Topical compositions containing rofecoxib and methods of making and using the same

1. A topical composition comprising a therapeutically effective amount of from 0.1% w/w to 2.5% w/w rofecoxib dissolved in between about 0.1% w/w and about 15% w/w isosorbide dimethyl ether (DI) and between about 0.1% w/w and about 5% w/w propylene carbonate (PC), and wherein the composition comprises a moisturizing agent selected from the group consisting of oleic acid, beeswax, polysorbate 20 and mineral oil.

2. The topical composition of claim 1 , comprising one or more additional pharmaceutically acceptable solvents selected from the group consisting of acetone (AC), 2-methylpentane-2,4-diol (M24D), alpha-terpineol (AT), benzyl alcohol (BA), diethyl sebacate (DS), diethylene glycol monoethyl ether (DGME), diisopropyl adipate (DIA), dimethyl sulfoxide (DMSO), ethyl acetate (EA), isopropyl tetradecanoate (IPTD), N-methyl-2-pyrrolidone (MP), polyethylene glycol 400 (PEG), polysorbate 20 (PS20), polysorbate 80 (PS80), propylene glycol diacetate (PGD), and propylene glycol (PPG).

3. The topical composition of claim 1 , wherein the composition comprises about 15% w/w DI.

4. The topical composition of claim 1 , wherein the composition comprises about 5% w/w PC.

5. The topical composition of claim 1 , wherein the composition comprises about w/w DI and about 5 w/w PC.

6. The topical composition of claim 1 , wherein the therapeutically effective amount of rofecoxib is about 2% w/w.

7. The topical composition of claim 1 , wherein the therapeutically effective amount of rofecoxib is about 1% w/w.

8. The topical composition of claim 1 , wherein the therapeutically effective amount of rofecoxib is about 0.5% w/w.

9. The topical composition of claim 1 , comprising from about 0.1% benzyl alcohol (BA) to about 2% w/w BA.

10. The topical composition of claim 9 , comprising about 2% w/w BA.

11. The topical composition of claim 1 , further comprising dimethyl sulfoxide (DMSO).

12. The topical composition of claim 1 , further comprising diisopropyl adipate (DIA).

13. The topical composition of claim 1 , further comprising diethylene glycol monoethyl ether (DGME).

14. The topical composition of claim 1 , further comprising polysorbate 20 (PS20).

15. The topical composition of claim 1 , further comprising oleic acid (OA).

16. The topical composition of claim 1 , comprising about 2 w/w benzyl alcohol (BA), about 10% w/w dimethyl sulfoxide (DMSO), and about 10% w/w diisopropyl adipate (DIA).

17. The topical composition of claim 16 , further comprising about 15% w/w polysorbate 20 (PS20).

18. The topical composition of claim 16 , further comprising about 7.5% w/w oleic acid (OA).

19. The topical composition of claim 16 , further comprising from about 0.1% w/w to about 40% w/w diethylene glycol monoethyl ether (DGME).

20. The topical composition of claim 1 , further comprising one or more additional ingredients selected from the group consisting of a humectant, a chelating agent, a UV absorption agent, a moisturizing agent, an excipient, a preservative, a thickening agent, a silicone containing compound, an essential oil, a structuring agent, a vitamin, a pharmaceutical ingredient, and an antioxidant.

21. The topical composition of claim 1 , wherein the topical composition is selected from the group consisting of: Formulations 30, 36, 41, 50, 53, 57-59, and 85, wherein:

Formulation 30 comprises DI (14.8% w/w), PC (4.9% w/w), BA (2.6% w/w), oleic acid (OA) (4.9% w/w), DMSO (8.9% w/w), beeswax (3.4% w/w), lanolin (9.9% w/w), mineral oil (48.1% w/w), and rofecoxib (1.9% w/w);

Formulation 36 comprises DI (15% w/w), PC (5% w/w), DMSO (9.1% w/w), BA (2.6% w/w), OA (5% w/w), Lanolin (10% w/w), Mineral Oil (47.8% w/w), beeswax (3.5% w/w), and rofecoxib (2% w/w);

Formulation 41 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w), DMSO (10% w/w), OA (5% w/w), PEG-400 (61% w/w), and rofecoxib (2% w/w);

Formulation 50 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w), DMSO (10% w/w), OA (5% w/w), polyethylene glycol 400 (PEG-400) (40% w/w), ethyl acetate (EA) (21% w/w), and rofecoxib (2% w/w);

Formulation 53 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w) DMSO (10% w/w), OA (5% w/w), PEG-400 (49% w/w), DIA (12% w/w), and rofecoxib (2% w/w),

Formulation 57 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w), DMSO (10% w/w), OA (5% w/w), DIA (10% w/w), PEG-400 (52% w/w), and rofecoxib (1% w/w);

Formulation 58 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w), DMSO (10% w/w), OA (5% w/w), DIA (10% w/w), PEG-400 (51% w/w), and rofecoxib (2% w/w);

Formulation 59 comprises DI (15% w/w), PC (5% w/w), BA (2% w/w), DMSO (15% w/w), OA (5% w/w), DIA (10% w/w), PEG-400 (47% w/w), and rofecoxib (1% w/w), and

Formulation 85 comprises DI (15% A w/w); PC (5% w/w); BA (2.5% w/w): DMSO (20% w/w); DIA (12% w/w); DGME (18.5% w/w); PS20 (15% w/w); OA (5% w/w); Hydroxypropyl cellulose 100,000 (4% w/w); rofecoxib 2% (2% w/w); eucalyptus oil (0.33% w/w); and spearmint oil (0.67% w/w).

22. The topical composition of claim 1 , wherein the topical composition is Formulation 85, wherein Formulation 85 comprises DI (15% w/w); PC (5% w/w); benzyl alcohol (BA) (2.5% w/w): dimethyl sulfoxide (DMSO) (20% w/w): diisopropyl adipate (DIA) (12% w/w); diethylene glycol monoethyl ether (DGME) (18.5% w/w); polysorbate 20 (PS20) (15% w/w); oleic acid (OA) (5% w/w); hydroxypropyl cellulose 100,000 (4% w/w); rofecoxib 2% (2% w/w): eucalyptus oil (0.33% w/w); and spearmint oil (0.67% w/w).

23. The topical composition of claim 1 , further comprising hydroxypropylcellulose (HPC).

24. The topical composition of claim 1 , further comprising eucalyptus oil.

25. The topical composition of claim 1 , further comprising spearmint oil.

26. A method of reducing inflammation, comprising topically applying the topical composition of claim 1 to the skin at the site of inflammation.

27. A method of treating arthritis in a joint, comprising topically applying the topical composition of claim 1 to the skin at the arthritic joint.

28. The topical composition of claim 1 , wherein the moisturizing agent is oleic acid.