THERAPEUTIC FORMULATIONS AND USES THEREOF
Provided herein are pharmaceutically acceptable compositions containing a selective cyclooxygenase-2 (COX-2) inhibitor (coxib) and optionally buprenorphine. In particular, compositions containing a coxib formulated for oral, topical or subcutaneous administration to treat pain or inflammation are described.
1 . A pharmaceutical composition for oral administration, comprising:
a) a cyclooxygenase-2 (COX-2) inhibitor of Formula (II):
or an isomer or pharmaceutically acceptable salt thereof; and
b) a pharmaceutically acceptable carrier, wherein the composition is formulated as a liquid suspension, a solid or semi-solid oral dosage form.
2 . The composition of claim 1 , wherein the pharmaceutically acceptable salt of the COX-2 inhibitor is Tris(hydroxymethyl)aminomethane (±)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate.
3 . The composition of claim 2 , wherein the pharmaceutically acceptable salt of the COX-2 inhibitor is micronized.
4 . The composition of claim 1 , wherein at least about 5,000, 10,000, 15,000 or 20,000 ng/ml of the COX-2 inhibitor is present in the blood stream of a subject after administration.
5 . The composition of claim 1 , wherein the COX-2 inhibitor is present in the blood stream for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater after administration to a subject.
6 . The composition of claim 1 , further comprising a glidant.
7 . The composition of claim 6 , wherein the glidant is colloidal silicon dioxide.
8 . The composition of claim 7 , wherein the colloidal silicon dioxide is present from about 0 to 10% w/w of the composition.
9 . The composition of claim 1 , further comprising a disintegrant.
10 . The composition of claim 9 , wherein the disintegrant is sodium starch glycolate.
11 . The composition of claim 10 , wherein the disintegrant is present from about 0 to 20% w/w of the composition.
12 . The composition of claim 11 , wherein the disintegrant is present from about 2.5% w/w of the composition.
13 . The composition of claim 1 , further comprising a lubricant.
14 . The composition of claim 13 , wherein the lubricant is a stearic acid lubricant.
15 . The composition of claim 14 , wherein the stearic acid lubricant is present at 0 to 50% w/w.
16 . The composition of claim 15 , wherein the stearic acid lubricant is present at about 0.5% w/w.
17 . A pharmaceutical composition for oral administration, comprising:
a) a cyclooxygenase-2 (COX-2) inhibitor of Formula (II):
or an isomer or pharmaceutically acceptable salt thereof;
b) a pharmaceutically acceptable carrier, wherein the composition is formulated as a liquid suspension, a solid or semi-solid oral dosage form;
c) colloidal silicone dioxide;
d) sodium starch glycolate; and
e) a stearic acid lubricant.
18 . The composition of claim 17 , wherein the COX-2 inhibitor is present at about 50% w/w.
19 . The composition of claim 17 , wherein the composition comprises a weight of about 250, 375, 1000 and 1500 mg.
20 . The composition of claim 17 , wherein the silicon dioxide is present from 0 to 10% w/w.
21 . The composition of claim 20 , wherein the silicon dioxide is present at 0.5% w/w.
22 . The composition of claim 17 , wherein the sodium starch glycolate is present from 0 to 20% w/w.
23 . The composition of claim 22 , wherein the sodium starch glycolate is present at about 2.5% w/w.
24 . The composition of claim 22 , wherein the stearic acid lubricant is present at about 0.5% w/w.
25 . A method of treating a disease or disorder in a subject, comprising administering to the subject a therapeutically effective amount of a composition of claim 1 .
26 . The method of claim 25 , wherein the therapeutically effective amount of the composition is administered in a single dose.
27 . The method of claim 26 , wherein the single dose is from about 0.1 to 20.0 mg/kg, about 0.2 to 15 mg/kg, about 1 to 15 mg/kg, about 3 to 10 mg/kg, about 1 to 5 mg/kg, or about 3 to 5 mg/kg.
28 . The method of claim 25 , wherein the disease or disorder is pain or inflammation.
29 . The composition of claim 1 , wherein the composition is a single dose.
30 . The composition of claim 29 , wherein the single dose comprises the COX-2 inhibitor from about 0.1 to 20.0 mg/kg, about 0.2 to 15 mg/kg, about 1 to 15 mg/kg, about 3 to 10 mg/kg, about 1 to 5 mg/kg, or about 3 to 5 mg/kg.