Topical formulation for a JAK inhibitor
This invention relates to pharmaceutical formulations for topical skin application comprising (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, and use in the treatment of skin disorders.
1. A method of treating a skin disorder in a human patient in need thereof, comprising: applying to the patient's skin a pharmaceutically acceptable composition comprising: an oil-in-water emulsion, comprising: water, an oil component, an emulsifier component, a solvent component, and from about 0.5% to about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt, wherein the oil-in-water emulsion in the composition is a solubilized cream and further wherein the oil-in-water emulsion has a pH of not greater than 3.6; wherein treating is one or more of inhibiting the skin disorder and ameliorating the skin disorder; and wherein the skin disorder is an autoimmune skin disorder.
2. The method of claim 1 , wherein the applying step comprises application up to 84 consecutive days.
3. The method of claim 1 , wherein the autoimmune skin disorder is psoriasis or atopic dermatitis.
4. The method of claim 1 , wherein the water is present in an amount ranging from about 40% to about 60% by weight of the composition, and the oil component is present in an amount ranging from about 17% to about 27%.
5. The method of claim 4 , wherein the composition further comprises a stabilizing agent component.
6. The method of claim 1 , wherein about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt is present.
7. The method of claim 1 , wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
8. The method of claim 7 , wherein about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt is present.
9. A method of inhibiting JAK1 and/or JAK2 in a human patient suffering from a skin disorder, comprising:
applying to the patient's skin a pharmaceutically acceptable composition comprising:
an oil-in-water emulsion, comprising:
water,
an oil component,
an emulsifier component,
a solvent component, and
from about 0.5% to about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt,
wherein the oil-in-water emulsion in the composition is a solubilized cream and further wherein the oil-in-water emulsion has a pH of not greater than 3.6.
10. The method of claim 9 , wherein the applying step comprises application up to 84 consecutive days.
11. The method of claim 9 , wherein the skin disorder is an autoimmune skin disorder.
12. The method of claim 11 , wherein the skin disorder is atopic dermatitis.
13. The method of claim 9 , wherein the water is present in an amount ranging from about 40% to about 60% by weight of the composition, and the oil component is present in an amount ranging from about 17% to about 27% by weight of the composition.
14. The method of claim 13 , wherein the composition further comprises a stabilizing agent component.
15. The method of claim 9 , wherein about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt is present.
16. The method of claim 9 , wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
17. The method of claim 16 , wherein about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt is present.
18. A method of treating atopic dermatitis in a human patient, comprising:
applying to the patient's skin a pharmaceutically acceptable composition comprising:
an oil-in-water emulsion, comprising:
water,
an oil component,
an emulsifier component,
a solvent component, and
from about 0.5% to about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt,
wherein the oil-in-water emulsion in the composition is a solubilized cream and further wherein the oil-in-water emulsion has a pH of not greater than 3.6; and
wherein treating is one or more of inhibiting atopic dermatitis and ameliorating atopic dermatitis.
19. The method of claim 18 , wherein the applying step comprises application up to 84 consecutive days.
20. The method of claim 18 , wherein the water is present in an amount ranging from about 40% to about 60% by weight of the composition, and the oil component is present in an amount ranging from about 17% to about 27%.
21. The method of claim 20 , wherein the composition further comprises a stabilizing agent component.
22. The method of claim 18 , wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
23. The method of claim 18 , wherein treating is ameliorating atopic dermatitis.
24. A method of treating atopic dermatitis in a human patient, comprising:
applying to the patient's skin a pharmaceutically acceptable composition comprising:
an oil-in-water emulsion, comprising:
water,
an oil component,
an emulsifier component,
a solvent component, and
about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt,
wherein the oil-in-water emulsion in the composition is a solubilized cream and further wherein the oil-in-water emulsion has a pH of not greater than 3.6; and
wherein treating is one or more of inhibiting atopic dermatitis and ameliorating atopic dermatitis.
25. The method of claim 24 , wherein the applying step comprises application up to 84 consecutive days.
26. The method of claim 24 , wherein the water is present in an amount ranging from about 40% to about 60% by weight of the composition, and the oil component is present in an amount ranging from about 17% to about 27%.
27. The method of claim 26 , wherein the composition further comprises a stabilizing agent component.
28. The method of claim 24 , wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
29. The method of claim 24 , wherein treating is ameliorating atopic dermatitis.