Solid form of pyrazolopyridine compound
A novel crystalline form or amorphous of formula (I) and preparation method thereof are disclosed in present invention, wherein the novel crystalline form is substantially pure crystalline form I, form II, form III or form IV. The novel crystalline forms disclosed herein have good solubility, low hydroscopicity and good stability at high temperature (60° C.), high humidity (RH is 90%±5%) and/or under light (4500+/−500 Lux), which benefit for storage, meet the requirements of drug stability and therefore, making formula (I) suitable for formulation preparation and with high bioavailability.
1. A crystalline form of compound of formula (I), wherein the crystalline form is form III or form IV
wherein form III has an X-ray powder diffraction pattern comprising peaks at 6.68±0.2, 9.02±0.2, 25.44±0.2, 13.88±0.2, 17.23±0.2, 15.14±0.2 degrees in term of two theta; and wherein the peak at 25.44±0.2 degree is the strongest peak in the XRPD of form III, and wherein form IV has an X-ray powder diffraction pattern comprising peaks at 20.01±0.2, 27.03±0.2, 8.21±0.2, 18.15±0.2 and 27.38±0.2 degrees in term of two theta, and wherein the peak at 20.01±0.2 degree is the strongest peak in the XRPD of form IV.
2. The crystalline form of claim 1 , wherein the crystalline form is form III comprising peaks at 25.44±0.2, 13.88±0.2, 17.23±0.2, 15.14±0.2, 22.75±0.2, 12.60±0.2, 11.17±0.2, 9.02±0.2, 17.66±0.2, 22.52±0.2, 24.94±0.2, 17.53±0.2 and 6.68±0.2 degrees in term of two theta.
3. The crystalline form of claim 1 , wherein the crystalline form is form IV comprising peaks at 20.01±0.2, 27.03±0.2, 8.21±0.2, 18.15±0.2, 27.38±0.2, 19.22±0.2, 26.34±0.2, 29.38±0.2, 8.57±0.2, 14.45±0.2 and 7.15±0.2 degrees in term of two theta.
4. A process for preparing the crystalline form of claim 1 , comprising: dissolving any solid forms of the compound of formula (I) in a good solvent to form a solution; forming crystals by reducing the temperature of the solution or removing proportion of the solvent or adding an anti-solvent to the solution; and collecting the crystal.
5. The process of claim 4 , wherein the temperature of the solution is reduced to from about −10° C. to about 40° C.
6. The process of claim 4 , wherein the crystal is formed at room temperature.
7. The process of claim 4 , wherein the method of removing proportion of the solvent comprising distillation or evaporation or any combine thereof.
8. The process of any one claim 4 , wherein the amount of the removed solvent is about 20% to about 90% with respect to the total volume of the solution.
9. The process of any one claim 4 , wherein the amount of the removed solvent is about 30% with respect to the total volume of the solution.
10. A process for preparing the crystalline form of claim 1 , comprising dissolving the compound of formula (I) in a good solvent at room temperature to form a solution, and forming crystals by adding the solution to an anti-solvent or adding an anti-solvent to the solution.
11. The process of claim 4 , wherein the good solvent or anti-solvent is selected from one or more of NMP, DMF, water, methanol, ethanol, ethylene glycol, isopropanol, n-propanol, n-butanol, tert-butanol, THF, methylene chloride, DMSO, ethyl acetate, isopropyl acetate, butanone, acetone, acetonitrile and 1,4-dioxane.
12. The process of claim 11 , wherein the process for preparing the crystalline form III of the compound of formula (I), comprises:
mixing the compound of formula (I) with 1,4-dioxane,
heating the resulting mixture to reflux and stirring the mixture until the solid is completely dissolved to form a solution,
slowly cooling the solution to room temperature, and
stirring the solution for about 1 h to 300 h and collecting the crystals.
13. The process of claim 11 , wherein the crystalline form IV of the compound of formula (I) is formed, and wherein the good solvent is butanone.
14. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of claim 1 and one or more pharmaceutically acceptable carriers or excipients.
15. The process of claim 10 , wherein the good solvent or anti-solvent is selected from one or more of NMP, DMF, water, methanol, ethanol, ethylene glycol, isopropanol, n-propanol, n-butanol, tert-butanol, THF, methylene chloride, DMSO, ethyl acetate, isopropyl acetate, butanone, acetone, acetonitrile and 1,4-dioxane.
16. A method of treating cardiovascular diseases, thromboembolic diseases, ischemia, hypertension or treating sexual dysfunction in a patient by administering to the patient with the crystalline form of claim 1 .
17. A method of treating cardiovascular diseases, thromboembolic diseases, ischemia, hypertension or treating sexual dysfunction in a patient by administering to the patient with the pharmaceutical composition of claim 14 .