<p>Tofacitinib citrate is a novel oral small molecule JAK3 inhibitor that is clinically utilized for the treatment of moderate to severe rheumatoid arthritis in patients who are intolerant or insufficiently responsive to methotrexate. As a treatment for chronic diseases, its osmotic pump-type oral sustained-release formulation has been implemented in clinical practice. This study aimed to evaluate its compatibility with 12 common excipients used in osmotic pump-type oral sustained-release formulations. Compatibility studies were conducted through the preparation of binary mixtures (1:1, w/w) of tofacitinib citrate with the selected excipients. The binary mixtures were analyzed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and isothermal stress testing (IST). The DSC results indicated that the mixture of maltodextrin and tofacitinib citrate exhibited a new absorption peak, whereas the mixtures of sorbitol and mannitol with tofacitinib citrate resulted in the disappearance of the characteristic absorption peak of tofacitinib citrate, indicating their incompatibility. The results from FTIR and IST further confirmed that maltodextrin is incompatible with tofacitinib citrate and should be avoided in formulation development. Conversely, sorbitol and mannitol were found to be compatible with tofacitinib citrate, as evidenced by the results from FTIR, XRD, and IST. The disappearance of the main peak of tofacitinib citrate in the mixtures was attributed to its dissolution in the molten excipients.</p>