Crystalline forms of tyrosine kinase inhibitors and their salts
The invention relates to various polymorphic forms and amorphous form of sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzate, including the polymorphic form A, mixtures of the polymorphs, process for the preparation thereof and the use thereof in a pharmaceutical composition containing thereof.
1. A method of treating a patient for a disease, disorder, or condition associated with NGF induced activation of a TrkA receptor, comprising:
administering to a patient in need of said treating, a crystalline polymorph Form A of Compound I, sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoate, with the following structure:
characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 10.0±0.3, 20.1±0.3, and 23.6±0.3,
wherein said disease, disorder or condition is selected from the group consisting of: psoriasis and inflammation.
2. The method of claim 1 , wherein the administered crystalline polymorph is further characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 14.5±0.3 and 18.1±0.3.
3. The method of claim 1 , wherein the administered crystalline polymorph is further characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 9.7±0.3 and 21.2±0.3.
4. The method of claim 1 , wherein the administered crystalline polymorph is further characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 14.5±0.3, 18.1±0.3, 9.7±0.3, and 21.2±0.3.
5. The method of claim 1 , wherein the administered crystalline polymorph exhibits an x-ray powder diffraction pattern that is substantially similar to that of FIG. 4 .
6. The method of claim 1 , wherein the administered crystalline polymorph exhibits a Raman spectrum that is substantially similar to that of FIG. 5 .
7. The method of claim 1 , wherein the administered crystalline polymorph exhibits a differential scanning calorimetry thermogram having an endotherm with an onset of about 244° C.
8. The method of claim 1 , wherein the administered crystalline polymorph exhibits a differential scanning calorimetry thermogram having an endothelia with a peak of about 250° C.
9. The method of claim 1 , wherein said disease, disorder, or condition is psoriasis.
10. A method of treating a patient for a disease, disorder, or condition associated with NGF induced activation of a TrkA receptor, comprising:
administering to a patient in need of said treating, a crystalline polymorph Form A of Compound I, sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoate, with the following structure:
characterized by having an x-ray powder diffraction pattern exhibiting three or more peak positions at degree two-theta selected from the group consisting of: 7.160, 8.757, 9.820, 10.161, 12.459, 14.641, 15.219, 17.680, 18.240, 19.104, 20.220, 21.381, 22.579, 23.721, 24.898, 25.761, 25.522, 27.161, 28.321, 29.481, 30.921, and 34.281,
wherein said disease, disorder or condition is selected from the group consisting of: psoriasis and inflammation.
11. The method of claim 10 , wherein the administered crystalline polymorph exhibits an x-ray powder diffraction pattern having five or more peak positions at degree two-theta selected from the group consisting of: 7.160, 8.757, 9.820, 10.161, 12.459, 14.641, 15.219, 17.680, 18.240, 19.104, 20.220, 21.381, 22.579, 23.721, 24.898, 25.761, 25.522, 27.161, 28.321, 29.481, 30.921, and 34.281.
12. The method of claim 10 , wherein the administered crystalline polymorph exhibits an x-ray powder diffraction pattern having seven or more peak positions at degree two-theta selected from the group consisting of: 7.160, 8.757, 9.820, 10.161, 12.459, 14.641, 15.219, 17.680, 18.240, 19.104, 20.220, 21.381, 22.579, 23.721, 24.898, 25.761, 25.522, 27.161, 28.321, 29.481, 30.921, and 34.281.
13. The method of claim 10 , wherein the administered crystalline polymorph exhibits an x-ray powder diffraction pattern having ten or more peak positions at degree two-theta selected from the group consisting of: 7.160, 8.757, 9.820, 10.161, 12.459, 14.641, 15.219, 17.680, 18.240, 19.104, 20.220, 21.381, 22.579, 23.721, 24.898, 25.761, 25.522, 27.161, 28.321, 29.481, 30.921, and 34.281.
14. The method of claim 10 , wherein the administered crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of: 7.160, 8.757, 9.820, 10.161, 12.459, 14.641, 15.219, 17.680, 18.240, 19.104, 20.220, 21.381, 22.579, 23.721, 24.898, 25.761, 25.522, 27.161, 28.321, 29.481, 30.921, and 34.281.
15. The method of claim 10 , wherein said disease, disorder, or condition is psoriasis.
16. A method of treating a patient for a disease, disorder, or condition associated with NGF induced activation of a TrkA receptor, comprising administering to a patient in need of said treating, a composition, comprising:
a) a crystalline polymorph Form A of Compound I, sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoate, with the following structure:
characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 10.0±0.3, 20.1±0.3, and 23.6±0.3;
or
b) a combination of said crystalline polymorph Form A of Compound I and an amorphous form of Compound I;
and
one or more pharmaceutically acceptable excipients,
wherein said disease, disorder or condition is selected from the group consisting of: psoriasis and inflammation.
17. The method of claim 16 , wherein said disease, disorder, or condition is psoriasis.
18. A method of treating a patient for a disease, disorder, or condition associated with NGF induced activation of a TrkA receptor, comprising administering to a patient in need of said treating a solid or semi-solid dosage form, comprising:
a) a crystalline polymorph Form A of Compound I, sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoate, with the following structure:
characterized by having x-ray powder diffraction pattern peak positions at degree two-theta of 10.0±0.3, 20.1±0.3, and 23.6±0.3;
or
b) a combination of said crystalline polymorph Form A of Compound I and an amorphous form of Compound I,
wherein said disease, disorder or condition is selected from the group consisting of: psoriasis and inflammation.
19. The method of claim 18 , wherein the administered solid or semi-solid dosage form comprises one or more of a tablet, hard capsule, soft capsule, powder, suppository, and gel.
20. The method of claim 18 , wherein the administered solid or semi-solid dosage form comprises one or more of an injectable form, a transdermal patch, a sprayable form, and an implantable depot.
21. The method of claim 18 , wherein said disease, disorder, or condition is psoriasis.
22. The method of claim 1 , wherein said patient is a human.
23. The method of claim 16 , wherein said patient is a human.
24. The method of claim 18 , wherein said patient is a human.
25. The method of claim 16 , wherein the composition is formulated for oral, transdermal, or transmucosal administration.
26. The method of claim 25 , wherein the composition for oral administration is in the form of a tablet, a lozenge, an aqueous suspension, an oily suspension, a capsule, granules, a powder, an emulsion, a syrup, or an elixir.
27. The method of claim 16 , further comprising administering an opioid receptor agonist.
28. The method of claim 1 , wherein said disease, disorder, or condition is inflammation.
29. The method of claim 10 , wherein said disease, disorder, or condition is inflammation.
30. The method of claim 16 , wherein said disease, disorder, or condition is inflammation.
31. The method of claim 18 , wherein said disease, disorder, or condition is inflammation.