Formulation development of extended and immediate release tablets using extrusion-based 3d printing technology

Abstract

Fused deposition modelling (FDM) based 3D printing technology for oral solid dosage form has shown promising results in the fabrication of individualized tablets compared to conventional method. However, the main concern of this technique is the quality of drug loaded filament including mechanical properties such as flexibility, stiffness and brittleness. To cope with these problems, filaments were produced via hot melt extrusion (HME) by screening and characterizing a series of pharmaceutical mixtures (6 types of polymers and 5 types of disintegrants) and processing parameters for specifying the design space in Design of Experiment (DoE). Therefore, the purposes of the present study were to develop and optimize the extended and immediate release FDM printed tablets using DoE. Solid state characterizations of extruded filaments and printed tablets were performed to understand the critical material and process attributes. The results showed that hydroxy propyl cellulose (HPC)-blended filaments can significantly improve their flexibility. All manufactured filaments and tablets possessed adequate quality attributes such as physicochemical, rheo-mechanical properties and desired drug release profiles. Further, the effect of formulation compositions on drug release and the optimized formulation were investigated by the statistically D-optimal mixture design. The optimized formulation of extended release tablets composed of 10% IMC: 49.5% HPC: 19.09% PVP/VA: 20.94% SLP which resulted in the desired drug release at 4, 12 and 24 h while that of immediate release tablets contained 30% THY: 35% EPO: 20% HPC: 15% SSG with 85% drug release within 30 min. Consequently, this study suggested that the formulation development of oral drug delivery with the required drug release pattern can be achieved by a quality by design approach which could be extended to other HME-FDM applications in pharmaceutical area.