Abstract
Tofacitinib citrate (TOC) is clinically used primarily for the treatment of moderate to severe rheumatoid arthritis in patients who are intolerant or inadequately responsive to methotrexate. In this study, a new polymorph of TOC (form II) was prepared using solvent crystallization. The currently marketed form I and the self-prepared form II were characterized by XRD, DSC, FT-IR, and SEM, confirming that form II is a new polymorphic form of TOC. This new polymorph was then used in the development of TOC sustained-release tablets. In the formulation design, mannitol with low hygroscopicity was used to replace sorbitol. By adding a certain amount of microcrystalline cellulose to the tablet core and maintaining the mannitol content between 60 ~ 70% of the total core weight, an in vitro dissolution behavior similar to that of the reference formulation (f2 > 50) was achieved. This indicates that replacing sorbitol with mannitol as the osmotic agent in the osmotic pump tablet core is a practical and effective method. Additionally, key preparation processes for the TOC sustained-release tablets were investigated. The results suggest that the coating weight gain of the self-prepared sustained-release tablets should be controlled between 6% and 7%, and the suitable range for laser-drilled orifice diameter is 0.55 ~ 0.90 mm.