## 3 Results and Discussion
It is possible to verify that both samples with pharmaceutical form have a profile of rapid and complete release of Hsp in an acid medium; however, the polymeric matrix is shown as a device to protect the drug in a basic medium. This behavior is like that of the polymer in its original form, confirming that the extrusion process does not change the characteristics of the copolymer for usage as a filament in the release of active principles applications. This rapid dissolution of the Hesperidin in acid medium, considering the diffusion of the drug along cylindrical matrices [48], can be conveniently modeled by the Weibull function (continuous lines in the graph),  
\[\frac{C_{t}}{C_{\infty}}=1-\exp\left(-at^{b}\right) \tag{1}\]  
where \(C_{t}\) and \(C_{\infty}\) represent the drug concentrations in the medium at time t and the final time, respectively, \(a\) represents a time scale parameter, and \(b\) represents the dissolution kinetics degree. The drug release from the E100/Hsp(\(-\)) and E100/Hsp(\(+\)) matrices returned the value of \(b=1\), showing exponential kinetics, typical of delivery systems with a rapid drug-release response. Thus, while the total release of the drug is reached in approximately 30 min in the simulated gastric fluid, for both concentrations tested, the release of the active principle in the intestinal fluid is minimized, even with a longer analysis time interval. These results prove the pH-dependent characteristic of E100 (drug protection in basic media and dissolution in acidic media) are retained when in the form of 3D printing filaments. It is important to highlight that the polymer release profile is not interfered with by protonation. Protonation interferes with the flexibility of the filament, based on the best molecular arrangement in the polymer chain, as discussed. In addition, a pharmaceutical solid solution model part (10 mm in diameter and 3 mm in height) was designed in a CAD environment (Figure 12a) and then printed (Figure 12b) using the E100/Hsp(\(-\)) filament (arranged on a Kywoo3D Tyocon commercial direct drive 3D printer). The part was printed using Repetier Host slicer software v. 2.2.4, with a grid-type infill pattern (18 layers, 60% inner density), extrusion temperature of 130 \({}^{\circ}\)C, and printing time of 4.5 min. Figure 12: (**a**) CAD project of the pharmaceutical solid solution model part, produced from E100-Hsp(\(-\)) filaments; (**b**) 3D printed part; (**c**) inner circular section of the part, in the sixteenth layer of filament deposition; and (**d**) distribution of Hesperidin particles into E100 matrix. The regular diameter and flexibility of the filament, in addition to the printing settings in the slicer software, were suitable for the layered material deposition process to occur, without clogging the printing system (due to possible filament breaks), and with physical reproduction of the designed part. Figure 12c shows the circular section of the sample, in the sixteenth layer of molten filament deposition. In this layer, it is possible to observe the inner infill pattern, with the formation of parallel lines spaced apart across the entire section of the object. This configuration is repeated throughout the entire interior of the part, forming a grid-like structure, as projected in the slicer software. At the edge of the section, it is also possible to observe a continuous portion of the area filled with molten material as a result of the beginning of the transition from 60% filling density of the internal sections to a total filling of the object area in the eighteenth layer (sample surface). Figure 12d shows a detail of the characteristic dispersion of the drug in the printed part, with a regular particle size distribution below 2 um. This result indicates that the largest particulate aggregates of Hesperidin tend to decrease considerably in size upon interaction with the polymeric matrix, which favors the bioavailability of the active ingredient.