Preparation of tofacitinib sustained-release tablets using hot melt extrusion technology

Abstract

This study aimed to develop a tablet that shows a drug release profile similar to the tofacitinib sustained-release tablet (Xeljanz XR®; OROS™) using hot melt extrusion technology. Tofacitinib citrate was selected as the drug. HPMCAS, HPMCP, and Kollidon VA64 were used as thermoplastic polymers to prepare a hot-melt extrudate. The extrudate was obtained from a twin screw extruder and pelletizer. The granules were compressed using a single punch press machine and then coated. TGA, DSC, XRD, FT-IR, and SEM were performed on the hot melt extrudate to understand its physicochemical properties. Dissolution tests were performed using the paddle method (USP Apparatus II). The results showed that the crystallinity state of tofacitinib changed to amorphous after the hot melt extrusion process; however, no chemical change was observed. The drug release profile was similar to that of Xeljanz XR®, which has an initial lag time owing to its OROS™ formulation; a coating process was performed to obtain a similar drug release profile. The lag time was controlled by adjusting the thickness of the coating layer. Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR^®.

Graphical Abstract

Keywords:

• Hot melt extrusion
• Tofacitinib
• sustained-release tablet
• Xeljanz XR^®

Author contributions

Conceptualization, S.-Y.K. and K.-Y. W., methodology. S.-Y.K. and I.P. investigation. S.-Y.K. and J.-B.P., writing—original draft preparation, S.-Y.K., writing—review and editing, I.P., K.-Y. W., and J.-B.P., supervision. K.-Y. W., J.-B.P. funding acquisition, J.-B.P., All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) [NRF-2019R1F1A1056572 and NRF-2022R1F1A1063127].