This work aimed to obtain an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone® (PVP/VA), Klucel ELF® (HPC) and Soluplus® (SOL) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an E-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas infrared spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9% and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations.