Pharmaceutical co-crystal compositions
View Patent ↗A pharmaceutical composition comprising a co-crystal of an API and a co-crystal former; wherein the API has at least one functional group selected from ether, thioether, alcohol, thiol, aldehyde, ketone, thioketone, nitrate ester, phosphate ester, thiophosphate ester, ester, thioester, sulfate ester, carboxylic acid, phosphonic acid, phosphinic acid, sulfonic acid, amide, primary amine, secondary amine, ammonia, tertiary amine, sp2 amine, thiocyanate, cyanamide, oxime, nitrile diazo, organohalide, nitro, s-heterocyclic ring, thiophene, n-heterocyclic ring, pyrrole, o-heterocyclic ring, furan, epoxide, peroxide, hydroxamic acid, imidazole, pyridine and the co-crystal former has at least one functional group selected from amine, amide, pyridine, imidazole, indole, pyrrolidine, carbonyl, carboxyl, hydroxyl, phenol, sulfone, sulfonyl, mercapto and methyl thio, such that the API and co-crystal former are capable of co-crystallizing from a solution phase under crystallization conditions.
1. A co-crystal comprising an API and a co-crystal former selected from:
(a) carbamazepine and saccharin;
(b) carbamazepine and nicotinamide;
(c) carbamazepine and trimesic acid;
(d) celecoxib and nicotinamide;
(e) celecoxib and 18-crown-6;
(f) 5-fluorouracil and urea;
(g) acetaminophen and 4,4′-bipyridine;
(h) phenytoin and pyridone;
(i) aspirin and 4,4′-bipyridine;
(j) ibuprofen and 4,4′-bipyridine;
(k) flurbiprofen and 4,4′-bipyridine;
(l) flurbiprofen and trans-1,2-bis(4-pyridyl) ethylene;
(m) carbamazepine and p-phthalaldehyde;
(n) carbamazepine and 2,6-pyridinecarboxylic acid;
(o) carbamazepine and 5-nitroisoplithalic acid;
(p) carbamazepine and 1,3,5,7-adamantane tetracarboxylic acid; or
(q) carbamazepine and benzoquinone, wherein the API and co-crystal former are hydrogen bonded to each other.
2. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and saccharin.
3. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and nicotinamide.
4. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and trimesic acid.
5. The co-crystal according to claim 1 , wherein said co-crystal comprises celecoxib and nicotinamide.
6. The co-crystal according to claim 1 , wherein said co-crystal comprises celecoxib and 18-crown-6.
7. The co-crystal according to claim 1 , wherein said co-crystal comprises 5-fluorouracil and urea.
8. The co-crystal according to claim 1 , wherein said co-crystal comprises acetaminophen and 4,4′-bipyridine.
9. The co-crystal according to claim 1 , wherein said co-crystal comprises phenytoin and pyridine.
10. The co-crystal according to claim 1 , wherein said co-crystal comprises aspirin and 4,4′-bipyridine.
11. The co-crystal according to claim 1 , wherein said co-crystal comprises ibuprofen and 4,4′-bipyridine.
12. The co-crystal according to claim 1 , wherein said co-crystal comprises flurbiprofen and 4,4′-bipyridine.
13. The co-crystal according to claim 1 , wherein said co-crystal comprises flurbiprofen and trans-1,2-bis(4-pyridyl)ethylene.
14. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and p-phthalaldehyde.
15. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and 2,6-pyridinecarboxylic acid.
16. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and 5-nitroisophthalic acid.
17. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and 1,3,5,7-adamantane tetracarboxylic acid.
18. The co-crystal according to claim 1 , wherein said co-crystal comprises carbamazepine and benzoquinone.
19. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient, or carrier and a co-crystal comprising an API and a co-crystal former selected from:
(a) carbamazepine and saccharin;
(b) carbamazepine and nicotinamide;
(c) carbamazepine and trimesic acid;
(d) celecoxib and nicotinamide;
(e) celecoxib and 18-crown-6;
(f) 5-fluorouracil and urea;
(g) acetaminophen and 4,4′-bipyridine;
(h) phenytoin and pyridone;
(i) aspirin and 4,4′-bipyridine;
(j) ibuprofen and 4,4′-bipyridine;
(k) flurbiprofen and 4,4′-bipyridine;
(l) flurbiprofen and trans-1,2-bis(4-pyridyl)ethylene;
(m) carbamazepine and p-phthalaldehyde;
(n) carbamazepine and 2,6-pyridinecarboxylic acid;
(o) carbamazepine and 5-nitroisophthalic acid;
(p) carbamazepine and 1,3,5,7-adamantane tetracarboxylic acid; or
(q) carbamazepine and benzoquinone, wherein the API and co-crystal former hydrogen bonded to each other.
20. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and saccharin.
21. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and nicotinamide.
22. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and trimesic acid.
23. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises celecoxib and nicotinamide.
24. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises celecoxib and 18-crown-6.
25. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises 5-fluorouracil and urea.
26. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises acetaminophen and 4,4′-bipyridine.
27. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises phenytoin and pyridine.
28. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises aspirin and 4,4′-bipyridine.
29. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises ibuprofen and 4,4′-bipyridine.
30. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises flurbiprofen and 4,4′-bipyridine.
31. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises flurbiprofen and trans-1,2-bis(4-pyridyl)ethylene.
32. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and p-phthalaldehyde.
33. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and 2,6-pyridinecarboxylic acid.
34. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and 5-nitroisophthalic acid.
35. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and 1,3,5,7-adamantane tetracarboxylic acid.
36. The pharmaceutical composition according to claim 19 , wherein said co-crystal comprises carbamazepine and benzoquinone.