Patient-focused programable release indomethacin tablets prepared via conjugation of hot melt extrusion (HME) and fused depositional modeling (FDM)-3D printing technologies

Indomethacin (IND) eases the chronic pain caused by Juvenile idiopathic arthritis (JIA) in clinic, but it was reported that it has dose-related side effects such as gastrointestinal irritations and potential damage to nervous system. So, there is a considerable demand for offering effective, safety, and quality IND dosages for individual pediatric and youth patients. The main aim of this work is to on-demand manufacture personalized and programmable release IND tablets via combining hot melt extrusion (HME) and 3D printing technologies based on the structure-release correlations. IND loaded filaments were extruded and then the tablets were designed and printed. A series of physical and chemical characterization studies were also conducted, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage polarized light microscopy (PLM), texture analysis, and in vitro drug release studies. The results showed that IND was dispersed in HPMCAS matrix and formed amorphous solid dispersions (ASDs). Additionally, the in vitro drug release studies demonstrated that the release of IND can be programmed via manipulating 3D structure design. The mathematical model to predict the IND from structural designed tablets was obtained and two tablets (T-v1 and T-v2) were printed to validate such model, where the fitting coefficient are 0.9964 and 0.9965, respectively. This study suggested that combining HME and 3D printing technologies could be an optimal approach for personalized and precision drug delivery dosage development.