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. / LG2018