Development of controlled release oral dosages by density gradient modification via three-dimensional (3D) printing and hot-melt extrusion (HME) technology

Abstract

Over the years, rapid development in 3D printed dosages has attracted the attention of pharmaceutical researchers due to the promising potential to revolutionize the way medicine is manufactured and distributed. The primary objective of this investigation was to combine fused deposition modeling (FDM) 3D printing with HME technology to explore the effect of manufacturing tablets with different densities and designs. These tablets are designed with an outer shell and inner core. HME technology causes some crystalline drugs to change form into an amorphous solid dispersion (ASD) during the processes used. ASDs are commonly used for poorly water-soluble drugs to improve dissolution and bioavailability significantly. In this trial, ketoprofen was selected as the model drug, loaded at 30%, so as to investigate the impact of changes to the filling density on the drug's dissolution profile, both mathematically and experimentally. A differential scanning calorimetry (DSC), confirmed that the HME process successfully transformed the ketoprofen formulations from a crystalline to amorphous for both filaments and 3D printed tablets. Texture analysis (TA) was employed to investigate the mechanical properties of these filaments and how they would behave in the FDM 3D printing process. Studying in vitro dissolution indicated that the filling density has an influence on the drug's release profile. It was shown that a 20% infill of the shell and a 40% infill of the core caused the quickest release of the drug. Also, the Peppas-Sahlin model showed a good fitting (R2 = 0.99) for ketoprofen-loaded 3D-printed tablets and explained the dissolution mechanism. Overall, this work illustrated the impacts of changing a printed tablet's filling density as a strategy to control the drug release performance for 3D printed dosages and the possibility of HME coupling 3D printing technology to prepare ASDs.