Formulations
There is provided an alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide and formulations thereof. This salt finds particular utility in the treatment or prevention of a disorder or condition ameliorated by the activation of AMPK.
1. A pharmaceutical formulation, comprising:
particles comprising an alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide; and
at least one pharmaceutically acceptable excipient,
wherein the pharmaceutical formulation is coated with an enteric coating.
2. The pharmaceutical formulation of claim 1 , wherein the alkali metal salt is a sodium salt.
3. The pharmaceutical formulation of claim 1 , wherein the alkali metal salt is a potassium salt.
4. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation is a tablet.
5. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation is a capsule.
6. A pharmaceutical formulation, comprising:
(i) particles comprising an alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide, wherein the particles have a particle size distribution defined by a D90 of less than 10 μm; and
(ii) at least one pharmaceutically acceptable excipient.
7. The pharmaceutical formulation of claim 6 , further comprising an enteric coating.
8. The pharmaceutical formulation of claim 6 , wherein the alkali metal salt is a sodium salt.
9. The pharmaceutical formulation of claim 6 , wherein the alkali metal salt is a potassium salt.
10. The pharmaceutical formulation of claim 6 , wherein the pharmaceutical formulation is a tablet.
11. The pharmaceutical formulation of claim 6 , wherein the pharmaceutical formulation is a capsule.
12. A process for preparing a pharmaceutical formulation of claim 6 , the process comprising:
(i) milling the alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide—to obtain a particle size distribution defined by a D90 of less than 10 μm; and
(ii) combining the milled alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide with at least one pharmaceutically acceptable excipient to produce the pharmaceutical formulation.
13. The process according to claim 12 , wherein the process comprises dry milling.
14. The process according to claim 13 , wherein the dry milling involves jet milling.
15. An alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide wherein the cation:anion ratio is 1:1.
16. The alkali metal salt of claim 15 , wherein said salt is a salt of formula II,
or a tautomer thereof, wherein X represents an alkali metal.
17. The alkali metal salt of claim 15 , wherein the alkali metal is sodium.
18. The alkali metal salt of claim 15 , wherein the alkali metal is potassium.
19. A composition, comprising:
particles comprising an alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl) methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide, wherein the particles have a particle size distribution defined by a D90 of less than 10 μm.
20. The composition of claim 19 , wherein the alkali metal salt is a sodium salt.
21. The composition of claim 19 , wherein the alkali metal salt is a potassium salt.
22. The composition of claim 19 , wherein the particles are milled particles.
23. The composition of claim 22 , wherein the alkali metal salt is a sodium salt.
24. The composition of claim 22 , wherein the alkali metal salt is a potassium salt.
25. The composition of claim 19 , wherein the particles have one or more of the following:
a D50 of less than 6 μm; and
a D10 of less than 2 μm.
26. The composition of claim 25 , wherein the alkali metal salt is a sodium salt.
27. The composition of claim 19 , wherein the particles have one or more of the following:
a D50 of less than 5 μm; and
a D10 of less than 1.5 μm.
28. The composition of claim 27 , wherein the alkali metal salt is a sodium salt.
29. The pharmaceutical formulation of claim 10 , wherein the alkali metal salt is a sodium salt.
30. The process of claim 12 , wherein the alkali metal salt is a sodium salt.
31. The process of claim 12 , wherein the alkali metal salt is a potassium salt.
32. The process of claim 12 , wherein the pharmaceutical formulation is a tablet.
33. The process of claim 32 , wherein the alkali metal salt is a sodium salt.