Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione

• US 8,431,598 B2
• Filed: 05/26/2011
• Issued: 04/30/2013
• Est. Priority Date: 09/04/2003
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Jaworsky, Markian S., Chen, Roger Shen-Chu, Muller, George W.
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US13/117,066
• Publication Number:
  US 20110288127A1
• Time in Patent Office: 705 Days
• Field of Search: 514/323, 546/201
• US Class Current: 514/323
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B65D 51/2864 the element being a plug or like element closing a passage between the auxiliary container and the main container
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond

Abstract

Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione are disclosed. Compositions comprising the polymorphic forms, methods of making the polymorphic forms and methods of their use are also disclosed.

Claims

1. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline Form A of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C., wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

2. The solid form of claim 1, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

3. The solid form of claim 1, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

4. The solid form of claim 1, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

14. A pharmaceutical composition comprising a therapeutically effective amount of the solid form of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, and 13, and a pharmaceutically acceptable excipient, diluent, or carrier.

15. The pharmaceutical composition of claim 14, which is a single unit dosage form.

16. The pharmaceutical composition of claim 15, wherein the therapeutically effective amount is about 5 mg, about 10 mg, about 25 mg, or about 50 mg.

5. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C. and an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, and 16 degrees 2θ and

a thermogravimetric analysis curve indicative of an unsolvated material, wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

6. The solid form of claim 5, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

7. The solid form of claim 5, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

8. The solid form of claim 5, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

9. The solid form of any one of claims 5, 6, 7, and 8, wherein the X-ray powder diffraction pattern further comprises peaks at approximately 17.5, 20.5, 24 and 26 degrees 2θ

.

10. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ

, wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

11. The solid form of claim 10, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

12. The solid fault of claim 10, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

13. The solid form of claim 10, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

17. A pharmaceutical composition comprising from about 5 mg to about 25 mg of a solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C., and a pharmaceutically acceptable excipient, diluent, or carrier;

wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

18. The pharmaceutical composition of claim 17, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

19. The pharmaceutical composition of claim 17, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

20. The pharmaceutical composition of claim 17, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

21. The pharmaceutical composition of any one of claims 17, 18, 19, and 20, comprising about 5 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

22. The pharmaceutical composition of any one of claims 17, 18, 19, and 20, comprising about 10 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

23. The pharmaceutical composition of any one of claims 17, 18, 19, and 20, comprising about 25 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.