Orodispersible films (ODFs) are increasingly employed for individualized drug delivery due to their ease of administration and precise dosing. However, their drug loading capacity is often limited by the need to maintain thin, flexible structures, posing a particular challenge for incorporating poorly soluble drugs. This study aimed to develop and characterize porous ODF matrices optimized for 3D printing of medicated inks. The primary objective was to investigate the impact of macroporosity on the dissolution kinetics of both poorly soluble and readily soluble drugs, with a focus on enhancing the release of the poorly soluble dexamethasone. Porous ODFs were fabricated via solvent casting using silica- and silicate-based porogens, then loaded with caffeine or dexamethasone through 3D printing. The films were comprehensively characterized using structural (micro-CT, BET), mechanical, and solid-state techniques (SEM, Raman microscopy, FTIR, XRD) to assess porosity, drug crystallization behavior, and drug-matrix compatibility. Drug release was evaluated through dissolution studies. Silica-based porogens yielded films with tunable macroporosity, supporting high drug loads (up to 3-5 times the ink volume). Dexamethasone printed on the SY2 substrate exhibited markedly enhanced dissolution (79.2 ± 1.8%) compared to its powdered form (29.9 ± 11.5%), achieving 61.5% release within 20 min. In contrast, caffeine (readily soluble) showed a transient reduction in dissolution rate during the initial two minutes, attributed to increased particle size and delayed film disintegration. Overall, integrating porous matrix design with 3D printing significantly improved the dissolution of poorly soluble dexamethasone without inducing drug-matrix interactions, confirming that structural modifications drive the enhanced release.

Department of Pharmaceutical Technology Faculty of Pharmacy Masaryk University Palackého třída 1946 1 Brno 61200 Czech Republic

Department of Pharmacology Toxicology and Immunotherapy Veterinary Research Institute Hudcova 10 Brno 62100 Czech Republic

Institute of Pharmaceutics and Biopharmaceutics Faculty of Mathematics and Natural Sciences Heinrich Heine University Düsseldorf Universitätsstraße1 Düsseldorf 40225 Germany

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacky University Olomouc Šlechtitelů 27 Olomouc 783 71 Czech Republic

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