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 formulation for topical skin application, comprising:
an oil-in-water emulsion; and
a therapeutically effective amount of a therapeutic agent which is (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof
2 . A pharmaceutical formulation according to claim 1 , wherein the emulsion comprises water, an oil component, and an emulsifier component.
3 - 4 . (canceled)
5 . A pharmaceutical formulation according to claim 2 , wherein the oil component is present in an amount of about 20% to about 27% by weight of the formulation.
6 . (canceled)
7 . A pharmaceutical formulation according to claim 2 , wherein the oil component comprises one or more substances independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone.
8 . A pharmaceutical formulation according to claim 2 , wherein the oil component comprises an occlusive agent component.
9 . (canceled)
10 . A pharmaceutical formulation according to claim 8 , wherein the occlusive agent component is present in an amount of about 5% to about 10% by weight of the formulation.
11 . (canceled)
12 . A pharmaceutical formulation according to claim 8 , wherein the occlusive agent component comprises white petrolatum.
13 . A pharmaceutical formulation according to claim 2 , wherein the oil component comprises a stiffening agent component.
14 - 15 . (canceled)
16 . A pharmaceutical formulation according to claim 13 , wherein the stiffening agent component is present in an amount of about 4% to about 7% by weight of said formulation.
17 - 18 . (canceled)
19 . A pharmaceutical formulation according to claim 13 , wherein the stiffening agent component comprises one or more substances independently selected from C 16-18 fatty alcohols.
20 . (canceled)
21 . A pharmaceutical formulation according to claim 2 , wherein the oil component comprises an emollient component.
22 . (canceled)
23 . A pharmaceutical formulation according to claim 21 , wherein the emollient component is present in an amount of about 7% to about 13% by weight of the formulation.
24 - 25 . (canceled)
26 . A pharmaceutical formulation according to claim 21 , wherein the emollient component comprises one or more substances independently selected from light mineral oil, medium chain triglycerides, and dimethicone.
27 - 28 . (canceled)
29 . A pharmaceutical formulation according to claim 2 , wherein the water is present in an amount of about 45% to about 55% by weight of the formulation.
30 - 32 . (canceled)
33 . A pharmaceutical formulation according to claim 2 , wherein the emulsifier component is present in an amount of about 4% to about 7% by weight of the formulation.
34 . (canceled)
35 . A pharmaceutical formulation according to claim 2 , wherein the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters.
36 . (canceled)
37 . A pharmaceutical formulation according to claim 1 , wherein said pharmaceutical formulation further comprises a stabilizing agent component.
38 - 39 . (canceled)
40 . A pharmaceutical formulation according to claim 37 , wherein the stabilizing agent component is present in an amount of about 0.3 to about 0.5% by weight of the formulation.
41 . (canceled)
42 . A pharmaceutical formulation according to claim 37 , wherein the stabilizing agent component comprises xanthan gum.
43 . A pharmaceutical formulation according to claim 1 , wherein said pharmaceutical formulation further comprises a solvent component.
44 - 45 . (canceled)
46 . A pharmaceutical formulation according to claim 43 , wherein the solvent component is present in an amount of about 20% to about 25% by weight of the formulation.
47 . A pharmaceutical formulation according to claim 43 , wherein the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols.
48 . (canceled)
49 . A pharmaceutical formulation according to claim 1 , wherein the therapeutic agent is present in an amount of about 0.5% to about 1.5% by weight of the formulation on a free base basis.
50 . A pharmaceutical formulation according to claim 1 , wherein said therapeutic agent is present in an amount of about 0.5% by weight of the formulation on a free base basis.
51 . A pharmaceutical formulation according to claim 1 , wherein said therapeutic agent is present in an amount of about 1% by weight of the formulation on a free base basis.
52 . A pharmaceutical formulation according to claim 1 , wherein said therapeutic agent is present in an amount of about 1.5% by weight of the formulation on a free base basis.
53 . A pharmaceutical formulation according to claim 1 , wherein said therapeutic agent is (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile phosphoric acid salt.
54 . A pharmaceutical formulation according to claim 1 , comprising:
from about 35% to about 65% of water by weight of the formulation;
from about 10% to about 40% of an oil component by weight of the formulation;
from about 1% to about 9% of an emulsifier component by weight of the formulation;
from about 10% to about 35% of a solvent component by weight of the formulation;
from about 0.05% to about 5% of a stabilizing agent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
55 . A pharmaceutical formulation according to claim 1 , comprising:
from about 40% to about 60% of water by weight of the formulation;
from about 15% to about 30% of an oil component by weight of the formulation;
from about 2% to about 6% of an emulsifier component by weight of the formulation;
from about 15% to about 30% of a solvent component by weight of the formulation;
from about 0.1% to about 2% of a stabilizing agent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
56 . A pharmaceutical formulation according to claim 1 , comprising:
from about 45% to about 55% of water by weight of the formulation;
from about 17% to about 27% of an oil component by weight of the formulation;
from about 3% to about 5% of an emulsifier component by weight of the formulation;
from about 20% to about 25% of a solvent component by weight of the formulation;
from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
57 . A pharmaceutical formulation according to claim 1 , comprising:
from about 45% to about 55% of water by weight of the formulation;
from about 17% to about 27% of an oil component by weight of the formulation;
from about 4% to about 7% of an emulsifier component by weight of the formulation;
from about 20% to about 25% of a solvent component by weight of the formulation;
from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
58 . A pharmaceutical formulation according to claim 54 , wherein:
the oil component comprises one or more substances independently selected from petrolatums, fatty alcohols, mineral oils, triglycerides, and dimethicones;
the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters;
the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols; and
the stabilizing agent component comprises one or more substances independently selected from polysaccharides.
59 . A pharmaceutical formulation according to claim 54 , wherein:
the oil component comprises one or more substances independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone;
the emulsifier component comprises one or more substances independently selected from glyceryl stearate and polysorbate 20;
the solvent component comprises one or more substances independently selected from propylene glycol and polyethylene glycol; and
the stabilizing agent component comprises xanthan gum.
60 . A pharmaceutical formulation according to claim 1 , comprising:
from about 35% to about 65% of water by weight of the formulation;
from about 2% to about 15% of an occlusive agent component by weight of the formulation;
from about 2% to about 8% of a stiffening agent component by weight of said formulation;
from about 5% to about 15% of an emollient component by weight of the formulation;
from about 1% to about 9% of an emulsifier component by weight of the formulation;
from about 0.05% to about 5% of a stabilizing agent component by weight of the formulation;
from about 10% to about 35% of a solvent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
61 . A pharmaceutical formulation according to claim 1 , comprising:
from about 40% to about 60% of water by weight of the formulation;
from about 5% to about 10% of an occlusive agent component by weight of the formulation;
from about 2% to about 8% of a stiffening agent component by weight of said formulation;
from about 7% to about 12% of an emollient component by weight of the formulation;
from about 2% to about 6% of an emulsifier component by weight of the formulation;
from about 0.1% to about 2% of a stabilizing agent by weight of the formulation;
from about 15% to about 30% of a solvent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
62 . A pharmaceutical formulation according to claim 1 , comprising:
from about 45% to about 55% of water by weight of the formulation;
from about 5% to about 10% of an occlusive agent component by weight of the formulation;
from about 3% to about 6% of a stiffening agent component by weight of said formulation;
from about 7% to about 13% of an emollient component by weight of the formulation;
from about 3% to about 5% of an emulsifier component by weight of the formulation;
from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation;
from about 20% to about 25% of a solvent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
63 . A pharmaceutical formulation according to claim 1 , comprising:
from about 45% to about 55% of water by weight of the formulation;
from about 5% to about 10% of an occlusive agent component by weight of the formulation;
from about 4% to about 7% of a stiffening agent component by weight of said formulation;
from about 7% to about 13% of an emollient component by weight of the formulation;
from about 4% to about 7% of an emulsifier component by weight of the formulation;
from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation;
from about 20% to about 25% of a solvent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
64 . A pharmaceutical formulation according to claim 1 , comprising:
from about 45% to about 55% of water by weight of the formulation;
about 7% of an occlusive agent component by weight of the formulation;
from about 4.5% to about 5% of a stiffening agent component by weight of said formulation;
about 10% of an emollient component by weight of the formulation;
from about 4% to about 4.5% of an emulsifier component by weight of the formulation;
about 0.4% of a stabilizing agent component by weight of the formulation;
about 22% of a solvent component by weight of the formulation; and
from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.
65 . A pharmaceutical formulation according to claim 60 , wherein the combined amount of the stiffening agent component and the emulsifier component is at least about 8% by weight of the formulation.
66 . A pharmaceutical formulation according to claim 60 , wherein:
the occlusive agent component comprises a petrolatum;
the stiffening agent component comprises one or more substances independently selected from one or more fatty alcohols;
the emollient component comprises one or more substances independently selected from mineral oils and triglycerides;
the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters;
the stabilizing agent component comprises one or more substances independently selected from polysaccharides; and
the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols.
67 . A pharmaceutical formulation according to claim 60 , wherein:
the occlusive agent component comprises white petrolatum;
the stiffening agent component comprises one or more substances independently selected from cetyl alcohol and stearyl alcohol;
the emollient component comprises one or more substances independently selected from light mineral oil, medium chain triglycerides, and dimethicone;
the emulsifier component comprises one or more substances independently selected from glyceryl stearate and polysorbate 20;
the stabilizing agent component comprises xanthan gum; and
the solvent component comprises one or more substances independently selected from propylene glycol and polyethylene glycol.
68 - 74 . (canceled)
75 . A method of treating a skin disorder in a patient in need thereof, comprising applying a pharmaceutical formulation according to claim 1 to an area of skin of said patient.
76 . The method of claim 75 , wherein the skin disorder is a topic dermatitis or psoriasis.
77 . The method of claim 75 , wherein the skin disorder is psoriasis.
78 . The method of claim 75 , wherein said skin disorder is skin sensitization, skin irritation, skin rash, contact dermatitis or allergic contact sensitization.
79 . The method of claim 75 , wherein said skin disorder is a bullous skin disorder.
80 . The method of claim 79 , wherein said bullous skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP).
81 - 82 . (canceled)