3D printed hydrogels for oral personalized medicine

Universidad del Pais Vasco, Thesis 2021

3D printing has become a promising and revolutionary pill-making technique for the pharmaceutical industry, enabling a relatively low-cost personalized medicine. Fused deposition modelling, also known by its initials FDM, is the most affordable technology for this goal, printing the material by a layer-by-layer deposition. However, the pressure assisted microsyringe technique is more adequate for working with drug containing inks as it does not need high temperatures, preventing the drug degradation. However, to make this goal possible, high accuracy and reproducibility is required, avoiding trial and error procedures. Thus, a correlation between rheology, printing parameters and the printed object was investigated. This way predicting the printing process just by looking at the materials rheology can be achieved. In fact, even though there are a lot of oral drug delivery and 3D printing related articles, there are only a few that focus on the relation between the rheology and the printing conditions of the sample. Thus, this thesis will try to expand this research area. As the basis of this thesis hydrogels containing different drugs were selected. Hydrogel formulations with two different bases have been prepared, one based in polyethylene glycol and the other one based in glycerol. In addition, carboxymethyl cellulose and water were present in all the mixtures prepared by mixing the components with different concentrations. The drugs contained within are atenolol and hydrochloric thiazide (HCTZ), both being antihypertensive drugs. The preparation of the formulations was simple and it could easily be translated to other drugs and scaled-up. It has been shown that glycerol-based compositions have better rheological properties for the pill making purpose. The effects of atenolol and HCTZ on the prepared hydrogels were studied as well as the relation between the drugs and the polymeric matrix with the final objective of printing a multicomponent formulation, also called polypill. Finally, the morphology of the 3D printed objects has been examined after the consolidating process and after a pH test and lyophilization. This way the effect of the stomach’s acidic environment on the drug delivery systems has been studied. The contained carboxymethyl cellulose (CMC) was supposed to have a pH responsive behaviour collapsing under acidic environments. But it has been shown by morphological characterization that it is not suitable for this purpose. Even though they showed that they do not fit their purpose of protecting the drug at acidic conditions, rheological studies and the 3D printing process for glycerol-based formulations showed that they have good shape fidelity to the CAD design. Improving such formulations could lead to good resolution pills that fit the purpose of protecting the incorporated drug from degrading at the acidic pH of the stomach. A personalized medicine could be achieved by such formulations.