Polymorphic form of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide and uses thereof
Disclosed herein, in certain embodiments, is a crystalline polymorph form A of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide. Further disclosed herein, in certain embodiments, are pharmaceutical compositions comprising the crystalline polymorph form A of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide.
1. A crystalline polymorph of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide having at least one of the following properties:
(a) a powder x-ray diffraction pattern substantially the same as the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph
(b) a differential scanning calorimetry pattern substantially the same as the a differential scanning calorimetry pattern shown in FIG. 2 for said crystalline polymorph
or
(c) a melting point onset as determined by differential scanning calorimetry at about 143° C. for said crystalline polymorph.
2. A polymorphic form of N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide made by a method comprising crystallizing amorphous N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide from a mixture of ethyl acetate and heptane to obtain said crystalline polymorph.
3. The polymorphic form of claim 2 , wherein the mixture of ethyl acetate and heptane is in a ratio of about 1-4 parts ethyl acetate to about 2-10 parts heptane.
4. The polymorphic form of claim 2 , wherein the mixture of ethyl acetate and heptane is in a ratio of about 2 parts ethyl acetate to about 5 parts heptane.
5. A composition comprising a pharmaceutically acceptable carrier and a crystalline polymorph having at least three of the following properties:
(a) a powder x-ray diffraction pattern substantially the same as the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph
(b) a differential scanning calorimetry pattern substantially the same as the a differential scanning calorimetry pattern shown in FIG. 2 for said crystalline polymorph
and
(c) a melting point onset as determined by differential scanning calorimetry at about 143° C. for said crystalline polymorph.
6. A composition comprising a pharmaceutically acceptable carrier and a crystalline polymorph of N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide made by a method comprising crystallizing amorphous N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide from a mixture of ethyl acetate and heptane to obtain said crystalline polymorph.
7. A crystalline polymorph of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide having at least one of the following properties:
(a) a powder x-ray diffraction pattern corresponding to the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph
(b) a differential scanning calorimetry pattern corresponding to the differential scanning calorimetry pattern shown in FIG. 2 for said crystalline polymorph
or
(c) a melting point onset as determined by differential scanning calorimetry at about 143° C. for said crystalline polymorph.
8. A crystalline polymorph of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide according to claim 7 having at least two of the following properties:
(a) a powder x-ray diffraction pattern corresponding to the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph
(b) a differential scanning calorimetry pattern corresponding to the differential scanning calorimetry pattern shown in FIG. 2 for said crystalline polymorph
or
(c) a melting point onset as determined by differential scanning calorimetry at about 143° C. for said crystalline polymorph.
9. A crystalline polymorph of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide according to claim 7 having the following properties:
(a) a powder x-ray diffraction pattern corresponding to the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph
(b) a differential scanning calorimetry pattern corresponding to the differential scanning calorimetry pattern shown in FIG. 2 for said crystalline polymorph
and
(c) a melting point onset as determined by differential scanning calorimetry at about 143° C. for said crystalline polymorph.
10. A crystalline polymorph of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide having a powder x-ray diffraction pattern corresponding to the powder x-ray diffraction pattern shown in FIG. 1 for said crystalline polymorph.