SALT OF 4-[[4-[[4-(2-CYANOETHENYL)-2,6-DIMETHYLPHENYL]AMINO]-2-PYRIMIDINYL]AMINO]BENZONITRILE

• US 20110008434A1
• Filed: 07/28/2010
• Published: 01/13/2011
• Est. Priority Date: 08/13/2001
• Status: Active Grant

• Current Assignee: Alex Herman Copmans, Alfred Elisabeth Stappers, Jérôme Emile Georges Guillemont, Jozef Peeters, Paul Stoffels, Paul Theodoor Agnes Stevens, Roger Petrus Gerebern Vandecruys
• Original Assignee: Alex Herman Copmans, Alfred Elisabeth Stappers, Jérôme Emile Georges Guillemont, Jozef Peeters, Paul Stoffels, Paul Theodoor Agnes Stevens, Roger Petrus Gerebern Vandecruys
• Inventors: Stappers, Alfred Elisabeth, Stoffels, Paul, Peeters, Jozef, Vandecruys, Roger Petrus Gerebern, Stevens, Paul Theodoor Agnes, Copmans, Alex Herman, GUILLEMONT, Jérôme Emile Georges
• Granted Patent: US 8,101,629 B2
• Time in Patent Office: Days
• US Class Current: 424/474
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07D 239/48 Two nitrogen atoms

Abstract

The present invention relates to a pharmaceutical composition comprising as active ingredient the hydrochloric acid salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethyl-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile and to processes for their preparation.

Claims

1-14. -14. (canceled)

15. A tablet comprising 25 mg base equivalent of a compound of formula (I-a)

16. A tablet according to claim 15 wherein the compound of formula (I-a) is polymorphic Form A characterized by X-ray powder diffraction peaks at two-theta positions 9.7°

±

0.2°

, 13.5°

±

0.2° and

15.0°

±

0.2°

.

17. A tablet according to claim 16 wherein the polymorphic Form A is further characterized by X-ray powder diffraction peaks at two-theta positions 9.1°

±

0.2°

, 11.0°

±

0.2°

, 14.6°

±

0.2°

, 22.0°

±

0.2°

, 25.0°

±

0.2°

, 25.3°

±

0.2° and

26.7°

±

0.2°

.

18. A tablet according to claim 16 wherein the polymorphic Form A is characterized by an FTIR spectrum with absorption bands at about 2217, 1652, 1497, 1435, 1338, 1199 and 550 cm⁻

1.

19. A tablet according to claim 18 wherein polymorphic Form A is further characterized by an FTIR spectrum with absorption bands at 1631, 1596, 1537, 1504, 1249, 1214, 1179 , 1152 and 1070 cm⁻

1.

20. A tablet according to claim 15 wherein the wetting agent is polysorbate 20.

21. A tablet according to claim 15 which is film-coated.

22. A tablet according to claim 15 wherein the tablet comprises a tablet core having the following composition:

23. A tablet according to claim 15 wherein the tablet comprises a tablet core having the following composition:

32. A tablet according to claim 15 wherein the compound of formula (I-a) has a particle size of less than 50 μ

m.

33. A tablet according to claim 15 wherein the compound of formula (I-a) has a particle size of less than 25 μ

m.

34. A particle of compound of formula (I-a) as defined in claim 15, said particle having a particle size of less than 50 μ

m.

35. A particle according to claim 34 wherein the particle has a particle size of less than 25 μ

m.

24. A tablet comprising 50 mg base equivalent of a compound of formula (I-a)

25. A tablet according to claim 24 wherein the tablet comprises a tablet core having the following composition:

Compound of formula (I-a) 55 mg

Lactose monohydrate 214.5 mg

Hypromellose 2910 15mPa·

s 5.6 mg

Polysorbate 20 1.4 mg

Microcrystalline cellulose 52.5 mg

Croscarmellose sodium 17.5 mg

Colloidal silicon dioxide 1.05 mg

Magnesium stearate 2.45 mg

26. A tablet comprising 75 ma base equivalent of a compound of formula (I-a)

27. A tablet according to claim 26 wherein the tablet comprises a tablet core having the following composition:

28. A tablet comprising 100 mg base equivalent of a compound of formula (I-a)

29. A tablet according to claim 28 wherein the tablet comprises a tablet core having the following composition:

30. A tablet comprising 150 mg base equivalent of a compound of formula (I-a)

31. A tablet according to claim 30 wherein the tablet comprises a tablet core having the following composition: