Preparation of orodispersible films using semisolid extrusion 3D printing: A versatile manufacturing approach
Abstract
Orodispersible films (ODFs) emerged as a patient-friendly dosage form that is particularly suitable for pediatric therapy, where swallowing difficulties often interfere with adherence to therapy. In this study, the preparation of ODFs using semi-solid extrusion (SSE) 3D printing was investigated as an alternative to the conventional solvent casting method. Four hydrophilic polymers – hydroxypropyl cellulose (HPC), polyethylene glycol-polyvinyl alcohol graft copolymer (PVA-PEG), maltodextrin (MDX) and sodium alginate (SA) – were used either individually or in binary blends, with caffeine selected as the model active ingredient. Films were printed on an Ultimaker 2+ system and evaluated for uniformity, thickness, porosity, moisture content, mechanical strength, disintegration and drug release. Formulations containing only MDX or PVA-PEG exhibited poor printability due to leakage and spreading, while other systems showed reproducible film deposition and satisfactory dimensional stability. Binary blends generally resulted in increased film thickness. SA-based films showed the lowest porosity and moisture absorption, while HPC films exhibited favorable mechanical properties. The investigated samples achieved rapid disintegration and complete release of the caffeine. These results confirm the potential of SSE 3D printing as a versatile manufacturing platform for customizable ODFs that enable precise dosing and patient-centric design for pediatric drugs.
References
European Pharmacopoeia Commission. European Pharmacopoeia. 11th ed, Strasbourg: Council of Europe, 2022.
Jacob S, Boddu SHS, Bhandare R, Ahmad SS, Nair AB. Orodispersible films: current innovations and emerging trends. Pharmaceutics. 2023;15(11):2753.
Ianno V, Vurpillot S, Prillieux S, Espeau P. Pediatric formulations developed by extrusion-based 3D printing: from past discoveries to future prospects. Pharmaceutics. 2024;16(4):441.
Turković E. Orodispersible films – pharmaceutical development for improved performance: a review. Therapie. 2022;77(6):567–80.
Özcan-Bülbül E. Preparation and characterization of orodispersible films: a review. AAPS PharmSciTech. 2024;25:2938.
Teoh XY, Zhang B, Belton P, Chan SY, Qi S. The effects of solid particle containing inks on the printing quality of porous pharmaceutical structures fabricated by 3D semi-solid extrusion printing. Pharm Res. 2022;39(6):1267–79.
Paccione N. Development of personalized dexamethasone orodispersible solid oral dosage forms by semisolid extrusion 3D printing. Int J Pharm. 2025;660:122198.
Zhang B. An investigation into the effects of ink formulations of semi-solid extrusion 3D printing on the performance of printed solid dosage forms. J Mater Chem B. 2024;12(16):3700–12.
Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical and bioadhesive properties. J Pharm Pharm Sci. 1999;2(2):53–61.
Preis M, Gronkowsky D, Grytzan D, Breitkreutz J. Comparative study on novel test systems to determine disintegration time of orodispersible films. J Pharm Pharmacol. 2014;66(8):1102–11.
Turković E, Vasiljević I, Drašković M, Obradović N, Vasiljević D, Parojčić J. An investigation into mechanical properties and printability of potential substrates for inkjet printing of orodispersible films. Pharmaceutics. 2021;13(4):468.
Mehta KA, Kislalioglu MS, Phuapradit W, Malick AW, Shah NH. Effect of formulation and process variables on porosity parameters and release rates from a multi-unit erosion matrix of a poorly soluble drug. J Control Release. 2000;63(1–2):201–11.
Janigová N, Elbl J, Pavloková S, Gajdziok J. Effects of various drying times on the properties of 3D printed orodispersible films. Pharmaceutics. 2022;14(2):250.
Abdella S, Kim S, Afinjuomo F, Song Y, Upton R, Garg S. Combining the potential of 3D-printed buccal films and nanostructured lipid carriers for personalised cannabidiol delivery. Drug Deliv Transl Res. 2024;14:984–1004.
Eslami M, Elkoun S. Alginate-based hydrogels and films: recent advances in crosslinking mechanisms, mechanical properties and biomedical applications. Molecules. 2023;28(18):6637.
Kibar EAA, Us F. Starch–cellulose ether films: microstructure and water resistance. J Food Process Eng. 2017;40(2):e12382.
Elbl J, Veselý M, Blaháčková D, Ondruš J, Kulich P, Mašková E, Mašek J, Gajdziok J. Development of 3D printed multi-layered orodispersible films with porous structure applicable as a substrate for inkjet printing. Pharmaceutics. 2023;15(2):714.
Drašković M, Turković E, Vasiljević I, Trifković K, Cvijić S, Vasiljević D, Parojčić J. Comprehensive evaluation of formulation factors affecting critical quality attributes of casted orally disintegrating films. J Drug Deliv Sci Technol. 2020;56:101614.
Shojaee Kang Sofla M, Mortazavi S, Seyfi J. Preparation and characterization of polyvinyl alcohol/chitosan blends plasticized and compatibilized by glycerol/polyethylene glycol. Carbohydr Polym. 2020;232:115784.
Vlad RA, Pintea A, Coaicea M, Antonoaea P, Rédai EM, Todoran N, Ciurba A. Preparation and evaluation of caffeine orodispersible films: the influence of hydrotropic substances and film-forming agent concentration on film properties. Pharmaceutics. 2023;15(5):1376.
