Doctor Pharmaceuticae - DPharm

Permanent URI for this collectionhttps://hdl.handle.net/10566/14968

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Evaluation of the cardioprotective effect of Centella asiatica compounds.
(Univesity of the Western Cape, 2024) Ajani, Temitope Akinwumi; Obikeze, Kenechukwu
Reactive oxygen species (ROS) are highly reactive and toxic by-products of cell metabolism. Biological systems are equipped with endogenous antioxidant enzymes to manage the level of ROS in the system as they can be both beneficial (for cellular redox signalling) and deleterious (involved in the initiation and progression of inflammatory diseases). In a situation where ROS production exceeds antioxidant enzyme levels, oxidative stress is experienced. This has been implicated in the initiation of atherosclerosis, which is a risk factor for coronary artery diseases and other cardiovascular-related diseases. Coronary artery disease and other related diseases are responsible for 50% of all cardiovascular diseaserelated mortalities. Hypoxia, radiation, and other factors promote the production of ROS in cardiac cells where the endogenous enzymes become overpowered. This results in the progression of cardiovascular diseases (CVDs) via various processes along the pathophysiological pathway. One of such process is the breakdown of collagen and elastin responsible for the tensile strength of heart tissue by the proteolytic enzyme cathepsin S (CatS). The approach in the past to reduce oxidative stress and the progression of oxidative stress-related CVDs has been to supplement with antioxidant molecules and biologics that mimic endogenous antioxidant enzymes like superoxide dismutase (SOD). The purpose of this study was to identify compounds from Centella asiatica with the ability to improve SOD enzyme activity, while inhibiting CatS activity, to improve CVD outcomes. Centella asiatica extracts were prepared using hexane, dichloromethane, chloroform, ethanol, ethyl acetate, methanol, acetonitrile and distilled water. The phytochemical constituents of the extracts were determined, and antioxidant activity was evaluated using the DPPH assay. The cytotoxicity of the most promising extracts (ethanol, ethyl acetate and acetonitrile) was then evaluated by MTT assay.
Community pharmacist and adolescent relationship in Johannesburg: use, knowledge and attitudes regarding emergency contraceptive pills
(University of the Western Cape, 2010) Lutz, Steven; Butler, Nadine C
Community pharmacy in the 21st century has become more patient and disease orientated. Consequently, South African community pharmacies are inundated with queries from the public for advice and treatment on a wide variety of medical conditions, including use of ECPs. Although community pharmacists are often the first port of call for Emergency Contraceptive pills (ECPs), limited practitioner-patient skills and insufficient knowledge often hinder pharmacists from providing the necessary clinical management. Central to this research undertaking were two primary goals: Determination of the knowledge of community pharmacists regarding ECPs; when and how these drugs may be used, the adverse effects, safe sexual practice and spread of STls including HIV/AIDS, pharmacists' attitude towards dispensing these drugs to adolescents and their willingness to counsel, discuss and educate the adolescent members of the community. To determine gender, age, present education level at school, race and religion of adolescent respondents and to ascertain both under each demographic, as well as overall, at which age teenagers felt it was appropriate to engage in sexual activity, their knowledge of ECP drugs and use thereof, from where these may be obtained, as well as their attitude towards community pharmacists. Questions were added to determine knowledge on alternate forms of sexual activity, 5Tls including HIV / AID5 and finally to determine whether they believe that they have been adequately educated on these topics. A total of 149 completed questionnaires were received from 278 surveys which were previously e-mailed to community pharmacists registered in Johannesburg and surrounding areas, and were analysed (54% response rate). Results showed that pharmacists' knowledge that these drugs have no effect on established pregnancy, that no situation exists where these drugs are absolutely contra-indicated, and knowledge of frequency of ECP use permitted, among others, were lacking. Furthermore, results showed that only 54% of pharmacists routinely discuss use of regular contraceptives with teenagers requiring ECPs, only 24% discuss the contracting of 5Tls including HIV/AID5, and 14% of pharmacists only advise on use and adverse effects of 5Tls if the adolescent asks. A total of 1950 questionnaires were sent out to schools for voluntary completion by teenage learners, of which 1346 were returned completed (69% response rate). Almost 30% of adolescent respondents did not know what these drugs were used for, less than 13% knew that they should be ingested as soon as possible after coitus and maximally within 72 hours (in terms of the drug registration), and 32% believed or were unsure if these drugs could prevent 5Tls or HIV. A large proportion of teenagers were reluctant to discuss use of ECPs with any pharmacist and an even larger proportion with their regular family pharmacist. They also showed a distinct lack of knowledge in alternative forms of sexually activity. However, only 32% of respondents believed their training in sex education to be insufficient. Pharmacists are frequently called upon to provide ECP treatment, but their knowledge is limited and could certainly be improved upon perhaps by utilizing CPO programs. They also need to be properly trained in how to deal with the younger members of the community, in order to create a professional yet caring attitude, and encourage adolescents to feel confident of the advice they will receive, yet comfortable in seeking their advice. Adolescents' sexual behaviour should not be morally judged by members of the healthcare team, which makes the teenager feel self-conscious and uncomfortable in discussing their problems. They could doubtlessly benefit from further and improved education via the media, properly-trained educators and the medical fraternity, including community pharmacists. This would doubtlessly have a noticeably positive effect on high levels of unwanted teenage pregnancies and on the contracting of 5Tls including HIV/AID5 which is so prevalent in South Africa.
Population pharmacokinetics of ethionamide and ethionamide sulfoxide in patients with multidrug-resistant tuberculosis
(University of the Western Cape, 2025) Boulou, Fanya
Tuberculosis (TB) remains an infectious disease worldwide and the leading killer of people living with HIV; yet it is curable. One of the challenges faced in TB therapy is the resistance of Mycobacterium tuberculosis to antituberculosis drugs, leading to drug-resistant tuberculosis (DR-TB). Various types of DR-TB resulted from antimicrobial resistance; up-to date, multidrug-resistant tuberculosis (MDR-TB) is the predominant type of DR-TB, thus the focus of the current study. MDR-TB developed following resistance of the Mycobacterium tuberculosis to rifampicin and isoniazid, which are the two most potent first-line antituberculosis drugs. It is currently treated with a choice of regimens: a short, all-oral 6-month regimen, a 9-month all-oral regimen containing ethionamide, and longer individualized regimens. Ethionamide needs to be activated by mycobacterial enzymes to exert its antimicrobial activity. Ethionamide sulfoxide, its active metabolite, displays a similar or greater activity against Mycobacterium tuberculosis; yet there is limited pharmacokinetic literature on ethionamide sulfoxide, unlike ethionamide which has been studied for more than five decades. This study aimed at determining the population pharmacokinetics of ethionamide and ethionamide sulfoxide, assessing the effect of HIV status, antiretroviral drugs, age, weight, gender, and renal and hepatic functions on their respective pharmacokinetic parameters. The study also aimed at determining the amount of ethionamide sulfoxide that emanated from ethionamide metabolism in the body. Methods: After signing an informed written consent, male and female patients with MDR- TB, co-infected or not with HIV, who were on treatment for at least two weeks at Brewelskloof Hospital (Western Cape, South Africa), were involved in the study. On the day of the study, after an 8-hour overnight fast, each patient received his/her medications, including 500 mg or 750 mg dose of ethionamide as determined by the doctor in charge. Blood samples were collected at baseline and 1, 2, 2.5, 3, 3.5, 4, 5, 8 and 24 h post drug administration. Using a developed and validated ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS), ethionamide and ethionamide sulfoxide were simultaneously quantified in patients’ plasma. Ethionamide and ethionamide sulfoxide pharmacokinetic parameters were first determined through non-compartmental analysis (NCA) using PKanalix2023R1 and compared.
Antimicrobial efficacy of Helichrysum spp. on post-harvest diseases of pomegranate fruit
(University of the Western Cape, 2024) Matrose, Albertina Neliswa; Obikeze, Kenechukwu
Fungal pathogens are the major contributors to losses of horticultural produce, which poses a threat to the global food security. The solution to reducing food decay caused by fungal pathogens mainly relies with crop and plant protection which include the aggressive usage of chemical fungicides and other cost-effective postharvest strategies which are associated with significant health, safety, and environmental implications. Numerous investigations have been undertaken on the effects of crude plant extracts as safe, cost-effective, and yet effective strategies for post-harvest management of fungal pathogens. According to Gurjar et al. (2012), under stressful conditions, plants strategically generate secondary metabolites for their defence strategy against predators. Some of these compounds have been tested and proven to exhibit intense activity against numerous fungal pathogens. This study aimed to utilize in vitro and in vivo of Helichrysum odoratissimum and Helichrysum patulum to identify potential bioactive compounds that can be used as alternatives fungicidal agents to synthetic chemicals for post-harvest management of Botrytis cinerea. Moreover, the influence of geographical harvest location, extraction solvent types, and processing methods were investigated. Detailed literature search on the plant extracts and natural compounds as potential alternative treatment for post-harvest fungal pathogens was performed.
Selected polyols as co-formers for pharmaceutical solid dispersions
(Universty of the Western Cape, 2024) Poka, Madan Sai; Aucamp, Marique
Poor aqueous solubility is a major concern for most new chemical entities (NCEs) developed for oral drug delivery as well as for almost 70% of registered and already marketed drugs. Solid-state alterations such as solid dispersions (SDs), co-amorphous and co-crystal systems have taken the lead over the past two decades, in an effort to address the challenge of poor drug solubility. One of the common factors amongst these techniques, that play a significant role in solubility enhancement, is the type of carrier or co-former used. Low molecular weight excipients such as amino acids, citric acid and a few sugars were studied as potential co-formers. However, the efforts made in identifying new low molecular weight excipients were modest. Given their low molecular weight, safety, hydrophilic nature and having high hydrogen bonding propensity makes polyols an interesting option to be explored as carriers.
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.
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.
Investigation of suitable microencapsulation techniques in the preformulation of selected antiretroviral drugs
(University of the Western Cape, 2022) Okafor, Nnamdi Ikemefuna; Aucamp, Marique
Background: The use of antiretroviral drugs (ARVDs) in the treatment of HIV/AIDS have been promising and effective especially amongst adults as it suppresses the viral load, thereby improving the life expectancy of HIV patients. However, the adoption of the treatment amongst children living with HIV have proved to be challenging. This is because of the poor drug adherence or non-compliance resulting from the lack of child-friendly formulations. The dosage forms are typically large tablets which have led to difficulty in swallowing or needs breaking of the tablets to obtain the correct dose and potentially some sort of dosage form manipulation by mixing it with milk or juice. The limited paediatric formulations that are available are mostly unpalatable, despite being formulated in a syrup or liquid, it still presents with a bitter taste. Therefore, all these factors combined have emphasized the need for child friendly dosage forms for children suffering from this debilitating disease.
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.
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.
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.
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.
Pharmacological characterization and chemo-informatics analysis of compounds from leonotis leonurus
(University of Western Cape, 2021) Oghenetega, Chioma O N; Obikeze, Kenechukwu
The central nervous system (CNS), consisting of the brain and the spinal cord, is responsible for integrating sensory information and influencing most bodily functions . The CNS is protected from toxic and pathogenic agents in the blood by permeability barrier mechanisms. These barrier mechanisms, specifically the blood brain barrier (BBB) presents a challenge for the discovery of CNS active drugs as it is requirement for these drugs to permeate the BBB to reach their target site in the CNS. The conventional processes of drug design and discovery from natural products are time consuming, tedious, expensive and have a high failure rate. It has been reported from various studies that the use of computational modelling and simulations in drug design and discovery is less costly and less time-consuming with a greater chance of success than the conventional processes. The process of drug discovery and design can, therefore, be easily carried out using proven computer models, software, and web-based tools .
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.
Pharmacological Characterization and Chemo-informatics analysis of Compounds from Leonotis leonurus.
(2021) Chioma O N, Oghenetega; Obikeze, Kene
The central nervous system (CNS), consisting of the brain and the spinal cord, is responsible for integrating sensory information and influencing most bodily functions . The CNS is protected from toxic and pathogenic agents in the blood by permeability barrier mechanisms. These barrier mechanisms, specifically the blood brain barrier (BBB) presents a challenge for the discovery of CNS active drugs as it is requirement for these drugs to permeate the BBB to reach their target site in the CNS. The conventional processes of drug design and discovery from natural products are time consuming, tedious, expensive and have a high failure rate. It has been reported from various studies that the use of computational modelling and simulations in drug design and discovery is less costly and less time-consuming with a greater chance of success than the conventional processes. The process of drug discovery and design can, therefore, be easily carried out using proven computer models, software, and web-based tools . As a result of the above stated facts, this study aims to utilize in silico as well as in vitro methods in identifying and characterizing promising druglike bioactive compounds from Leonotis leonurus with Central Nervous System (CNS) activity, more specifically in treating Alzheimer’s disease (AD).
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
Pharmacist educational outreach for improved primary care of asthma in children
(University of the Western Cape, 2001) Bheekie, Angeni; Zwarenstein, M F
Underdiagnosis and undertreatment of asthma in children are barriers to optimal health care delivery and health, incurring substantial costs to both the families and health services. A tailored multifaceted educational outreach intervention ("academic detailing") was designed and implemented among private sector general practitioners (GPs) serving a poor working class urban community in Cape Town, South Africa. The intervention aimed to improve primary care childhood asthma by promoting the adoption of guideline-based key messages. The effectiveness of the intervention was tested in a randomised controlled trial, Chestiness and Asthma in Mitchell's Plain (CHAMP) (Zwarenstein 1999). This thesis describes the design, implementation and qualitative evaluation of the outreach intervention. Methods Qualitative interviews and quantitative sample surveys were conducted among GPs to identify and measure the prevalence of perceived barriers to optimal asthma care in children. A trained pharmacist visited GPs twice, promoting eight evidence-based primary care messages to overcome barriers to optimal care for asthma in children. The messages focused on key diagnostic indicators, a treatment algorithm based on severity, cost of drug therapies, inhaler and spacer use, and preventive treatment. These messages were formatted into attractive promotional material. The first visit promoted use of the messages, the second reinforced adoption in routine practice and assessed GPs' responses using unobtrusive qualitative data collection methods. The dialogue was tailored to each GP's needs. Results Thirty-two GPs received the intervention. All but one consented to both visits. At the first visit responses were varied. A few GPs were confused or suspicious; most were in agreement with the messages but seemed passive towards implementation; a few were keen to adopt the messages into their routine practice. Response at first visit was not predictive of use as assessed at the second. At the second visit, most GPs claimed that they personally agreed with and used the messages, with a large minority less enthusiastic. Conclusion The intervention appears to have been broadly accepted as evident from GPs' acceptance of the outreach pharmacist, but reports of complete adoption of the messages and use of the kit were less prevalent. This finding is consistent with and helps to explain the improved health outcomes of children with asthma in the CHAMP trial. The combination of qualitative and quantitative research methods was effective in identifying and assessing GPs' barriers. Further, the combination helped to confirm the determinants for the intervention. Unobtrusive qualitative methods provided valuable insight into GP behaviour in routine setting. Additional studies conducted in public sector pnmary care settings and for other diseases are needed to confirm the wider acceptability and effectiveness of multifaceted outreach interventions aimed at improving professional practice. Such an intervention in our study setting seemed successful for childhood asthma.
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.
An investigation of the production of non-coated sustained release beads by extrusion and Spheronization
(University of the Western Cape, 1995) Pather, Sathasivan Indiran; Russell, Irina
The popularity and increasing complexity of sustained release dosage forms has resulted in increased costs to the patient. One approach to achieve cheaper, yet effective, sustained release medication is through the simplification of production processes. Matrix tablets have been used to sustain the release of numerous drugs and are cheap to prepare. Since they are single-unit dosage forms, however, they display less predictable transit through the gastrointestinal tract. Hence, they provide less reliable blood levels of the drug in comparison with multi particulate dosage forms. Of the various types of multiparticulates available, pellets are popular for oral administration. A fairly recent innovation, in pelletization technology, is extrusion and spheronization. With this technique it is possible to produce pellets with a high degree of drug loading directly and rapidly. The drug loaded beads are usually coated for a sustained release effect. If one could omit the coating step, it would avoid many problems (thus reducing the number of quality control procedures required) and save chemicals, labour and capital for the purchase of additional equipment. The primary aim of this project was to investigate the preparation of non-coated, spheronized sustained release pellets, while a secondary aim was to prepare beads that can be compressed into sustained release tablets. A tablet can accommodate a larger mass and the compaction forces involved may enhance the sustained release effect. Several techniques were used in an attempt to sustain the release of drugs of different solubilities. In one series of formulations, a novel method was used to incorporate a binder consisting of ethylcellulose in ethanol. Using this technique, the release of Theophylline was sustained for approximately 8 hours. In other formulations, several materials were added to beads with the aim of forming sustained release matrixes. Only magnesium stearate was able to prolong the release of Acetaminophen and Theophylline for a reasonable time. In an attempt to explain why materials that were successfully used in sustained release matrix tablets were of very limited value in beads, an equation was developed to calculate the approximate distance between the retardant particles. Calculations using this equation revealed that the retardant particles were too far apart, within each bead, to expect consolidation to occur. The discrete retardant particles do not retard drug release effectively. Eudragit?-containing beads, which sustained the release of the drug to a small extent, were successfully compressed into tablets, both on their own and in combination with non pareil seeds. In each case, the sustained release effect was improved by compaction. In the case of the products manufactured with non pareil seeds, the tablets disintegrated rapidly to release the beads, thus ensuring that the advantages of multiparticulates were maintained. Because it was realised that a large amount of the matrix material could not be incorporated within the beads if a high dose drug was formulated with Avicel? PH 101, the idea of forming the matrix outside the beads was developed. Several materials were tried in an attempt to form a sustained release external matrix. Eudragit? RSPO prolonged the dissolution of Theophylline for more than four hours. Magnesium stearate was able to sustain the release of Acetaminophen and Theophylline appreciably. In the latter case, the dissolution, in water, of a standard adult dose of the drug was prolonged for more than 12 hours. However, the dissolution in an acidic medium was much faster. The described technique represents an advance in extrusion and spheronization technology. While beads containing Cutina? HR did not show promise as sustained release units, they compacted to form sustained release tablets of good appearance and acceptable strength. These tablets were considered to have been efficiently prepared because the constituent beads were easily manufactured and showed good flowability, and because a glidant and a lubricant were not required. The production of sustained release Indomethacin beads with a more steady release profile than the innovator's product has also been described in other experiments. The research described in this thesis represents progress towards the widespread commercial production of effective non-coated sustained release beads and may encourage further work towards this goal.
Selected antiretroviral and anti-tuberculosis drug combinations by non-covalent bonding
(University of Western Cape, 2021) Ngilirabanga, Jean Baptiste; Samsodien, Halima
Treatment of the human immunodeficiency virus (HIV) and tuberculosis (TB) infections have become very complicated due to the advent of drug resistance. Drug combinations offer an alternative approach to reducing the emergence of drug resistance. Pharmaceutical co-crystals have provided the pharmaceutical industry with the ability to optimise the physicochemical properties of active pharmaceutical ingredients (APIs) while preserving the biological activity. Pharmaceutical co-crystals are formed between APIs and suitable co-formers that are biologically safe or even a second or third API.

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