Crystalline form of a benzimidazole derivative and a preparation method thereof
The present invention relates to a novel crystalline form of a benzimidazole derivative and a preparation method thereof. The novel crystalline form according to the present invention is hardly changed chemically and/or physically under a long-term photo-stressed condition, has a low hygroscopicity, and has an extremely low static-electricity-inducing capability, thus being advantageous for formulation, and due to the excellent stability of the crystal form itself, it is very useful for long-term storage of the compound.
1. A crystalline form A of a compound represented by the following Formula 1 having an X-ray powder diffraction pattern with peaks at diffraction angles of 8.1°, 10.0°, 12.6°, 14.9°, 15.6°, 16.5°, 17.2°, 19.6°, 23.1°, 24.2°, 28.1°, 30.2°, and 31.6° (2θ±0.2°):
2. The crystalline form A of claim 1 , wherein the crystalline form A has an endothermal peak at a temperature between 220° C. and 225° C. in differential scanning calorimetry.
3. The crystalline form A of claim 1 , wherein the crystalline form A has an IR spectrum with characteristic absorption peaks at 832 cm −1 , 1071 cm −1 , 1127 cm −1 , 1326 cm −1 , 1403 cm −1 , 1440 cm −1 , 1598 cm −1 , 2934 cm −1 , 3062 cm −1 , and 3124 cm −1 .
4. A method of preparing a crystalline form A of a compound represented by the following Formula 1, comprising:
suspending the compound represented by Formula 1 in any random form in a solvent selected from the group consisting of acetonitrile, C 1-4 alkylacetate, C 1-4 dichloroalkane, chloroform, tetrahydrofuran, toluene, di(C 1-4 alkyl)ether, (C 1-4 alkyl)(C 1-4 alkyl)ether, C 1-4 alkyl ether, water and a mixture thereof;
subjecting the resulting solution to heat-treatment while stirring for 1 hour to 24 hours; and
cooling the resulting solution to room temperature followed by ripening crystals while stirring for 1 hour to 48 hours:
5. The method of claim 4 , wherein the solvent is acetonitrile, methyl acetate, ethyl acetate, isopropyl acetate, 1,2-dichloroethane, methylene chloride, chloroform, tetrahydrofuran, toluene, diethyl ether, isopropyl ether, tert-butyl methyl ether, water or a mixture thereof.
6. The method of claim 4 , wherein the heat-treatment is to increase the temperature up to from 50° C. to 120° C.
7. A method of preparing a crystalline form A of a compound represented by the following Formula 1, comprising:
dissolving the compound represented by Formula 1 in any random form in a solvent selected from the group consisting of C 1-4 alcohol, acetone, and a mixture thereof;
crystallizing the compound by adding an antisolvent to the resulting solution; and
ripening the resulting crystal while stirring for 6 hours to 24 hours at room temperature:
8. The method of claim 7 , wherein the solvent is methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, t-butanol, acetone, or a mixture thereof.
9. The method of claim 7 , wherein the antisolvent is water, isopropyl ether, acetonitrile, diethyl ether, tert-butyl methyl ether, or a mixture thereof.
10. The method of claim 4 , further comprising filtering or drying.
11. The method of claim 7 , further comprising filtering or drying.