Solid forms comprising 3-(4-amino-1-OXO-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and a coformer, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9808450-B2
Application number	US-201414780495-A
Country	US
Kind code	B2
Filing date	Mar 25, 2014
Priority date	Mar 26, 2013
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

Provided herein are solid forms comprising (a) 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (Lenalidomide) and (b) a coformer. Pharmaceutical compositions comprising the solid forms and methods for treating, preventing and managing various disorders are also disclosed.

First claim

What is claimed is:

1. A crystalline solid form comprising (a) 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, prodrug, or clathrate thereof; and (b) a coformer; wherein the coformer is benzoic acid, glycolic acid, hippuric acid, magnesium bromide, sodium lauryl sulfate, vanillic acid, or zinc chloride.

2. The solid form of claim 1 , wherein the coformer is benzoic acid.

3. The solid form of claim 1 , wherein the coformer is glycolic acid.

4. The solid form of claim 1 , wherein the coformer is hippuric acid.

5. The solid form of claim 1 , wherein the coformer is magnesium bromide.

6. The solid form of claim 1 , wherein the coformer is sodium lauryl sulfate.

7. The solid form of claim 1 , wherein the coformer is vanillic acid.

8. The solid form of claim 1 , wherein the coformer is zinc chloride.

9. The solid form of claim 1 , wherein the molar ratio of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione to the coformer is about 1:1.

10. The solid form of claim 1 , which is greater than 80% by weight, greater than 90% by weight, greater than 95% by weight, greater than 97% by weight, or greater than 99% by weight a cocrystal.

11. The solid form of claim 1 , which is substantially physically pure.

12. The solid form of claim 11 , which is substantially free of other solid forms of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione.

13. The solid form of claim 1 , which is substantially chemically pure.

14. The solid form of claim 1 , which is substantially free of solvent.

15. The solid form of claim 1 , which is substantially free of water.

16. The solid form of claim 1 , further comprising amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione.

17. The solid form of claim 1 , which is stable.

18. The solid form of claim 1 , which is thermally stable.

19. A pharmaceutical composition comprising the solid form of claim 1 .

20. The pharmaceutical composition of claim 19 , further comprising a pharmaceutically acceptable excipient or carrier.

21. The pharmaceutical composition of claim 19 , which is a single unit dosage form.

22. The pharmaceutical composition of claim 19 , which is a tablet.

23. The pharmaceutical composition of claim 19 , which is a capsule.

24. The pharmaceutical composition of claim 19 , wherein 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is in an amount of from about 0.1 to about 5 mg.

25. The solid form of claim 2 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and benzoic acid, and having an XRPD pattern comprising peaks at approximately 16.18 and 32.80 degrees 2θ.

26. The solid form of claim 25 , wherein the XRPD pattern further comprises peaks at approximately 15.07 and 24.42 degrees 2θ.

27. The solid form of claim 3 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and glycolic acid, and having an XRPD pattern comprising peaks at approximately 9.85, 22.89, and 25.39 degrees 2θ.

28. The solid form of claim 27 , wherein the XRPD pattern further comprises peaks at approximately 20.58, 24.13, and 29.48 degrees 2θ.

29. The solid form of claim 4 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and hippuric acid, and having an XRPD pattern comprising peaks at approximately 13.12, 21.42, and 28.89 degrees 2θ.

30. The solid form of claim 29 , wherein the XRPD pattern further comprises peaks at approximately 22.10, 27.56, and 35.27 degrees 2θ.

31. The solid form of claim 5 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and magnesium bromide, and having an XRPD pattern comprising peaks at approximately 15.75, 21.98, and 28.76 degrees 2θ.

32. The solid form of claim 31 , wherein the XRPD pattern further comprises peaks at approximately 18.63, 24.27, and 25.71 degrees 2θ.

33. The solid form of claim 6 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and sodium lauryl sulfate, and having an XRPD pattern comprising peaks at approximately 2.19, 2.69, and 5.34 degrees 2θ.

34. The solid form of claim 33 , wherein the XRPD pattern further comprises peaks at approximately 8.00, 17.66, and 20.62 degrees 2θ.

35. The solid form of claim 7 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and vanillic acid, and having an XRPD pattern comprising peaks at approximately 12.06, 15.77, and 20.70 degrees 2θ.

36. The solid form of claim 35 , wherein the XRPD pattern further comprises peaks at approximately 10.30 and 31.26 degrees 2θ.

37. The solid form of claim 8 , comprising 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione and zinc chloride, and having an XRPD pattern comprising peaks at approximately 17.27, 18.00, and 24.46 degrees 2θ.

38. The solid form of claim 37 , wherein the XRPD pattern further comprises peaks at approximately 15.80, 20.82, and 22.33 degrees 2θ.

Assignees

• Celgene Corp

Inventors

• Stahly G Patrick
• Jonaitis David
• Hui Ho-Wah
• Klopfer Kevin J

Classifications

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/454 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title