The aims of this work were to produce immediate release printed tablets using fused deposition modelling (FDM) technique and to systematically explore the effects of different compositions on drug release by Quality by Design approach. Screening studies of various drug loadings and excipients were conducted by hot melt extrusion and FDM printing to set up the appropriate limit of each independent factor (critical material attribute, CMA) in Design of Experiment. This study demonstrated that the use of polymeric mixture containing different theophylline loadings (10, 30 and 60% w/w) in combination with multiple pharmaceutical polymers (hydroxy propyl cellulose (HPC), Eudragit® EPO, Kollidon® VA 64) and disintegrant (sodium starch glycolate) were successfully hot melt-extruded and FDM printed with no plasticizer. Rheological measurement was performed to understand the critical process parameters (CPP) while the mechanical property of extrudable and printable filaments was investigated by 3-point test for the formulation development. Surprisingly, HPC were found to be superior as a flexibility modifier in all printable filaments. A range of pharmaceutical characterizations were examined to ensure the critical quality attributes (CQA). Characteristic dissolution profiles were obtained. D-optimal mixture design of 17 formulations suggested that theophylline release was considerably affected by the combined action of different excipients and could predict the optimum formulation with the required quality target product profile (QTPP) in pharmacopoeia (85% release at 30 min). Therefore, this can be a useful platform to develop immediate release products for a specific group of patients commercially.