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

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.

Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug.

PURPOSE: Dissolution speeds of tablets printed via Fused Deposition Modeling (FDM) so far are significantly lower compared to powder or granule pressed immediate release tablets. The aim of this work was to print an actual immediate release tablet by choosing suitable polymers and printing designs, also taking into account lower processing temperatures (below 100°C) owing to the used model drug pantoprazole sodium. METHODS: Five different pharmaceutical grade polymers polyvinylpyrrolidone (PVP K12), polyethylene glycol 6000 (PEG 6000), Kollidon® VA64, polyethylene glycol 20,000 (PEG 20,000) and poloxamer 407 were successfully hot-melt-extruded to drug loaded filaments and printed to tablets at the required low temperatures. RESULTS: Tablets with the polymers PEG 6000 and PVP K12 and with a proportion of 10% pantoprazole sodium (w/w) demonstrated a fast drug release that was completed within 29 min or 10 min, respectively. By reducing the infill rate of PVP tablets to 50% and thereby increase the tablet porosity it was even possible to reduce the mean time for total drug release to only 3 min. CONCLUSIONS: The knowledge acquired through this work might be very beneficial for future FDM applications in the field of immediate release tablets especially with respect to thermo-sensitive drugs.