Development of a dual extrusion printing technique for an acid- and thermo-labile drug

Abstract

Over the last years fused deposition modeling has been increasingly considered as a game-changing technique for the preparation of individualized pharmaceutical products. Until now investigations have mainly focused on dosage forms loaded with very stable drugs or model substances. Going beyond this early stage of research, developers will also have to deal with more challenging active substances. In this work different printing designs for tablets containing the acid- and thermo-labile drug pantoprazole sodium were tested. Initial dual extrusion printing of a cellulose acetate phthalate coat and a tablet core of polyethylene glycol 6000 with 10% (m/m) pantoprazole sodium resulted in thermal degradation of pantoprazole at cellulose acetate phthalate printing temperatures of 141 °C. Therefore, different tablet designs were developed. The sectioning of the design of the tablet coat in a gastro-resistant cellulose acetate phthalate bottom part and an upper nearly insoluble polycaprolactone part printed at only 58 °C was suitable to prevent visible signs of thermal degradation. Dissolution testing indicated also no drug loss during dual extrusion printing. However, printed enteric tablets with shell thicknesses of 0.4 to 0.5 mm were not completely gastro-resistant. Drug release at intestinal pH values was delayed compared to uncoated cores. In conclusion, 3D-printing of gastro-resistant tablets containing thermo- and acid-labile drugs seems in principle possible. However, it remains an unsolved challenge to meet United States Pharmacopeia requirements.

Keywords: 3D-printing; Enteric tablet; Fused deposition modeling; Hot-melt extrusion; Pantoprazole sodium.