Pre-prescription Study Based on Physical and Chemical Properties of Tofacitinib Citrate

OBJECTIVE To investigate the physical and chemical properties of tofacitinib citrate, to provide theoretical basis for its formulation, process design, packaging and storage, etc. METHODS HPLC was used to determine the equilibrium solubility, lipid-water partition coefficient(P) and wettability of the drug in different pH buffers and water. The influencing factor trials of the drug were tested. The particle size, particle size distribution, infrared spectroscopy(FTIR), X-ray diffraction(XRD), differential scanning calorimetry(DSC) and scanning electron microscope(SEM) of the drug were determined. RESULTS The equilibrium solubility of tofacitinib citrate was 0.183 4-22.594 1 mg·mL^-1 in pH 1.0-8.0 buffer and water, which was a highly soluble drug. Among them, the equilibrium solubility in pH 1.0 buffers was the largest. The lgP was -1.34-1.28 in the above medium, belongs to a low permeability drug. Among them, the lgP in pH 3.6 buffer was the largest. The contact angles in the above medium were all <90°, and they were all easily wetted by these media. Tofacitinib citrate was stable under high temperature, high humidity and strong light irradiation. The average particle size of tofacitinib citrate was (29.85±0.17)µm. XRD, DSC and SEM results all showed that tofacitinib citrate was a crystalline drug, the melting point was 210 ℃. FTIR results showed that tofacitinib citrate had strong infrared characteristic peaks at 3 375.44, 3 134.51, 1 732.54, 1 711.78, 1 625.24, 1 551.03, 1 529.52, 1 473.76, 1 448.28, 1 409.48, 1 348.17, 1 213.59, 1 170.22, 1 115.37, 1 077.68, 1 023.87, 916.97, 846.38, 775.66, 741.84, 703.42, 603.15, 444.07 cm^-1, etc. CONCLUSION Tofacitinib citrate is a BCS class III drug. It is suitable to be designed into a gastric retention type drug delivery system, which is beneficial to the dissolution and absorption of the drug in the upper digestive tract to improve the bioavailability. The tofacitinib citrate used in this experiment is a stable crystalline drug that can meet the requirements of general preparation production, packaging, and storage.