Pyrazole pharmaceutical composition
A pharmaceutical composition of pyrazole compound and a surfactant and a method of using the same to treat atopic dermatitis.
1 . A solid pharmaceutical composition comprising a) a pharmaceutically effective amount of the compound of Formula (I)
or salt or solvate thereof; and
b) a pharmaceutically acceptable carrier wherein the carrier comprises a surfactant which is an ester of tocopherol, polyethylene glycol (PEG) and a dicarboxylic acid.
2 . The pharmaceutical composition of claim 1 , wherein the tocopherol is alpha tocopherol, the molecular weight of the PEG is between 100 and 10, 000 Da and the dicarboxylic acid is of the formula HO2C—R—CO2H, where R is C2-C20 alkyl.
3 . The pharmaceutical composition of claim 1 , wherein the carrier comprises D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS).
4 . The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is present in a crystalline form.
5 . The pharmaceutical composition of claim 1 , wherein the amount of the compound of Formula (I) in the composition is between about 0.5 and about 10% or is between about 1.0 and about 5.0% or is about 2% (w/w).
6 . The pharmaceutical composition of claim 3 , wherein the amount of TPGS in the composition is between about 0.5 and about 10% or is between about 1.0 and about 5.0% or is between about 1.0% and about 2.5% (w/w).
7 . The pharmaceutical composition of claim 1 , further comprising one or more excipients selected from, a filler, a lubricant, a binder and a disintegrant.
8 . The pharmaceutical composition of claim 7 , wherein the filler is a microcrystalline cellulose, a lactose or mixtures thereof.
9 . The pharmaceutical composition of claim 7 , wherein the lubricant is magnesium stearate.
10 . The pharmaceutical composition of claim 7 , wherein the disintegrant is sodium starch glycolate.
11 . The pharmaceutical composition of claim 7 , wherein the binder is hydroxypropyl cellulose.
12 . A method of treating atopic dermatitis comprising administering to an animal in need thereof, an effective amount of the pharmaceutical composition of claim 1 .
13 . The method of claim 12 , wherein the effective amount of the compound of Formula (I) is between about 0.1 and about 2.0 mg/kg body weight.
14 . The method of claim 12 , wherein the animal is a dog.
15 . The method of claim 12 , wherein the composition is administered once per day or twice per day.
16 . The method of claim 12 , wherein the composition is administered with food.
17 . The method of claim 12 , wherein the composition is administered twice a day for 14 days and then once a day for 14 days.
18 . The method of claim 12 , wherein the composition is administered once a day for 28 days.
19 . A process to make the pharmaceutical composition of claim 3 comprising
i) forming a powder blend of the compound of Formula (I) with a filler and a disintegrant;
ii) spraying the dry powder with an aqueous TPGS solution and mixing to combine the solution with the powder;
iii) drying the product of step ii) to produce granules;
iv) size reducing the granules;
v) lubricating the product of step iv); and
vi) compressing the product of step v) into a tablet to produce the pharmaceutical composition.
20 . The process of claim 19 , wherein the forming of the powder blend of step i) or the mixing of step ii) are accomplished with a high shear granulator.
21 . A process to make the pharmaceutical composition of claim 3 comprising
i) Forming a powder blend of the compound of Formula (I) with filler and disintegrant and heating this powder blend;
ii) melting TPGS and combining it with the heated powder blend of step i);
iii) cooling the product of step ii) to produce granules; and
iv) size reducing the granules of step iii)
v) lubricating the product of step iv); and
vi) compressing the product of step v) into a tablet to produce the pharmaceutical composition.
22 . The process of claim 19 , wherein the compound of Formula (I) is further combined with a binder in step i).
23 . The process of claim 21 , wherein the compound of Formula (I) is further combined with a binder in step i).
24 . The pharmaceutical composition of claim 1 , wherein the dicarboxylic acid is succinic acid.
25 . A solid pharmaceutical composition comprising
a) 0.5-10% w/w of the compound of Formula (I)
or salt or solvate thereof;
b) 0-95% w/w of microcrystalline cellulose;
c) 0-95% w/w of lactose monohydrate;
d) 0.5-10% w/w of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS);
e) 0-10 5 w/w of sodium starch glycolate;
d) 0-5% w/w of hydroxypropylcellulose; and
e) 0.25-1.5 of magnesium stearate.