文摘
We found four new polymorphic forms (纬-, 蓻-, 味-, and 畏-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (伪-, 尾-, and 未-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the 蓻- and 畏-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the 蓻- and 畏-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The 伪-form was the most insoluble in 2-propanol at 35 掳C, and was thus concluded to be the most stable form. The 蓻-form was the most soluble, and a polymorphic transition from the 蓻- to the 伪-form was observed during solubility testing.
