Research and development of a delayed release 3D printed hydrocortisone tablet

Abstract

3D printing is a technique that can be utilised in the making of personalised medicine as opposed to the one size fits all traditional mass production of medicine. In the case of rare diseases, it can be beneficial for the patients to have a better alternative to their therapy where it fits more to their need. This is the case for patients with Addison’s disease. Currently there is an unmet medical need because they are being treated with a suboptimal form of hydrocortisone therapy, since it does not replicate the circadian rhythm of cortisol. In healthy individuals, serum cortisol builds up during the night and slowly decreases during the day. The current therapy is a hydrocortisone regimen of 3 tablets a day during the day, meaning that there is no build-up of hydrocortisone during the night, leaving patients with a low quality of life and morning illness. The aim of this research is to formulate a delayed-release formulation of hydrocortisone. This will be done using hot-melt extrusion and fused deposition modelling 3D printing techniques. This formulation has to adhere to the rules and regulations of the European Pharmacopoeia and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. For the hot-melt extrusion, the temperatures used were 110°C for the initial temperature and 60°C for the final temperature. The printing temperature was set at 110°C. Two separate filaments were created for the tablet. One was the hydrocortisone filled core and one for the shell, without hydrocortisone, with the desired delayed effect. The results showed that the FJ8 hydrocortisone formulation, extruded and printed at 110°C, does not have any impurities ≥0.20% threshold, stipulated by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The dissolution of the tablet was also tested with a variety of shell formulations, however none were able to replicate the desired 4-hour delayed release profile. The creation of a complete tablet was not achieved at this time, but the core of the duo-tablet did adhere to the rules and regulations around impurities. Further researched is needed to find a suitable shell formulation in order to create the tablet with the desired release profile.