## 3 Results and Discussion
Figure 5: (**a**) Illustrative scheme of the chemical treatment received by the hybrid filaments (dimethylamino-lamino group of the molecule acquiring an H+ proton); (**b**) image of the E100, E100/Hsp(\(-\)) and E100/Hsp(\(+\)) filaments (under bending); and (**c**) sample of continuous and complete E100 filament obtained via hot-melt extrusion at 130 \({}^{\circ}\)C.  
The equality of means hypothesis test demonstrated that there is no significant difference in the average diameter of the cross sections of the produced filaments (95% confidence level), with or without drug addition, both for low or high levels of available drug mass. This is an indication that these filaments do not show significant changes in volume per unit length, after the introduction of variable amounts of the drug. This last analysis is important for the purpose of the research because it demonstrates that the filaments produced with or without additives do not show significant variation in the surface area in contact with simulated gastrointestinal fluid solutions for in vitro release tests. Thus, the temporal variation in drug concentrations released in these media (initially available in the volume of the filament) will be directly related to the pH-dependent nature of the polymer and with the mass of drug available in the bulk of the filament (proportional to its length). This proportionality and the homogeneous disposition of the drugs in the filaments are important factors for the production of pharmaceutical solid solutions printed with different geometries and replicable formulations [30]. Figure 7 presents the X-ray diffractograms (XRD) of the filament samples and of the drug Hesperidin (Hsp). The diffractogram for the pristine E100 filament type exhibits the usual amorphous characteristic of the copolymer in its original form, with a broad  
Figure 6: SEM micrographs of the (**a**) model drug Hesperidin (Hsp), and (**b**) E100, (**c**) E100/Hsp(\(-\)) and (**d**) E100/Hsp(\(+\)) filaments. peak in the 20 range of 12-27\({}^{\circ}\)[31; 32]. On the other hand, the spectrum of the pure Hsp demonstrates the typical crystalline nature of the drug, with narrow and intense peaks at specific 20 in the analyzed range (at 12.4\({}^{\circ}\), 13.8\({}^{\circ}\), 15.7\({}^{\circ}\), 16.4\({}^{\circ}\), 19.8\({}^{\circ}\), 21.4\({}^{\circ}\), 22.5\({}^{\circ}\), and 24.9\({}^{\circ}\)) [33; 34; 35]. The XRD spectrum of the E100/Hsp(\(-\)) filament sample shows the amorphous predominance of the polymer, as previously discussed. The specific diffractogram demonstrates that the characteristic peaks of the crystalline phase of Hsp do not appear explicitly in the spectrum, due to the use of a small proportion of the drug in comparation to the mass of E100 in this sample and/or the appearance of the amorphous phase of the Hsp. In addition, detailed zoomed portions of Figure 7, (1) and (2), show the existence of two diffraction peaks of the drug in the E100/Hsp(\(-\)) filaments, at angles 20 = 12.4\({}^{\circ}\) and 21.4\({}^{\circ}\), indicating the presence of Hsp in the composite. The XRD spectrum of the E100/Hsp(\(+\)) filament has its baseline shifted to higher intensities, following the curvature of the E100 spectrum, in the range 20 = 12-27\({}^{\circ}\). In this same range, there are peaks that were previously detected in the Hsp spectrum, which indicates the presence of the crystalline phase of the drug in the filament. These results represent a first indication that the E100 pH-dependent characteristic and the pharmacological properties of Hsp are maintained by the filaments after the hot-melt extrusion process. FTIR spectroscopy was used as a tool for detecting molecular vibrations in the materials used in the filaments production.