Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile

• US 8,101,629 B2
• Filed: 07/28/2010
• Issued: 01/24/2012
• Est. Priority Date: 08/13/2001
• Status: Expired due to Term

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Guillemont, Jérôme Emile Georges, Stevens, Paul Theodoor Agnes, Copmans, Alex Herman, Peeters, Jozef, Stappers, Alfred Elisabeth, Vandecruys, Roger Petrus Gerebern, Stoffels, Paul
• Primary Examiner(s): Balasubramanian, Venkataraman
• Application Number:
  US12/845,463
• Publication Number:
  US 20110008434A1
• Time in Patent Office: 545 Days
• Field of Search: 514/275, 544/323
• US Class Current: 514/275
• 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. A tablet comprising 25 mg base equivalent of a compound of formula (I-a)

2. A tablet according to claim 1 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°

.

3. A tablet according to claim 2 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°

.

4. A tablet according to claim 2 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.

5. A tablet according to claim 4 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.

6. A tablet according to claim 1 wherein the wetting agent is polysorbate 20.

7. A tablet according to claim 1 which is film-coated.

8. A tablet according to claim 1 wherein the tablet comprises a tablet core having the following composition:

9. A tablet according to claim 1 wherein the tablet comprises a tablet core having the following composition:

18. A tablet according to claim 1 wherein the compound of formula (I-a) has a particle size of less than 50 μ

m.

19. A tablet according to claim 1 wherein the compound of formula (I-a) has a particle size of less than 25 μ

m.

20. A particle of compound of formula (I-a) as defined in claim 1, said particle having a particle size of less than 50 μ

m.

21. A particle according to claim 20 wherein the particle has a particle size of less than 25 μ

m.

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

11. A tablet according to claim 10 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.

12. A tablet comprising 75 mg base equivalent of a compound of formula (I-a)

13. A tablet according to claim 12 wherein the tablet comprises a tablet core having the following composition:

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

15. A tablet according to claim 14 wherein the tablet comprises a tablet core having the following composition:

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

17. A tablet according to claim 16 wherein the tablet comprises a tablet core having the following composition: