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

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.

1 .- 28 . (canceled) 
     
     
         29 . A composition comprising amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl )-piperidine-2,6-dione and crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate. 
     
     
         30 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has an X-ray powder diffraction pattern comprising peaks at approximately 20, 24.5, and 29 degrees 2θ. 
     
     
         31 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has an X-ray powder diffraction pattern comprising peaks at approximately 20.0, 24.7, and 28.6 degrees 2θ. 
     
     
         32 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 23 . 
     
     
         33 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 35 . 
     
     
         34 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at about 269° C. 
     
     
         35 . The composition of  claim 34 , wherein the thermogram further comprises an endotherm at about 99° C. 
     
     
         36 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 24 . 
     
     
         37 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 45 . 
     
     
         38 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate that has a thermal gravimetric analysis curve comprising a weight loss of about 12% up to about 175° C. 
     
     
         39 . The composition of  claim 29 , wherein the composition comprises:
 a) less than 50% by weight of amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione; and   b) greater than 50% by weight of crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate.   
     
     
         40 . The composition of  claim 29 , wherein the composition comprises:
 a) less than 25% by weight of amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione; and   b) greater than 75% by weight of crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate.   
     
     
         41 . The composition of  claim 29 , wherein the composition comprises:
 a) less than 10% by weight of amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione; and   b) greater than 90% by weight of crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate.   
     
     
         42 . The composition of  claim 29 , wherein the composition comprises:
 a) less than 5% by weight of amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione; and   b) greater than 95% by weight of crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate.