The main production challenges of this copolymer are linked to the the ability to manufacture filaments that are workable and functional, both during the filament molding process in extruder machines, and/or during the use in conventional 3D printers available on the market. The low flexibility and brittleness (rupture with low deformation), due to the cylindrical shape necessary for its use (high length compared to the diameter of the circular section), makes the continuous printing process of the designed pharmaceutical solid solution difficult. Quality control of the E100-based filaments production using a hot-melt extrusion (HME) technique also involves thermal stability studies of the polymer in interaction with additives, since the process involves heating the material at high temperatures (generally, above 100 \({}^{\circ}\)C). It is known in the literature that the mass loss of the E100 influenced by temperature begins above 200 \({}^{\circ}\)C, with complete material degradation occurring above 300 \({}^{\circ}\)C [24; 25; 26]. For example, temperatures in the range of 110 to 130 \({}^{\circ}\)C have previously been used for the development of E100/drug filaments containing various graft additives, using HME [26]. In that invention, the temperature of 140 \({}^{\circ}\)C was also used in the printing process of E100 pharmaceutical solid solutions. [PERSON] et al. studied the addition of varying amounts of tricalcium phosphate (Ca\({}_{3}\)(PO\({}_{4}\))\({}_{2}\)) and triethyl citrate (C\({}_{12}\)H\({}_{20}\)O\({}_{7}\)) to E100, as an inert graft material and plasticizer, respectively [22]. The authors reported that the optimized mass proportions of the materials were 46.75:3.25:50.00 of the copolymer, triethyl citrate, and tricalcium phosphate, respectively, for the preparation of filaments without drug addition, and of 46.75:3.25:37.50:12.50 of the same materials, for the preparation of filaments with the addition of 12.5 wt% of the drug. In the study conducted by [PERSON], [PERSON], and [PERSON] [23], considerable amounts of magnesium silicate (MgSiO\({}_{3}\)) and triethyl citrate were used as additives. Triethyl citrate was used for the same purpose, as reported in the work by [PERSON] et al. [22]. Magnesium silicate was used as an anti-adherent agent so that the copolymer would not adhere to the walls of the extruder tube during the hot melt extrusion process. With the presence of these additives, the mass of active principle per volume of filament (in mg/cm\({}^{3}\)) was also automatically reduced. In this context, this work aims at the preparation and characterization of 3D printing cylindrical filaments of the Eudragit E100 copolymer, containing variable amounts of the Hesperidin (Hsp) model drug (flavonoid, with antioxidant and anti-inflammatory properties), and respective in vitro controlled release tests of the active molecule, from the E100 matrix. The E100/Hsp hybrid filaments were produced using hot-melt extrusion (HME), and then they were subjected to a surface chemical protonation treatment, free of chemical additives. The microstructural characterization of the filaments was performed using SEM, XRD, FTIR, and ATR techniques, while the thermal analysis of the materials was performed using DSC. The mechanical behavior of the samples was evaluated from flexion tests in a universal testing machine. The in vitro Hsp controlled release tests were carried out in simulated gastro and intestinal solutions, with the aim of obtaining the temporal variation in the relative concentration of Hsp released in these fluids. The results showed filaments with uniform diameter which were able to preserve the polymer and the drug molecular structures after the extrusion process. In addition, it was noted that the protonation process was able to improve the flexibility of the E100 filaments, compared to those produced without chemical treatment.