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 pharmaceutical composition suitable for topical skin application, 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 for topical skin application and further wherein the oil-in-water emulsion has a pH of not greater than 3.6.
2. The composition of claim 1 , wherein said solubilized cream is suitable for application to the skin for up to 84 consecutive days.
3. The composition of claim 1 , further comprising a stabilizing agent component.
4. The composition 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% by weight of the composition.
5. The composition of claim 4 , further comprising a stabilizing agent component present in an amount of about 0.3% to about 0.5% by weight of the composition.
6. The composition of claim 1 , wherein about 0.5% 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 composition of claim 1 , wherein about 1.0% 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.
8. A pharmaceutical composition suitable for topical skin application, 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 for topical skin application and further wherein the oil-in-water emulsion has a pH of not greater than 3.6.
9. The composition of claim 1 , wherein about 0.5% to about 1.0% 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.
10. The composition of claim 1 , wherein said oil-in-water emulsion has a pH of not greater than 3.6 at 0 months at 25° C.
11. The composition of claim 1 , wherein said oil-in-water emulsion has a pH of not greater than 3.6 at 6 months at 25° C.
12. The composition of claim 1 , wherein said oil-in-water emulsion has a pH of not greater than 3.6 at 12 months at 25° C.
13. The composition of claim 1 , wherein said oil-in-water emulsion has a pH of not greater than 3.6 at 24 months at 25° C.
14. A pharmaceutical composition suitable for topical skin application 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 for topical skin application and further wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
15. The composition of claim 14 , wherein said solubilized cream is suitable for application to the skin for up to 84 consecutive days.
16. The composition of claim 14 , 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.
17. The composition of claim 14 , wherein about 0.5% 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. The composition of claim 14 , wherein about 1.0% 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.
19. A pharmaceutical composition suitable for topical skin application 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 for topical skin application and further wherein the oil-in-water emulsion has a pH of 2.9 to 3.6.
20. The composition of claim 14 , wherein about 0.5% to about 1.0% 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.