(W1130-04-24) Evaluation of Polymers for Extended-Release Formulations: Hot-Melt Extrusion Paired Fused Deposition Modeling 3D Printing

Purpose: To evaluate the printability of polymers for development of an extended-release formulation using Hot-melt extrusion paired with fused deposition modeling (FDM) 3D printing.

Methods: The present study investigates the printability of various polymers to develop extended-release formulations. Different polymers such as Kollidon® SR, Kollicoat® IR, Kollidon® 12 PF, and Kollidon® VA 64 were screened for their printability with FDM 3D printing employing the model drug acetaminophen (APAP). The physical mixtures were prepared in drug to polymer/polymeric mix at 30:70 ratios, and extrusion was carried out using a co-rotating twin-screw extruder (Process 11, ThermoFisher Scientific, Karlsruhe, Germany). DSC was utilized for characterization of filaments for the nature of APAP and potential degradation. The tablets were printed with the obtained filaments using a 3D printer (Prusa i3 3D desktop printer, Prusa Research, Prague, Czech Republic). Dissolution was performed for the 3D printed tablets in simulated gastric fluid (without enzyme) using a USP type II apparatus (SR8-plus, Hanson, Chatsworth, California, USA). Samples were collected at regular intervals and analyzed using a UV-Visible spectrophotometer. The impact of 3D printed tablet infill density on drug release was evaluated.

Results: Extrusion was successfully performed without a significant rise in torque values. The filaments obtained with drug and polymer alone were brittle in nature. Therefore, a polymeric mixture was used to produce the flexible filaments. Kollidon® SR was used as a common polymer in all the developed formulations along with other polymers. The drug-polymeric combinations except drug-Kollidon® SR-Kollicoat® IR combination produced brittle filaments, which were unsuitable for 3D printing. Thus, the Kollidon® SR-Kollicoat® IR polymeric mixture imparted flexibility to the filaments with improved 3D printability and is used in this study further. From the DSC data, no melting peak was observed in the thermograms of formulations, confirming the drug's transformation into an amorphous form during extrusion. These filaments were processed through a 3D printer to produce the tablets with different infill percentages. Round-shaped tablets were printed with 100%, 75%, and 50% infill densities at 180°C, and a honeycomb pattern was utilized. Dissolution testing was performed for the tablets in simulated gastric fluid (without enzyme) for 3 h and is represented in Figure 1(n=3). The F2 formulation with 50% infill met the USP desired drug release profile for the extended-release formulation of acetaminophen. It was observed that the percentage of Kollidon® SR and infill percentage showed an impact on drug release characteristics.

Conclusion: In this study, Kollicoat® IR imparted enough flexibility to the filaments for 3D printing. However, the Kollidon® SR concentration in the formulation impacted drug release profiles, and a decrease in infill percentage increases the drug release from the tablets. Thus, the selection of an appropriate polymer, its concentration, and tablet infill density is desired to achieve the anticipated drug release profiles in a 3D printed formulation. Further studies are ongoing regarding Kollidon® 12 PF and Kollidon® VA 64.

References: 1. Azad MA, Olawuni D, Kimbell G, Badruddoza AZM, Hossain MS, Sultana T. Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective. Pharmaceutics [Internet]. 2020;12:124. Available from: https://www.mdpi.com/1999-4923/12/2/124
2. Wang H, Dumpa N, Bandari S, Durig T, Repka MA. Fabrication of Taste-Masked Donut-Shaped Tablets Via Fused Filament Fabrication 3D Printing Paired with Hot-Melt Extrusion Techniques. AAPS PharmSciTech [Internet]. 2020;21:243. Available from: https://link.springer.com/10.1208/s12249-020-01783-0

Table 1. Formulation composition of 3D printed tablets



Figure 1. Dissolution profile of APAP 3D printed tablets