Crystals and process of making 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid

• US 9,789,125 B2
• Filed: 06/02/2016
• Issued: 10/17/2017
• Est. Priority Date: 07/09/2007
• Status: Active Grant

• Current Assignee: Allergan Holdings Unlimited Company (Abbvie Incorporated)
• Original Assignee: Allergan Holdings Unlimited Company (Abbvie Incorporated)
• Inventors: Anzalone, Luigi, Villani, Frank J., Teleha, Christopher A., Feibush, Penina, Fegely, Barry
• Primary Examiner(s): VAJDA, KRISTIN ANN
• Application Number:
  US15/171,967
• Publication Number:
  US 20160354389A1
• Time in Patent Office: 502 Days
• Field of Search: 514400, 548400, 5483381
• CPC Class Codes: A61K 31/625 having heterocyclic substituents, e.g. 4-salicycloylmorpholine, sulfasalazine A61K31/635
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Abstract

The present invention relates to a novel crystals of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1h-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid and methods of making the zwitterion of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1h-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.

Claims

1. A pharmaceutical composition comprising a Form α

crystal of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 10.2±

0.3, 11.3±

0.3, 11.8±

0.3, 14.0±

0.3, 14.3±

0.3, 14.7±

0.3, 16.1±

0.3, and 18.3±

0.3 degrees 2-theta.

2. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 10.2±

0.25, 11.3±

0.25, 11.8±

0.25, 14.0±

0.25, 14.3±

0.25, 14.7±

0.25, 16.1±

0.25, and 18.3±

0.25 degrees 2-theta.

3. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 10.2±

0.2, 11.3±

0.2, 11.8±

0.2, 14.0±

0.2, 14.3±

0.2, 14.7±

0.2, 16.1±

0.2, and 18.3±

0.2 degrees 2-theta.

4. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 14.0±

0.2, 14.3±

0.2, 14.7±

0.2 degrees 2-theta.

5. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 10.2±

0.2, 11.3±

0.2, 14.0±

0.2, 14.3±

0.2, and 14.7±

0.2 degrees 2-theta.

6. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 10.2±

0.2, 11.3±

0.2, 11.8±

0.2, 14.0±

0.2, 14.3±

0.2, 14.7±

0.2, 16.1±

0.2, and 18.3±

0.2 degrees 2-theta.

7. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks substantially as shown in Table 1.

8. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks substantially similar to the powder X ray diffraction peaks of FIG. 1.

9. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a thermal gravimetric analysis (TGA) substantially similar to the TGA in FIG. 2.

10. The pharmaceutical composition of claim 1, wherein the Form α

crystal is characterized by a differential scanning calorimetry (DSC) measurement substantially similar to the DSC in FIG. 3.

11. The pharmaceutical composition of claim 1, in a dosage form suitable for oral administration.

12. The pharmaceutical composition of claim 11, wherein the dosage form is a solid.

13. The pharmaceutical composition of claim 11, wherein the dosage form is selected from the group consisting of a tablet, a caplet, a hard gelatin capsule, a starch capsule, a hydroxypropyl methylcellulose (HPMC) capsule, and a soft elastic gelatin capsule.

14. The pharmaceutical composition of claim 11, wherein the dosage form as administered is a liquid.

15. The pharmaceutical composition of claim 11, wherein the dosage form as administered is selected from the group consisting of a suspension, a solution, a syrup, and an emulsion.

16. The pharmaceutical composition of claim 11, wherein the dosage form is a tablet.

17. A method of treating an opioid receptor disorder in a mammal comprising administering to the mammal an effective amount of the pharmaceutical composition of claim 1.

18. The method of claim 17, wherein the opioid receptor disorder is selected from the group consisting of irritable bowel syndrome, pain and a combination of both.

19. The method of claim 17, wherein the opioid receptor disorder is irritable bowel syndrome.

20. The method of claim 17, wherein the opioid receptor disorder is pain.

21. A pharmaceutical composition comprising a Form β

crystal of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 11.0±

0.3, 12.4±

0.3, 14.9±

0.3, 15.2±

0.3, 22.1±

0.3, 25.6±

0.3, 27.4±

0.3, and 30.4±

0.3 degrees 2-theta.

22. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 11.0±

0.25, 12.4±

0.25, 14.9±

0.25, 15.2±

0.25, 22.1±

0.25, 25.6±

0.25, 27.4±

0.25, and 30.4±

0.25 degrees 2-theta.

23. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having any three or more powder X-ray diffraction peaks selected from the group consisting of powder X-ray diffraction peaks at about 11.0±

0.2, 12.4±

0.2, 14.9±

0.2, 15.2±

0.2, 22.1±

0.2, 25.6±

0.2, 27.4±

0.2, and 30.4±

0.2 degrees 2-theta.

24. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 11.0±

0.2, 12.4±

0.2, and 15.2±

0.2 degrees 2-theta.

25. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 11.0±

0.2, 12.4±

0.2, 14.9±

0.2, 15.2±

0.2, and 22.1±

0.2, degrees 2-theta.

26. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks at about 11.0±

0.2, 12.4±

0.2, 14.9±

0.2, 15.2±

0.2, 22.1±

0.2, 25.6±

0.2, 27.4±

0.2, and 30.4±

0.2 degrees 2-theta.

27. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks substantially as shown in Table 2.

28. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a powder X-ray diffraction pattern having powder X-ray diffraction peaks substantially similar to the powder X ray diffraction peaks of FIG. 1.

29. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a thermal gravimetric analysis (TGA) substantially similar to the TGA in FIG. 4.

30. The pharmaceutical composition of claim 21, wherein the Form β

crystal is characterized by a differential scanning calorimetry (DSC) measurement substantially similar to the DSC in FIG. 5.

31. The pharmaceutical composition of claim 21, in a dosage form suitable for oral administration.

32. The pharmaceutical composition of claim 31, wherein the dosage form is a solid.

33. The pharmaceutical composition of claim 31, wherein the dosage form is selected from the group consisting of a tablet, a caplet, a hard gelatin capsule, a starch capsule, a hydroxypropyl methylcellulose (HPMC) capsule, and a soft elastic gelatin capsule.

34. The pharmaceutical composition of claim 31, wherein the dosage form as administered is a liquid.

35. The pharmaceutical composition of claim 31, wherein the dosage form as administered is selected from the group consisting of a suspension, a solution, a syrup, and an emulsion.

36. The pharmaceutical composition of claim 31, wherein the dosage form is a tablet.

37. A method of treating an opioid receptor disorder in a mammal comprising administering to the mammal an effective amount of the pharmaceutical composition of claim 21.

38. The method of claim 37, wherein the opioid receptor disorder is selected from the group consisting of irritable bowel syndrome, pain and a combination of both.

39. The method of claim 37, wherein the opioid receptor disorder is irritable bowel syndrome.

40. The method of claim 37, wherein the opioid receptor disorder is pain.