In vivo studies of crystalline forms of meloxicam

1. A crystalline form of meloxicam, which has improved bioavailability, an enhanced rate of dissolution and shorter time to C max in blood when compared to the bioavailability, rate of dissolution, and time to C max , of marketed pure meloxicam, selected from the group consisting of co-crystal meloxicam:fumaric acid, co-crystal meloxicam:succinic acid, co-crystal meloxicam:adipic acid; co-crystal meloxicam:benzoic acid, co-crystal meloxicam:DL-malic acid, co-crystal meloxicam:L-malic acid, co-crystal meloxicam:glutaric acid, co-crystal meloxicam:acetylsalicylic acid, co-crystal meloxicam:salicylic acid form I, co-crystal meloxicam:salicylic acid form II, co-crystal meloxicam:salicylic acid form III, co-crystal meloxicam:1-hydroxy-2-naphthoic acid, co-crystal meloxicam:maleic acid, co-crystal meloxicam:4-hydroxybenzoic acid, co-crystal meloxicam:malonic acid, co-crystal meloxicam:glycolic acid, co-crystal meloxicam:2,5-dihydroxybenzoic acid form I, co-crystal meloxicam:2,5-dihydroxybenzoic acid form II, co-crystal meloxicam:camphoric acid form I, co-crystal meloxicam:camphoric acid form II, co-crystal meloxicam:maltol, co-crystal meloxicam :ethyl maltol, and co-crystal meloxicam:hydrocinnamic acid.

2. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:fumaric acid which: a) has a PXRD diffraction pattern with peaks at about 12.13, 14.75, 16.52, 18.14, 22.21, 23.53 and 26.86+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 1 .

3. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:succinic acid which: a) has a PXRD diffraction pattern with peaks at about 13.22, 14.50, 16.41, 18.30, 23.68, 26.59 and 27.67+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 3 .

4. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:adipic acid which: a) has a PXRD diffraction pattern with peaks at about 8.56, 9.38, 12.67, 17.50, 24.13, 26.77, and 27.46 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 5 .

5. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:benzoic acid which: a) has a PXRD diffraction pattern with peaks at about 9.61, 14.06, 15.00, 16.01, 17.21, 18.20 and 26.47+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 7 .

6. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:DL-malic acid which: a) has a PXRD diffraction pattern with peaks at about 13.39, 14.87, 16.55, 18.39, 23.78, 26.80 and 27.91+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 9 .

7. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:L-malic acid which: a) has a PXRD diffraction pattern with peaks at about 13.14, 14.57, 16.25, 23.51, 24.66, 26.53 and 27.66+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 11 .

8. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:glutaric acid which: a) has a PXRD diffraction pattern with peaks at about 5.16, 13.85, 15.26, 16.13, 19.64, 26.17 and 27.58+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 13 .

9. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:acetylsalicylic acid which: a) has a PXRD diffraction pattern with peaks at about 9.57, 13.55, 14.18, 19.49, 22.51, 23.86 and 24.88 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 15 .

10. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:salicylic acid form I which: a) has a PXRD diffraction pattern with peaks at about 12.08, 13.85, 14.75, 16.10, 25.24, 25.87 and 27.00 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 17 .

11. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:salicylic acid form II which: a) has a PXRD diffraction pattern with peaks at about 6.27, 15.02, 15.47, 19.70, 25.66, 26.23 and 27.49 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 19 .

12. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:salicylic acid form III which: a) has a PXRD diffraction pattern with peaks at about 9.57, 13.55, 14.18, 19.49, 22.51, 23.86 and 24.88 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 41 .

13. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:1-hydroxy-2-naphthoic acid which: a) has a PXRD diffraction pattern with peaks at about 6.67, 12.35, 14.92, 16.25, 17.75, 25.93 and 26.88+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 21 .

14. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:maleic acid which: a) has a PXRD diffraction pattern with peaks at about 8.27, 15.50, 16.35, 18.59, 21.43, 22.58 and 25.69+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 23 .

15. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:4-hydroxybenzoic acid which: a) has a PXRD diffraction pattern with peaks at about 6.88, 7.92, 13.34, 17.87, 19.41, 25.36 and 26.86 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 25 .

16. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:malonic acid which: a) has a PXRD diffraction pattern with peaks at about 9.74, 11.88, 14.06, 15.02, 19.34, 22.27 and 26.83+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 27 .

17. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:glycolic acid which: a) has a PXRD diffraction pattern with peaks at about 10.91, 14.18, 14.87, 15.56, 19.28, 21.37 and 26.38+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 29 .

18. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:2,5-dihydroxybenzoic acid form I which: a) has a PXRD diffraction pattern with peaks at about 9.77, 14.96, 18.84, 22.85, 24.43, 25.12 and 29.02+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 31 .

19. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:2,5-dihydroxybenzoic acid form II which: a) has a PXRD diffraction pattern with peaks at about 9.86, 15.05, 19.07, 19.79, 22.99, 25.27 and 26.32+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 33 .

20. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:camphoric acid form I which: a) has a PXRD diffraction pattern with peaks at about 7.68, 11.35, 13.64, 15.47, 26.23 and 26.83+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 35 .

21. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:camphoric acid form II which: a) has a PXRD diffraction pattern with peaks at about 5.19, 9.95, 11.41, 13.50, 15.38, 16.70, 26.23 and 36.21+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 37 .

22. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:maltol which: a) has a PXRD diffraction pattern with peaks at about 9.41, 12.83, 14.87, 16.37, 23.39, 25.78 and 28.88+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 39 .

23. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:ethyl maltol which: a) has a PXRD diffraction pattern with peaks at about 6.67, 12.35, 14.92, 16.25, 17.75, 25.93 and 26.88+/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 43 .

24. The crystalline form of meloxicam of claim 1 , wherein said crystalline form is co-crystal meloxicam:hydrocinnamic acid which: a) has a PXRD diffraction pattern with peaks at about 8.27, 15.50, 16.35, 18.59, 21.43, 22.58 and 25.69 +/−0.2 degrees two-theta; and/or b) has a PXRD diffraction pattern as depicted in FIG. 45 .

25. A solid pharmaceutical composition comprising an effective amount of one or more of the crystalline forms of meloxicam of claim 1 and a pharmaceutically acceptable excipient.