3D Printing via Melt Extrusion Deposition Facilitates the Use of Extended-Release Profiles in Preclinical Research and Development

Abstract

Traditional methods for developing modified-release (MR) formulations involve numerous iterations and large quantities of drug substances, which pose considerable challenges in exploration settings. Given the growing necessity for modified-release (MR) formulations in the pharmaceutical industry, particularly during the preclinical research and development phase, modified-release strategies may serve as attractive alternatives to discontinuing clinical development and could mitigate the costs and time associated with identifying new drug candidates. This study specifically explores the application of melt extrusion deposition (MED) 3D printing technology as a rapid prototyping platform for creating extended-release (ER) oral dosage forms tailored for the preclinical phase. Using the model compound BI 894416, the study demonstrated that MED 3D printing enables precise control over drug release profiles through both structural and compositional designs. The physicochemical analysis conducted during the 3D printing process revealed no degradation or compatibility issues. In vivo pharmacokinetic (PK) studies in rats and dogs validated the extended-release (ER) performance of BI 894416, with t_max values of 2–4 h in rats and 5 h in dogs. The ER tablets achieved prolonged plasma exposure and reduced peak-to-trough fluctuations compared to those of immediate-release (IR) formulations (ER: 144 versus IR: 929 in dogs). A Level A in vitro–in vivo correlation (IVIVC) was established, demonstrating strong alignment between in vitro dissolution and in vivo absorption up to 4 h, with a minor lag time observed. These results further confirmed the likely absorption of BI 894416 in the upper gastrointestinal (GI) tract and the potentially ascending colon. These findings highlight the potential of MED 3D printing to streamline the development of MR formulations in preclinical settings, offering a flexible, efficient, and material-sparing alternative to conventional approaches.