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 method of reducing or preventing pain in a subject comprising: administering to the subject a single oral dose of a composition comprising:
a cyclooxygenase-2 (COX-2) inhibitor of Formula (II):
or an isomer or pharmaceutically acceptable salt thereof, prior to or immediately following an operative procedure, wherein the composition is formulated as a liquid suspension, a solid or semi-solid oral dosage form; and wherein the single oral dose is clinically effective to resolve pain for a duration of at least about 48 hours upon the single dose administration.
2 . The method 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 method of claim 2 , wherein the pharmaceutically acceptable salt of the COX-2 inhibitor is micronized.
4 . The method 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 method 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 method of claim 1 , wherein the composition further comprises a glidant.
7 . The method of claim 6 , wherein the glidant is colloidal silicon dioxide.
8 . The method of claim 7 , wherein the colloidal silicon dioxide is present from about 0 to 10% w/w of the composition.
9 . The method of claim 1 , wherein the composition further comprises a disintegrant.
10 . The method of claim 9 , wherein the disintegrant is sodium starch glycolate.
11 . The method of claim 10 , wherein the disintegrant is present from about 0 to 20% w/w of the composition.
12 . The method of claim 11 , wherein the disintegrant is present from about 2.5% w/w of the composition.
13 . The method of claim 1 , wherein the composition further comprises a lubricant.
14 . The method of claim 13 , wherein the lubricant is a stearic acid lubricant.
15 . The method of claim 14 , wherein the stearic acid lubricant is present at 0 to 50% w/w.
16 . The method of claim 15 , wherein the stearic acid lubricant is present at about 0.5% w/w.
17 . The method of claim 1 , wherein the composition comprises a weight of about 250, 375, 1000 or 1500 mg.
18 . The method of claim 1 , 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.
19 . The method of claim 1 , wherein the composition is in tablet or capsule form.
20 . The method of claim 1 , wherein the COX-2 inhibitor comprises about 10, 15, 40 or 60 mg in the composition.
21 . The method of claim 20 , wherein the COX-2 inhibitor comprises about 60 mg in the composition.
22 . The method of claim 1 , wherein the composition comprises:
a) a pharmaceutically acceptable carrier, wherein the composition is formulated as a liquid suspension, a solid or semi-solid oral dosage form;
b) colloidal silicon dioxide;
c) sodium starch glycolate; and
d) a stearic acid lubricant.
23 . The method of claim 22 , wherein the COX-2 inhibitor is present at about 50% w/w.
24 . The method of claim 22 , 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.
25 . The method of claim 22 , wherein the composition is in tablet or capsule form.
26 . The method of claim 22 , wherein the COX-2 inhibitor comprises about 10, 15, 40 or 60 mg in the composition.
27 . The method of claim 26 , wherein the COX-2 inhibitor comprises about 60 mg in the composition.