Purpose: The main purpose of this project was to use 3D printing coupled with HME technology to manufacture tablets with different drug release profiles , and to solve issues such as dose due to individual differences in administration/metabolism. This work also studied the relationship between drug release with 3D structure and polymer matrices .
Methods: As a test, 30% Acetaminophen (APAP), an anti-inflammatory analgesic and antipyretic, was mixed with 50% (w/w) hydroxypropyl methylcellulose (HPMC) and 20% (w/w) Soluplus®. Filaments were prepared using a ThermoFisher Scientific Process 11 twin-screw co-rotating extruder and an on-line NIR probe inserted at a 2 mm die as a process analysis technique (PAT) tool. A customized fuse-deposition model (FDM) based 3D printer was used to produce structured tablets. Tablets were designed to have a gradually decreasing internal density gradient. The tablets were printed with shells of various densities, (40%, 50%, and 60% fill density) and cores (60%, 80%, and 100% fill density) and combined in a variety of ways (Figure 1). DSC and TGA analyses were performed to investigate the crystallinity of the drug and determine the thermal stability of APAP/polymer. Cross-sectional images of 3D printed tablets were taken by scanning electron microscopy (SEM). Hardness tests and tablet geometry studies were also performed. In vitro drug release studies were conducted using a modified USP-II dissolution/osmotic device with simulated intestinal fluidTS (US Pharmacopeia, pH 6.8) .
Results: Filaments with stable drug loading were successfully produced, which can be confirmed by online near-infrared monitoring data. Filament characterization studies indicated that the drug-carrying filaments have sufficient physical and chemical properties. The filaments were successfully printed into the designed dosage forms. SEM photographs show porous shells and solid core structures (Figure 2).
Conclusion: The successful combination of 3D printing and HME created different tablet dosage forms that were more flexible than traditional methods and will most likely have wider applications in the future. This work also showcases the promising future of pharmaceutical 3D printing technology for personalized and patient-centric doses. These results may shift the paradigm of large-scale industrial-scale production to the selection of personalized precision pharmaceuticals.
Jiaxiang Zhang– Student, University of Mississippi, Oxford
Pengchong Xu– Research Assistant, University of Mississippi
Fengyuan Yang– Senior Staff Scientist, Ashland Specialty Ingredients
Thomas Dürig– Senior Director, Ashland Specialty Ingredients, Wilmington, Delaware
Michael Repka– Professor, University of Mississippi, Mississippi