(42b) Additive Manufacturing of High Drug Loaded Extended Release Tablets via FDM 3D Printing

3D printing technology is an active research area in personalized medicine. Coupling of fused deposition modeling (FDM) based three-dimensional (3D) printing with hot melt extrusion (HME) has the distinct advantages of tailoring dosage forms, enhanced bioavailability of poorly water soluble drug as well as complex dosage geometries. However, there remain major challenges in forming 3D compatible filaments, due to the limitations such as low drug loading, challenges in developing required formulations suitable for HME along with inherent process limitations such as the need for high temperatures, limited options for pharmaceutically compatible polymers, inadequate filament mechanical properties such as brittleness, and achieving very good drug product content uniformity (CU). This work explores the ability to fabricate filaments that are compatible for FDM-3D printing with a wide range of drug loadings while retaining proper mechanical properties and good drug CU within the filaments. Griseofulvin (GF) and hydroxypropyl cellulose (HPC) was used as the model BCS Class II drug and the polymeric matrix, respectively. Dry GF and HPC powders were pre-mixed having up to 40 wt.% GF and dispersed into the molten polymeric matrix via HME. The produced filaments were used to produce cylindrical shape tablets in FDM 3D printing. All printed tablets showed good CU and sufficient mechanical properties up to 25 wt.% GF while high drug-loaded filaments i.e., 40 wt.% GF created processing difficulties in a 11 mm twin-screw extruder (TSE). TSE processing was successfully done for four different drug loads (5, 10, 15, and 25%) to examine their influence on mechanical properties as well as drug release. Increasing drug load from 5 to 25 wt.% in extruded filaments resulted in enhanced modulus of elasticity from 235.89 to 298.15 MPa, respectively. Using a FDM-3D printer, mini tablets were printed containing up to 25wt.% GF (15 mg). The printed tablets showed improved CU (RSD <2%), and acceptance values (AVs) for all printed tablets were less than 8. Drug loading in both filaments and 3D printed tablets showed similar values, indicating no degradation during extrusion, matching with DSC/TGA results. In vitro drug release testing for all 3D printed tablets revealed extended release without any burst effects for up to 12h. In summary, the filaments produced via HME provided high flexible dosing capability as well as required mechanical properties and could be used to prepare FDM 3D printed tablets that can be potentially used for personalized medicine.