(W1130-03-18) Formulation Development of Famotidine Floating Tablets Using Hot-Melt Extrusion and 3D Printing Techniques

Purpose: It is well-known that the absorption of famotidine tablets taken orally is incomplete and dependent on the dose. The oral bioavailability usually ranges from 40% to 50%. One way to improve drug bioavailability is to use gastroretentive drug systems, such as floating tablets designed to float over the gastric area and remain in the stomach for extended periods. The main objective of this study is to develop famotidine floating tablets using a combination of hot melt extrusion (HME) and Fused Deposition Modeling (FDM) 3D printing technology. By amorphizing famotidine and dispersing it on a polymeric carrier, we aim to enhance its solubility and release. The 3D-printing design of the floating tablet is also expected to contribute to better drug delivery.

Methods: Various polymeric carriers, including hydroxypropyl Cellulose (Klucel ^TM HPC-LF) and (Klucel^TM HPC-EF), hydroxypropyl methylcellulose (HPMC- Methocel^TM E5), ethyl cellulose (Ethocel^TM EC) and polyethylene oxide (PEO N80) were used with 10% (w/w) famotidine. Polyethylene Glycol (PEG 1500) was added as a plasticizer. The resulting physical mixtures were extruded using an 11 mm twin-screw co-rotating extruder (process 11, Thermo Fisher Scientific, Waltham, MA, USA) at an extrusion temperature of 115-160 ° C and screw speed of 100 rpm. The filaments produced were then printed using an FDM-3D printer (Prusa i3 3D desktop printer, Prusa Research, Prague, Czech Republic) with a thickness of 0.4 mm, line pattern, and 100% infill density at a printing temperature of 180°C with a hollow shape as shown in Figure 1a, 1b, and 1c to achieve a low-density tablet that could float on the surface of the stomach for a longer period. Differential Scanning Calorimetry (DSC) was used to evaluate the physical state of famotidine, polymeric carriers, HME filaments, and 3D-printed tablets. A floating test was performed on all 3D printed tablets to investigate the impact of the 3D printing design on the floating behavior. Famotidine in vitro drug release test was evaluated using a United States Pharmacopeia (USP) dissolution apparatus II (paddle) (Hanson Research Virtual Instruments SR8 Plus, Los Angeles, CA). The dissolution medium was 900 mL 0.1 N HCL and was maintained at 37± 0.5 ºC and 50 rpm.

Results: Hot melt extrusion was successfully used to prepare famotidine HME filaments (Figure 2). Out of seventeen filaments, M10, M11, M15, M16, and M17 were successfully printed. The famotidine DSC thermograms (Figure 3) indicated an endothermic melting peak at 163.5°C. However, this peak disappeared in both the extruded filament and 3D-printed tablets. This disappearance suggests that famotidine was completely solubilized in the polymeric carrier. Furthermore, the floating test showed that 3D-printed tablets M10 and M11 floated for 9 hours while M17 floated for 8 hours. The in vitro release profile of the M10 3D printed tablet showed a prolonged drug release for up to 9 hours (Figure 1d).

Conclusion: The use of HME showed great promise in enhancing the solubility and developing filaments suitable for FDM-3D printing. It was concluded that the formulation compositions, printing design, and pattern are the keys to developing 3D-printed floating tablets for famotidine, which help famotidine to remain in the stomach for sustained oral drug delivery, ensuring optimal bioavailability.

References: D. M. Smith, Y. Kapoor, G. R. Klinzing, and A. T. Procopio, “Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule,” Int J Pharm, vol. 544, no. 1, pp. 21–30, Jun. 2018, doi: 10.1016/J.IJPHARM.2018.03.056.
V. K. Pawar, S. Kansal, G. Garg, R. Awasthi, D. Singodia, and G. T. Kulkarni, “Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems,” https://doi.org/10.3109/10717544.2010.520354, vol. 18, no. 2, pp. 97–110, Feb. 2010, doi: 10.3109/10717544.2010.520354


Figure 1. The floating tablet design (a: software cylinder design, b: 3D shape hollow cylinder
design with a bottom layer attached c: top layer d: floating test on M10 and M11 3D printed tablets)



Figure2.HME extruded famotidine filaments


Figure 3. DSC thermogram of(a) F10, 11, 13 for both filaments (F) and printed tablets (P), Famotidine, HPMC-E5, HPC-LF, EC. (b)F15, 16, 17 for filaments (F) and printed tablets (P), Famotidine, HPMC-E5, PEO N80.