26 research outputs found
Three dimensional printed controlled release tritherapeutic tablet (3D CRTT) for the delivery of anti-HIV drugs
A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy,
Department of Pharmacy and Pharmacology, University of the Witwatersrand,
Johannesburg, 2017.Numerous pharmaceutical solid dosage form manufacturing techniques have emerged over the years and among them, 3D-Printing (3DP) has emerged as a highly attractive and versatile approach. 3DP is a cutting edge technology set to expand and revolutionize tablet manufacturing among various other applications in industry. The study reported in this thesis focuses on developing a humic acid-polyquaternium-10 (HA-PQ10) 3D-Printable ink for the delivery of three anti-HIV bioactives, efavirenz (EFV), tenofovir (TDF) and emtricitabine (FTC). HA was strategically employed based on its capability of entrapping both hydrophilic and hydrophobic drugs. PQ10 contributed towards the system’s swellability in aqueous media. The HA-PQ10 PEC was responsible for retarding drug release therefore it behaved as a drug reservoir. Validation of HA-PQ10 complexation was carried out by synthesizing the HA-PQ10 polyelectrolyte complex (PEC) in aqueous media at pH 6, 7 and 8. The complexation yielded fibrilla and porous PECs. The PEC formation was attributed to ionic interactions between the quaternary ammonium centres (PQ10) and carboxylic groups (HA). The PECs were determined to be amorphous in nature and exhibited good biocompatibility when tested for cytotoxicity in human adenocarcinoma cell line (Caco2). The model drug, efavirenz (EFV) was loaded into HA-PQ10 using the complexation-precipitation (C-P) technique. The resultant EFV-loaded HA-PQ10 was compared to benchtop extrudates manufactured using the extrusion-spheronization (E-S) process. Assessment of the EFV saturation solubility and intestinal permeability showed EFV solubility and permeability enhancement of 14.14±2.81% and 61.24±6.92% respectively. The properties were compared to those of a marketed comparator product. Loading RTV into the optimized HA-PQ10 further validated the solubility and permeability enhancing properties in the BCS class IV drug as well. The extrudates performed superiorly compared to the formulation synthesized by C-P. The E-S technique was utilized to optimize HA-PQ10 based on drug release and intestinal permeation enhancement. The optimal HA-PQ10 was employed for 3DP of EFV-loaded HA-PQ10 into an oral tablet formulation. It was imperative to add cellulose acetate phthalate (CAP) to enhance the 3D-Printability of the HA-PQ10. CAP made the synthesized delivery system pH responsive and drug release results showed that most of the release occurred under intestinal conditions. The EFV-loaded 3DP tablet was compared to a tablet synthesized by direct compression. 3DP was more porous, less dense and more swellable than the direct compression tablet. These remarkable differences were attributed to the tableting method. 3DP leads to the formation of solid bridges between particles as the sludge (ink) undergoes extrusion and drying process. The direct compression technique involves axial powder compaction at high pressures which force particles to interact through Van der Waals forces or hydrogen bond formation. High drug loading of EFV was achieved and the tablet was further optimized to manufacture the ‘controlled release tritherapeutic tablet’, CRTT, a fixed dose combination (FDC) consisting of EFV, TDF and FTC. In vivo studies were conducted in large white pigs and CRTT absorption was compared to a marketed FDC, Atripla®. There was sustained release of EFV, TDF and FTC from CRTT and this was validated by the long residence times determined from pharmacokinetic analysis. EFV was maintained within the therapeutic index of the drug during the 24 hour study. Through this study, 3DP proved to be a technology with potential for manufacturing novel formulations. As more research is underway in the 3DP field, it can only be appreciated that its scope of use will continue to grow and restructure pharmaceutical manufacturing processes.LG201
HIV and AIDS Prevention Programmes in Zimbabwe: A Gendered Terrain
Efforts to curb the HIV and AIDS epidemic have reached a deadlock. This emanates from the manner in which gender has been understood in these programmes. Gender has not been tackled in all its complexities that is to include men and children. It is therefore unfortunate that gender has been epitomised as a women’s issue. In these gender discourses men are given two or three lines. The ostracisation of men in the domain of HIV and AIDS related issues have created dangerous gaps that has made it difficult for the epidemic to be combated. The paper observed that for HIV and AIDS to be thoroughly dealt with, there must be concerted efforts from both men and women. Feminist theologians should desist from blatantly attacking men as the perpetrators of HIV and AIDS for within these men lies great potential to fight the HIV and AIDS epidemic. The paper in light of social constructionism, literature review and in-depth analysis contends that proper gender equality is a necessity in the battle against HIV and AIDS
The ‘hard-wearing pharmaceutical industry’ that is thriving in the midst of a pandemic
Black and grey markets for pharmaceuticals are thriving during the Covid-19 pandemic, especially in low- and middle-income countries, and this is a worrying public health concer
Investigation of Theophylline Release Kinetics from Carbopol 940P Sustained Release Matrix Tablets
The hydrophilic matrix material, Carbopol 940P, has not been extensively investigated for drug release as the other polymers such as Carbopol 971P and 934P. The present study was aimed at investigating the release kinetics of a highly soluble drug, theophylline, from Carbopol 940P only without the addition of any other ingredient or excipient. Drug release from these matrices was analysed according to Higuchi, first order and zero order release kinetics. At low drug loading (20 %), release was mainly diffusion-controlled as the release pattern was best explained by square root of time kinetics (Higuchi mechanism). However, at higher drug loading (30 % and 40 %), constant release rates were obtained as shown by zero order kinetics explaining the release data best. Constant release rates are most desirable with controlled or sustained release devices. This ensures that constant drug levels in the blood/body are achieved. Carbopol 940P demonstrated that it is applicable in the fabrication of a controlled release matrix that is simple, easy to prepare and cost effective
Risks to the community pharmacists and pharmacy personnel during COVID-19 pandemic:perspectives from a low-income country
Coronavirus disease 2019 (COVID-19) is an infectious disease that has become a global pandemic. COVID-19 is spreading in Africa, and Zimbabwe has not been spared. The cases in Zimbabwe are mainly from imported cases due to high volume of travellers from the COVID-19 hotspots. In Zimbabwe, local transmission is also anticipated due to inter- and intracity travelling. Frontline health workers are at risk of infection due to contact with infected people as they discharge their duties. In this setting, the risk to community pharmacists and pharmacy personnel is poorly understood and characterised. This paper looked at the risks of infection that are peculiar to community pharmacy personnel and suggested some recommendations to reduce the risk to COVID-19 infection
Self-Assembled Multivalent (SAMul) Polyanion Binding – Impact of Hydrophobic Modifications in the Micellar Core on DNA and Heparin Binding at the Peripheral Cationic Ligands
This paper reports a small family of cationic surfactants designed to bind polyanions such as DNA and heparin. Each molecule has the same hydrophilic cationic ligand, and a hydrophobic aliphatic group with eighteen carbon atoms with either one, two or three alkene groups within the hydrophobic chain (C18-1, C18-2 and C18-3). Dynamic light scattering indicates that more alkenes lead to geometric distortion, giving rise to larger self-assembled multivalent (SAMul) nanostructures. Mallard Blue and Ethidium Bromide dye displacement assays demonstrate that heparin and DNA have markedly different binding preferences, with heparin binding most effectively to C18-1, and DNA to C18-3, even though the molecular structural differences of these SAMul systems are buried in the hydrophobic core. Multiscale modelling suggests that adaptive heparin maximises enthalpically-favourable interactions with C18-1, while shape-persistent DNA forms a similar number of interactions with each ligand display, but with slightly less entropic cost for binding to C18-3 – fundamental thermodynamic differences in SAMul binding of heparin or DNA. This study therefore provides unique insight into electrostatic molecular recognition between highly charged nanoscale surfaces in biologically-relevant systems
Enantiomeric and Diastereomeric Self-Assembled Multivalent Nanostructures : Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA
A family of four self-assembling lipopeptides containing Ala-Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16-l-Ala-l-Lys/C16-d-Ala-d-Lys) and (C16-d-Ala-l-Lys/C16-l-Ala-d-Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self-assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d-lysine ligands, with a further slight preference for attachment to l-alanine, with the CMC being irrelevant
The role of prophecy in Zimbabwean socio-economic transformation: the case of Ezekiel Guti
Perhaps the most enduring legacy of the Old Testament prophets is in the area of economic engagement as Elisha’s ministry speaks volume. In Zimbabwe, Ezekiel Guti has championed. This paper focuses on the economic engagement of the prophet Ezekiel Guti in his bid to improve the lives of the underside of history and how this resonates with the prophetic vocation of Elisha. The paper, through canonical approach, typological comparative analysis, and literature review contends that the prophet Ezekiel Guti is a quintessence to demonstrate that the engagement of prophets in economic initiatives is vital in contemporary times.Keywords: prophet, socio-economic transformation, talent