The present application belongs to the technical field of crystalline compounds, and particularly relates to a preparation method of small-particle-size tigositabine
crystal form A. The method comprises dissolving tigositabine crude product in an acidic mixed
solvent (pH 2-3) containing a surfactant, removing impurities by hot
filtration after constant-temperature stirring, transferring the filtrate into a crystallizer, pressurizing and cooling, slowly releasing pressure, adding an alkali solution to adjust to neutrality, and obtaining the product after low-temperature aging,
filtration and
drying. The present application effectively inhibits
crystal grain agglomeration and growth by means of synergistic methods such as surfactant regulation, controllable
nucleation by pressurizing and cooling, slow
pressure release and mild alkali adjustment
crystallization, and small-particle-size
crystal form A with a Dv(90) of 7.46-8.97 μm is prepared. The product yield reaches 85.5%-88.0%, the
dissolution rate in water is significantly better than that of the
original research and the product of the comparative example, and the
dissolution equilibrium can be basically reached in 30 min, thus solving the technical pain points of large crystal size and slow
dissolution in the prior art, and the present application can be widely used in the research and production of tigositabine preparations.