Compositions and methods for treating myelofibrosis
Provided herein are compositions and methods for treating myelofibrosis in a subject. The methods comprise administering to the subject an effective amount of compound which is which is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide or a pharmaceutical salt thereof or a hydrate thereof.
1. A capsule comprising a formulation comprising (i) a compound that is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate, (ii) a microcrystalline cellulose, and (iii) sodium stearyl fumarate,
wherein:
the weight ratio of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:9, and
sodium stearyl fumarate is about 1% by weight of the formulation.
2. The capsule unit of claim 1 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
3. The capsule of claim 1 , wherein the to formulation comprises about 117 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
4. The capsule of claim 1 , wherein the formulation comprises about 235 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate, about 357 mg of silicified microcrystalline cellulose, and about 6 mg of sodium stearyl fumarate.
5. The capsule of claim 1 , wherein the capsule is a hard gelatin capsule.
6. A method of treating myelofibrosis in a subject comprising administering a capsule comprising a formulation comprising (i) a compound that is N-tert-butyl-3-[(5-methyl-2-{[4(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate, (ii) a microcrystalline cellulose, and (iii) sodium stearyl fumarate,
wherein:
the weight ratio of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:9, and
sodium stearyl fumarate is about 1% by weight of the formulation.
7. A method of preparing a capsule comprising a formulation, wherein the method comprises blending a microcrystalline cellulose and sodium stearyl fumarate with a compound that is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate,
wherein:
the weight ratio of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:9, and
sodium stearyl fumarate is about 1% by weight of the formulation.
8. An article of manufacture comprising:
(a) a capsule comprising a formulation comprising (i) a compound that is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate, (ii) a microcrystalline cellulose, and (iii) sodium stearyl fumarate,
wherein:
the weight ratio of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:9, and
sodium stearyl fumarate is about 1% by weight of the formulation; and
(b) a package insert or a label indicating that the formulation is useful for treating myelofibrosis in a subject.
9. The capsule or claim 3 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
10. The article of manufacture of claim 8 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
11. The method of claim 7 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
12. The capsule of claim 1 , wherein the weight ratio or N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:2.
13. The capsule of claim 12 , wherein the formulation comprises about 117 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
14. The capsule of claim 12 , wherein the formulation comprises about 235 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
15. The capsule of claim 12 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
16. The capsule of claim 15 , wherein the formulation comprises about 117 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
17. The capsule of claim 15 , wherein the formulation comprises about 235 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
18. The capsule of claim 4 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
19. The article of manufacture of claim 8 , wherein the formulation comprises about 117 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
20. The article of manufacture of claim 19 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
21. The article of manufacture of claim 8 , wherein the weight ratio of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide to microcrystalline cellulose in the formulation is about 1:1.5 to about 1:2.
22. The article of manufacture of claim 21 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
23. The article or manufacture of claim 22 , wherein the formulation comprises about 117 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino)}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
24. The article of manufacture of claim 8 , wherein the formulation comprises about 235 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
25. The article of manufacture of claim 22 , wherein the formulation comprises about 235 mg of N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate.
26. The article of manufacture of claim 24 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.