purified using centrifugation and solvent evaporation. Various ratios of phosphatidylcholine, BMV and cholesterol were used to synthesise ethosomal formulations. The ethosomes were analysed and characterised using: scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), dynamic light scattering (DLS) and Fourier-transform infrared spectroscopy (FTIR). Results: Extruded ethosomes loaded with BMV had a mean (n=3) hydrodynamic diameter (HdD) of 155.95±4.17 nm without cholesterol and 140±4.67 nm with cholesterol, and respective polydispersity indices (PdIs) of 0.22±0.02 and 0.19±0.02. The encapsulation efficiency (EE) was calculated as 75.21±4.14 % and 66.35±1.75 % respectively with a respective drug loading (DL) of 8.06±1.26 and 6.62±1.06 %. Conclusions: Ethosomes loaded with BMV were synthesised, analysed and characterised and may provide as promising as a model for transdermal drug delivery.

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Bioassay Guided Isolation of Angiotensin-Converting Enzyme Inhibitory Compound from Hypericum perforatum Marilyne Umugiraneza and Kenechukwu Obikeze

1School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 3367102@myuwc.ac.za

Introduction: Cardiovascular diseases are the leading cause of death globally, accounting for 31% of global deaths in 2016 with more than 75% of these deaths occurring in low-middle income countries. Hypertension has been identified as a major risk factors associated with most of cardiovascular diseases acquired during life. The renin angiotensin system largely contributes to the pathophysiologic process resulting in the hypertensive state through a sequence of reactions catalysed by the angiotensin converting enzyme (ACE) that result in the conversion of angiotensin I to angiotensin II the more potent vasoconstrictor and consequentially increasing blood pressure. Medications such as Angiotensin Converting Enzyme inhibitors and Angiotensin receptor blockers are developed to combat this process and numerous extracts and compounds from plants have been identified as in vitro ACE inhibitors. In this study, the aqueous extract of H. Perforatum commonly known as St John’s Wort was found to have significant ACE inhibitory activity and the compounds responsible for the observed inhibition will be identified. Methods: Plant extraction by maceration-1500g of H. Perforatum leaf powder was macerated, filtered, frozen and freeze dried to yield 90g of freeze-dried aqueous extract. ACE assay was performed at various concentrations to indicate the general percentage inhibition for the plant. Column chromatography was performed on the freeze-dried H. Perforatum extracts to separate its chemical components using various concentrations of hexane: ethyl acetate pre-indicated by TLC followed by a methanol washout. ACE assay was carried out on the various extracts obtained from the column to determine the extracts elution best suited for High Performance Liquid Chromatography (HPLC) and these will be characterized by NMR. Results: The aqueous extract of H. Perforatum was found to have a percentage inhibition ranging from 86-98% from lowest (1mg/ ml) to highest (200mg/ml) concentrations. The best column elution concentrations were found to be 9:1, 6:4 and 8:2 ethyl acetate: hexane and the final methanol wash out. These are further undergoing the ACE assay to determine their suitability for HPLC. Conclusions: The ACE inhibitory activity of the aqueous extract of H. Perforatum has been confirmed and compound separation by column chromatography has been successful. HPLC and NMR analysis are the next crucial steps in the identification of the ACE inhibitory compounds in H. perforatum.

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South African natural products as a potential source of new anti-parasitic drugs Achmat Kamies, Denzil R. Beukes

School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 3142124@myuwc.ac.za

Introduction: Parasitic diseases, such as malaria and Human African Trypanosomiasis (HAT), have been plaguing the world for centuries. HAT is on the World Health Organization’s (WHO) neglected disease list due to the lack of interest from “BIG Pharma” to develop drugs for this disease. HAT, also known as “sleeping sickness” is endemic in 36 sub-Saharan Africa countries. Malaria is one of the most common and life-threatening diseases in mainly tropical and sub-tropical areas in the world. There are currently more than 100 countries/regions around the world which are considered to be high risk malaria regions. The major challenge with these two parasitic diseases is that drug resistance has become a problem while, in the case of HAT, the therapeutic window is narrow, leading to significant side effects. The main aim of the project is to utilize South Africa’s vast marine and terrestrial biodiversity to find new lead compounds for these two parasitic diseases. Methods: Previous studies have suggested that marine carotenoids and cycloartane glycosides may have antiparasitic activity. Therefore, in the first part of this study we targeted the isolation of fucoxanthin (a carotenoid) from the marine alga Sargassum incisifolium and sutherlandioside D (a cycloartane glycoside) from Sutherlandia frutescens, using previously established protocols. In part two, we have developed a small library of marine extracts that will be screened for activity against Plasmodium falciparum and Trypanosoma brucei. The pure compounds were completely characterized by one- and two-dimensional NMR spectroscopy while the extracts were profiled by 1H NMR spectroscopy. Results: The 1H NMR spectrum of fucoxanthin showed a number of overlapping signals between dH 6 and 7 due to the polyene chain while the 13C NMR spectrum showed 40 carbon signals, including a characteristic signal at dC 202 due to the unusual allene group. The structure of sutherlandioside D was confirmed by observation of the mutually coupled olefinic methine signals at dH 5.8 and 6.3 and overlapping oxymethine signals at dH 3 and 4, due to the sugar moiety. Extraction and fractionation of the sponge voucher specimens led to a small library 24Extracts which are ready for biological testing. Conclusion: The carotenoid, fucoxanthin, and cycloartane glycoside, sutherlandioside D, were successfully isolated and characterized while a small library of marine sponge extracts was prepared.

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Selection, synthesis and evaluation of novel drug-like compounds from a library of virtual compounds designed from natural products with antiplasmodial activities Rostand Fankam Pokomi, Samuel Egieyeh, Sarel F. Malan, Jacques Joubert

School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 2918275@myuwc.ac.za

Introduction: New classes of medicine to combat malaria are urgently needed due to the surge in resistance of the parasite to antimalarial drugs. The identification of new scaffolds from natural products with in vitro antiplasmodial activities (NAA) can be an ideal starting point for the design and synthesis of novel antimalarial drugs with new mechanism(s) of action able to circumvent the problem of resistance. One interdisciplinary field which can aid in the discovery of novel chemical entities and ultimately the design of new drug-like molecules is cheminformatics. Methods: Cheminformatics was used as a computational approach for the design and selection of virtual compounds (VCs). These VCs were obtained from NAA retrieved from published articles, M.Sc dissertations, Ph.D theses, textbooks and other scientific resources. This was followed by prioritization of the VCs with the most promising anti-malarial activity from the library using KNIME (Konstanz Information Miner). KNIME is a computational tool for building and executing workflow using predefined parameters. A series of compounds were selected for synthesis based on the VC results, using multi-step procedures. Biological evaluation of synthesised compounds were conducted on both a sensitive and resistant strain of P.falciparum using a cell-based assay. Results: Using a KNIME workflow, we started with 164532 NAA compounds. Physicochemical parameters defining Lipinski’s rule of 5 were used as molecular descriptors to filter and prioritise the compounds. A total of 1805 VC were retained and the selection of a diverse set of compounds was done based on their fingerprints, in order to avoid the selection of compounds set in the same chemical space. Twenty-five molecules were selected for further chemical exploration and biological evaluation. The synthesised compounds were confirmed by NMR, MS and IR. Biological results indicated that these molecules were able to inhibit the malaria parasite in the low µM range. Conclusion: The objectives of the research included the selection, synthesis and evaluation of compounds retrieved from a library of VCs. This was made possible using a computational approach which allowed us to generate, select and develop new compounds with promising antimalarial activities.

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Rifampicin and Isoniazid minimum inhibitory concentrations in patients with drug-resistant tuberculosis Osaretin Christabel Okonji and Pierre Mugabo

School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

Background: The treatment outcomes of DR-TB are poor as compared to drug- susceptible cases. The current method used by the National Health Laboratory Science (NHLS) in South Africa is the phenotypic drug susceptibility test and the line probe assay for INH and RIF to determine drug sensitivity test. Mycobacterium tuberculosis is heterogeneous, that is it involves low, moderate and high level resistance. The MIC test can predict this level of resistance. The aim of this study was to determine the minimum inhibitory concentrations (MICs) of isoniazid (INH) and rifampicin (RIF) using the Bactec Mycobacterium growth indicator tube system MGIT 960. Method: The study population includes male and female patients, HIV-positive and HIV-negative, 18 to 65 years old, with confirmed MDR-TB (36), Rifampicin mono-resistance (12) TB and Isoniazid mono-resistant-TB (1). Sputum test result at the start of treatment was positive for all the isolates. The patients were treated with isoniazid, pyrazinamide, ethambutol, ethionamide, kanamycin, moxifloxacin, and terizidone. HIV-positive patients were also treated with: stavudine, lamivudine and efavirenz. We determine Isoniazid and rifampicin MICs distribution in 49 adult patients with DR-TB admitted to hospital for intensive treatment of DR-TB between March 2010 and October 2014). Forty-nine DR-TB Mycobacterium tuberculosis isolates were cultured. Drug susceptibility testing (DST) was performed using the Bactec Mycobacterium growth indicator tube system MGIT 960 for 49 DR-TB clinical strains of Mycobacterium tuberculosis. The MICs was defined as the lowest antibiotic concentration with less growth compared with the 1: 100 diluted controls. The data was analyzed using SPSS software version 25. Results: Of the 49 isolates cultured on MGIT, 17 (34.7%) patients had MICs below or at the critical concentration (CC) of 0.1 for INH. Eleven (22.4%) strains grew above the critical concentration of > 0.1 ≤ 1.0 ug/ml and therefore categorized as low-level resistance only 21(42.9%) isolates grew above > 1.0 ug/ml and therefore, were categorized as high-level-resistance to Isoniazid. The median MIC was 0.1ug/ml (IQR 0.1-1) and 0.5 ug/ml (IQR 0.5-2.875) for INH and RIF respectively. Seventeen (34.7%) patients had MICs below the CC of 1.0ug/ml for RIF. Most isolates 65.3% grew above the critical concentration (CC) > 1.0 ug/ml for Rifampicin Conclusion: Study objectives of this study were achieved. MIC distribution for INH and RIF was determined. Our results indicate that MICs testing for DR-TB patients at the start of the treatment is important or better than the current DST method. Some of our patients could still be treated with INH and RIF since some had MIC below or at the CC of 0.1 ug/ml for INH and 1.0 ug/ml for RIF. However, the different results obtained could also be due to bacterial changes due to treatment. MICs testing have great potential to shorten the time to sputum culture conversion and improve the treatment outcomes in DR-TB patients. Acknowledgement: South Africa Medical Research Council for financial support of the study.

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Non-compartmental analysis of Vancomycin Pharmacokinetics in Critically Ill Children Onyinye Akunne1, Pierre Mugabo1, Andrew Argent2,3

1School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa; 2Department of Paediatrics and Child Health, University of Cape Town; 3Paediatric Intensive Care Unit, Red Cross War Memorial Children Hospital, Cape Town, 7700, South Africa

E-mail-address: 3614460@myuwc.ac.za

Introduction Vancomycin is often used as the drug of choice in the treatment of bacteria that are methicillin resistant or in patients sensitive to penicillin. This study describes the pharmacokinetics of vancomycin in critically ill children. Methods Children aged one month to 16 years admitted to the paediatric intensive care unit of the Red Cross War Memorial Hospital and on vancomycin treatment for ≥24 hours and ≤72 hours were prospectively recruited. Blood samples were collected around predetermined optimal sampling times. A minimum of three samples per patients was analysed. Non-compartmental analysis was used to determine the volume of distribution (V), clearance (CL), half-life (t1/2), area under the concentration-time curve (AUC), elimination constant (Ke) and mean residence time (MRT). The minimum concentration (Cmin) and maximum concentration (Cmax) of vancomycin were measured directly as trough and peak plasma concentration respectively. Analysis of data was performed using PKNCA version 0.8.5 in R. Results/Discussion Forty-nine serum concentrations from 10 patients were included in the analysis. The ratio of male to female was 1:1. The number of patients per age group were as follows- <1 years = 5, 1 to 2 years = 0, 2 to 12 years = 3, >12 to < 16 years = 2. Median (range) age, weight and baseline serum creatinine (Scr) were1.6 (0.2-15) years, 10.6 (3.1-31.3) kg, 0.31 (0.15-0.78) mg/dL respectively. Patients received daily vancomycin doses ranging from 56 to 78 mg/kg. Mean (range) PK parameters were as follows: CL = 0.12±0.15 (0.018-0.52) L/h/kg, V =0.68±0.47 (0.15-1.57) L/kg, Ke = 0.147±0.073 (0.07-0.33) h-1, t1/2

=5.54±2.03 (2.11-9.62) h, MRT=8.02±2.92 (3.04-13.88) h, AUC =322.07±245.65 (31.6-850.4) mg/L.h, Cmin =6.21±3.66 (2.0-14.5) mg, Cmax =38.91±31.92 (10.4-97.2) mg. Trough concentration of 15-20mg and AUC >400mg/L.h of were not met in >80% and >75% of the patients respectively. Conclusions Variability in vancomycin pharmacokinetics was observed in patients. At current doses, target trough concentrations and AUC were not met.

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Synthesis and characterization of Isoniazid loaded mesoporous calcium carbonate microparticles Joseph Mitanda Mutenga1, Retsepile Ephraim Maphasa1, Nela Buchtová2, Marique Aucamp1,

Admire Dube1

1University of the Western Cape, School of Pharmacy, Bellville, South Africa; 2 CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France

E-mail-address : 3473992@myuwc.ac.za

Introduction: Tuberculosis (TB) remains a global problem killing 1.3 million people annually. Isoniazid (INH) like other anti-TB drugs is effective but its use is limited by toxicity, poor drug penetration and failure to deliver the right drug concentrations to target sites. Mesoporous calcium carbonate (CaCO3) microparticles have shown to be promising carriers for drugs due to their high porosity, biocompatibility, biodegradability and ease of fabrication. The aim of this study was to synthesize and characterize mesoporous CaCO3 microparticles loaded with INH that could be developed as inhalation medicines to treat TB. Methods: CaCO3 microparticles were prepared by direct mixing of equimolar volumes of aqueous solutions containing calcium ions and carbonate ions under different pH conditions using the glycine template method. Optimization studies were performed at different pH conditions. INH was loaded into the microparticles at the selected optimal pH through co-precipitation with the aqueous solutions prior to formation of microparticles and characterised for size and zeta potential (by dynamic light scattering), pore size (by Brunauer-Emmett-Teller (BET)), shape (by Scanning Electron Microscopy (SEM)), polymorphic transitions (stability tests and Differential Scanning Calorimetry (DSC), drug loading and release (by HPLC) and toxicity against RAW 264.7 macrophage cells. Results: Synthesis at pH 10 provided the optimal results and particles possessed an average size of 2.3 ± 0.3 µm for empty microparticles and a mean size of 3.1 ± 1.4 µm for INH loaded microparticles. The zeta potential was -18.17 ±1.56 and BET surface area was 100 m2/g for these particles. Most of the microparticles were spherical in shape and agglomerated by size. The particles were stable over a period of six months and were of the vaterite polymorph. The toxicity assay showed that microparticles were non- toxic against RAW 264.7 macrophages after 72 hours at a highest concentration of 1 mg/ml. Conclusions: INH loaded CaCO3 microparticles were synthesized and characterized and were non-toxic against macrophages. These particles are promising carriers for pulmonary TB drug delivery.

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Pulmonary delivery of anti-tuberculosis drug rifampicin loaded in surface-modified fourth generation PAMAM dendrimer as a novel drug delivery system Rami Ahmed1, Halima Samsodien1, Marique Aucamp1, Naushaad Ebrahim1 1School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail address: 3715701@myuwc.ac.za

Introduction: The aim of the research was to develop and explore the efficiency of surface-modified 4.0 G PAMAM dendrimer as a novel pulmonary delivery system of the anti-tuberculosis (TB) drug, rifampicin. Rifampicin was chosen for incorporation into the PAMAM dendrimer due to its hydrophobic nature and anti-tubercular activity. Methods: The PAMAM dendrimer having polyethylene glycol PEG (M.wt 2000 Da) content was synthesized using 4-nitrophenyl chloroformate as an activator and characterized using FTIR and 1H NMR analysis. Thereafter, rifampicin was loaded into the PEGylated dendrimers via a simple dissolution solvent evaporation method. Rifampicin loaded PEGylated 4.0 G PAMAM dendrimers were characterized using different analytical techniques namely, FTIR, DSC, 1H NMR, SEM, and DLS. The polymer encapsulation efficiency (EE%) and percentage 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. Results: The percentage coverage of 4.0 G PAMAM dendrimer peripheral with PEG was achieved in a range of 38-100%. Drug-loaded nanoparticles displayed a relationship between the degree of dendrimer PEGylation, nanoparticles size, zeta potential, EE%, and DL%. FTIR and 1H NMR data showed that the majority of rifampicin molecules were encapsulated within the dendrimer cavity. SEM images 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 PEGylation, the slower release rate was observed with higher PEGylated dendrimers. Overall, prolonged release behaviour was noticed in comparison to non-PEGylated dendrimer and free drug. Conclusions: PEGylated 4.0 G PAMAM dendrimers were suggested as a suitable drug carrier having superior features and prolonged release properties for the anti-TB drug, rifampicin compared to the non-PEGylated dendrimer.

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Investigating the interaction between the Hsp90 inhibitor, novobiocin, and human serum albumin by STD NMR Julian Sheldon1, Edith M. Antunes2, Denzil R. Beukes1

1 School of Pharmacy, 2 Department of Chemistry, University of the Western Cape, Robert Sobukwe Road, Bellville, 7535

Introduction: Nuclear magnetic resonance spectroscopy (NMR) is a specialised tool that allows for the study of molecular interactions within solution. There are various experiments that an NMR machine is able to perform, all in the purpose of confirming a chemical structure or identifying possible binding epitopes. The ability for this to occur arises from the fact that the experiments allow researchers to characterize events of molecular interactions at an atomic level (Swann et al., 2010). For this, Saturation transfer difference NMR (STD-NMR) has been used in order to characterise ligand-receptor complexes. STD-NMR takes advantage of the nuclear Overhauser effect to allow for the observation of ligand resonance signals involved in receptor binding. STD-NMR like many other experiments may inform researchers of some form of chemical interaction a small molecule may have with its receptor. What sets STD-NMR apart from the rest is that it provides specific information on the protons of a small molecule that are either directly involved or very close to the interaction site (within 5Å). Novobiocin is an aminocoumarin antibiotic known to interact with bacterial proteins by inhibiting the ATP binding site on DNA gyrase (Jara, Corral and Arch, 2016). There have been previous studies which also show its interactions with human serum albumin (HSA) by various means as HSA plays an integral role in the transport of many drugs which influences their plasma concentrations and therapeutic efficacy. Novobiocin has many interactions with proteins but to the best of our knowledge no study has been performed that show any form of specific binding interactions Novobiocin has with HSA. It is the aim of this study to confirm the binding epitopes of Novobiocin to HSA with STD-NMR. Methods: 5µM solutions of each ligand (Novobiocin, Warfarin, Ibuprofen) were made up in DMSO-d6 to perform the model study on a Bruker Avance 400MHz spectrometer. A ligand: protein ratio of 20:1 in a 5mm NMR tube, 80µL of each ligand + 200 µL HSA + 220 µL deuterated Phosphate Buffer Saline (PBS) pH 7.5 were added and ran STD. All STD experiments were run with the zgesp water suppression experiment Results: We successfully determined the binding epitopes of novobiocin to HSA by STD-NMR. At the 1:20 protein-ligand ratio, Novobiocin is seen to bind to sudlow site I and 2 by interfering with the binding of Warfarin and Ibuprofen (known HSA binders). Conclusion: STD-NMR can be used to determine binding of ligands to proteins as well as determine the specific binding epitopes involved in the binding process.

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In Silico ADMET profiling of Phytochemicals isolated from Leonotis Leonurus Chioma Uduma1, KenechukwuObikeze1, Samuel Egieyeh1

1School of Pharmacy, University of the Western Cape, Bellville, 7535, South Africa

E-mail-address: 3758537@myuwc.ac.za

Introduction: Leonotis leonurus contains a number of phytochemicals (small molecules) that have been reported as “Hits” from various bioactivity screens. These small molecules may be developed into potential drug candidates. The conventional process of drug development requires a lot of resources hence the need for in silico ADMET prediction prior to such venture. in silico ADMET profiling can be used prior to the process of in-vitro preclinical bioassay to identify small molecules from activity screening that may have promising desirable drug-like and pharmacokinetic properties. It also allows the identification of small molecules with potential pharmacokinetic liabilities and prospects for “Hit” to “Lead” optimization. This study utilizes in silico methods to predict pharmacokinetic properties of 36 bioactive small molecules extracted from Leonotis leonurus, a plant widely used in Southern Africa in the treatment of various illness. Methods: A thorough search of Google Scholar for literature on compounds isolated from Leonotis leonurus was carried out using the terms ‘Leonotis leonurus’ AND ‘ Ethnobotanical uses’ AND ‘Bioactive Compounds’. The structures and SMILES of known compounds were obtained from PubChem or were drawn in 2D and 3D using ChemDraw Pro16.0 and ChemDraw 3D 16.0 respectively. The collated structures were imputed into the online ADME prediction side www.swissadme.ch to predict the pharmacokinetics, drug likeness and medicinal chemistry property of the compounds.QikProp by Schrodinger and the online web tool biotransformer.ca were used to predict the metabolism pathway of these compounds. The results were then analyzed using data analytic software. Results: A total of 15 out of the 36 phytochemicals were predicted to have good absorption profile, were non-toxic. These same set of compounds may not inhibit Cytochrome P450 isoenzymes and may not undergo first pass metabolism therefore they would maintain their activity when given orally. Conclusion: This study identified promising phytochemicals with desirable ADMET properties without the expense of in-vitro assays. These phytochemicals can be further studied for their mechanism of reported pharmacological activities and may be ultimately developed into drug candidates.

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Descriptive and retrospective evaluation of empiric carbapenem-sparing regimens versus carbapenem antibiotics use in non-intensive care adult patients at Khayelitsha District Hospital (KDH) Isaac Mugoya; Michelle Viljoen; Renier Coetzee; JJ Taljaard; GL Muntingh; M Saal

University of the Western Cape, School of Pharmacy, Bellville, 7535, South Africa

E-mail-address: 3173170@myuwc.ac.za

Introduction: Antimicrobial resistance is an increasingly global concern with escalating morbidity and mortality rates due to the development of multidrug resistant organisms which are seemly difficult-to-treat or even impossible to eliminate with currently available antimicrobials. Carbapenem-resistant Enterobacteriaceae (CRE) are among multidrug resistant organisms where overuse of carbapenems is believed to be the driving force for their existence. This study aimed to evaluate Carbapenem and a Carbapenem-sparing regimen use and looked at patient health outcomes. Methods: Stock transaction reports of Carbapenems and Carbapenem-sparing regimen were extracted retrospectively (1 March - 31 August 2018) from KDH using an electronic medicine management (JAC electronic software). Patient folder numbers were acquired for adult patients to investigate and access specific clinical information on the Enterprise Content Management and National Health Laboratory Service systems. Patient records which complied with the set inclusion criteria were included and data was manually recorded onto a data collection tool before it was transcribed onto an electronic data base. Results: A total of 220 patients’ folder was accessed for inclusion, 121 did not fit the criteria and 99 were included in the final data base. The females presented 53.5% of the study population and the mean age was 46 years with a standard deviation of 15.48 for both female and males. Initial hospital diagnosis varied from hospital acquired infections to community acquired infections. Hospital acquired pneumonia was the dominating diagnosis made during this period and Human immunodeficiency virus (HIV), tuberculosis (TB) and diabetes mellitus (DM) were the most common co-morbidities recorded. Conclusion: The researchers initially experienced unexpected delays to access data hence more detailed results will only be available once full data analyses have been completed.

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List of completions 2018 and 2019 April 2018

Name Degree Project title Ms Somaya Almajdoub

MPharm Polymer coating of an optimized nano lipid carrier system of Harpagopytum procumbens extract for oral delivery

Ms Lynn Randall MSc Pharmacy Administration

The use of complementary and alternative medcines in the treatment of menopausal symtoms by private healthcare patients in Pretoria, South Africa

Miss Modupe Abaniwonda

MSc Pharmaceutical Science

Polycyclic compounds as carriers for neuroactive non-steroidal anti-inflammatory drugs.

Miss Mofenge Yvette MSc Pharmaceutical Science

Novel adamantine-chloroquinoline conjugates to overcome Plasmodium falciparum

Dr. Emmanuel Kabali

MSc Pharmacy Admin

Review of the effectiveness of the medicines regulatory system in Zambia over the period 1995 to 2015

Ramadan Swead MSc Pharmacutical Science

The development of a study protocol, and ethics and regulatory approval documentation, for evaluation of clinical efficacy of Sutherlandia frutescens in adult type 2 diabetes

Ireen Denya MSc Pharmacutical Science

Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzhemer's disease

Mrs Suad Ebdiwi Mpharm A comparative in vitro analysis of anti-infective generic and brand medicines in th African public

Ms Nyasha Guzha MPharm Development of a model to predict the cost of management of cancer with chemoth

Mrs Veleeni Ramburan

MPharm Integrating complementary and alternative medicines into pharmacy: identifying ch in meeting

August 2018 Miss Miriam Mhlanga

MPharm A Pharmacy perspective on the epidemiology of antimicrobial drugs in the Kuilsriver area.

Ms Mookho Lerata MSc Pharmaceutical Sc

Discovery of cytotoxic natural products from South African marine sponge.

Ms Maboleng Sekhonyana-Khetsekile

MPharm The development and preparation of the quality control dossier for registration of A afracapsule

Ms Michelle Kent MSc Pharmacy Administration

Investigating the economic impact of mandatory electronic prescribing requirements in the United States.

Mr Mohamed Khalil MSc Pharmacy Administration

Pharmacoeconomic evaluation in Egypt and its role in the medicine reimbursement.

Ms Olivia Bishop Lekuni

MSc Pharmacy Administration

Cost effectiveness of selecting an enantiopure formulation over a racemic mixture compound.

December 2018 Mr Bernard symon Phd A Reductionistic epistemology utilizing brain laterality which

investigates pharmacists’ ideal interactive environment.

Mr Edmund Mabande

MSc Pharmaceutical

Antimicrobial discovery from South African marine algae.

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Science Ms Evelyne Alonjang

MSc Pharmaceutical Science

Active encapsulation of diclofenac sodium into liposome for opthalimic preparations.

April and August 2019

April 2019 Mr Shavani Pillay MSc Pharmacy

Administration Evaluation of reporting all types of adverse drug reactions by parents of children younger than 18 years in South Africa.

Rensche Mayne MSc Pharmacy Administration

Community pharmacist’s knowledge, attitude and practices on adverse drug reaction reporting in South Africa.

Mr Frank Zindo PhD Pharmaceutical Science

Polycyclic propargylamine derivates as multifunctional neuroprotective agents.

Mr Yves Tchakounte MPharm Design and evaluation of fast dispersible tablets of lamivudine using selected natural superdisintegrants

Mr Lovette Tenghe MPharm Formulation, evaluation and comparison of polymeric micelles for improved oral delivery of tenofovir disoproxil and zidovudine using poly-lactic-co-glycolic acid nanoparticles.

Ms Onyinye Mokwelu

MPharm Bioassay guided isolation of an ace inhibitory compound from hypericum perforatum.

Mr Tumelo Modau MSc Pharmacy Administration

The availability of persons nominated for adverse drug reporting and associated challenges in Gauteng regional and district public hospitals.

Mr Brighton Chawatama

MSc Pharmacy Administration

Knowledge-based integration of Zimbabwean traditional medicines into the national healthcare system: A case study of prostate cancer.

Ms Jennifer Hockin MSc Pharmacy Administration

Knowledge, Perceptions and Practices of Risk-Based Monitoring among clinical trial practitioners in the United States.

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List of new postgraduate students 2019

Surname First Names Degree

AFROGHEH NAZANIN MPharm

KWIZERA DIEUDONNEE MPharm

MUNYAYI PRUDENCE VIMBAI MPharm

MUSAFILI NGABO YVES MPharm

MOMATH SAAJIDA MSc Pharmaceutical Science

OSELUSI SAMSON MSc Pharmaceutical Science

UDODONG ABRAHAM SAM MSc Pharmaceutical Science

LERATA MOOKHO PhD

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Notes

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