Eudragit E100/Hesperidin 3D Printing Filaments: Preparation, Characterization, and In Vitro Release Studies  
[PERSON]  
1 Research Group on Electrospinning and Nanotechnology Applications (GPEA-Nano), Department of Materials Science, Federal University of Sao Francisco Valley, Juazeiro 48902-300, Brazil; [EMAIL_ADDRESS]  
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2 Laboratory of Pharmacy, Department of Botany, Federal University of Santa Catarina, Florianopolis 88040-535, Brazil; [EMAIL_ADDRESS]  
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3 Formulation & Application Services--Health Care Department, Evonik Brasil Ltd., Sao Paulo 04711-904, Brazil; [EMAIL_ADDRESS]  
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4 Research and Extension Center, Laboratory of Fuels and Materials (NPE/LACOM), Department of Chemistry, Federal University of Paraiba, Campus I, Joao Pessoa 58051-900, Brazil; [EMAIL_ADDRESS]  
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5 Electrical and Computer Engineering Department--CEMPRE, FCTUC, Polo 2, University of Coimbra, 3030-290 Coimbra, Portugal; [EMAIL_ADDRESS]  
Footnote 1: email: {c.c.v.edu, c.v.  
solutions with personalized and reproducible geometries and dosages, for application in controlled drug delivery systems [9; 10; 11; 12; 13]. Regarding the research and development of alternative and functional polymers for controlled drug release, Eudragit\({}^{\text{\textregistered}}\) E 100 (E100) can be highlighted, whose solubility depends on the pH of the medium [14]. It is a synthetic acrylic thermoplastic copolymer with good mechanical strength, and is biocompatible, biodegradable, and safe for human oral administration [15]. This copolymer is already known as a polymeric matrix for protecting active substances and for masking the taste and odor of drugs, which facilitates their use when these characteristics become inconvenient for the user. Its cationic nature helps promote its rapid solubility only at low gastric pH (acidic, below 5.0). This intrinsic solubility is possible due to the hydration of the dimethylamino groups of its molecule, which causes these units to become protonated (acquire an H\({}^{+}\) proton), leading to the repulsion of these groups along the polymeric chain in continuous contact with the medium. With protonation, these functional groups interact with anions present in the gastric fluid to form salts, which drastically decreases the stability of the original molecule and breaks the copolymer chain [16; 17]. On the other hand, in media with a basic pH, the copolymer molecule tends to become immobilized, and consequently the polymeric chain is impeded from flowing freely. The E100 copolymer has been used in the pharmaceutical industry as a functional polymeric matrix (in homogeneous mixtures of the polymer with drugs) in pH-dependent pharmaceutical forms for oral administration, such as tablets, capsules, discs, and spheres. In addition, research over the last decade has explored the use of polymers in the form of films, ophthalmic solutions, sprays, and transdermal and vaginal implants [18; 19; 20]. Its importance in programmed release formulations is also justified by the fact that this polymer can increase the dissolution rate and bioavailability of poorly water-soluble drugs, while improving the physical stability of amorphous solid dispersions [14]. In this sense, the search for alternative dosage forms with E100, which are more efficient for encapsulation, transport, and controlled release of drugs in the gastrointestinal tract, is currently an open field of research in materials and pharmaceutical technology. Although the importance of this copolymer is recognized in the industry as a coating and protection of active substances, and even in research for the development of micro/nanostructures for drug delivery [21], works that deal with the development of filaments of E100 for 3D printing of customized pharmaceutical solid solutions are still incipient in the literature [22; 23].