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 hemihydrate. 
     
     
         30 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has an X-ray powder diffraction pattern comprising peaks at approximately 16, 22, and 27 degrees 2θ. 
     
     
         31 . The composition of  claim 30 , wherein the crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate has an X-ray powder diffraction pattern further comprising a peak at approximately 18 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 hemihydrate that has an X-ray powder diffraction pattern comprising peaks at approximately 15.8, 22.2, and 26.7 degrees 2θ. 
     
     
         33 . The composition of  claim 32 , wherein the crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate has an X-ray powder diffraction pattern further comprising a peak at approximately 18.2 degrees 2θ. 
     
     
         34 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 6 . 
     
     
         35 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 32 . 
     
     
         36 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 33 . 
     
     
         37 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 34 . 
     
     
         38 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at about 268° C. 
     
     
         39 . The composition of  claim 38 , wherein the thermogram further comprises an endotherm corresponding to dehydration. 
     
     
         40 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 9 . 
     
     
         41 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 42 . 
     
     
         42 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 43 . 
     
     
         43 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a differential scanning calorimetry thermogram corresponding to the representative differential scanning calorimetry thermogram provided in  FIG. 44 . 
     
     
         44 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has between approximately 0.46 and approximately 0.59 moles of water per mole of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione. 
     
     
         45 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate that has a thermal gravimetric analysis curve comprising a weight loss of between about 3.1% and about 4.0% when heated from about 30° C. to about 175° C. 
     
     
         46 . 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 hemihydrate.   
     
     
         47 . 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 hemihydrate.   
     
     
         48 . 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 hemihydrate.   
     
     
         49 . 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 hemihydrate.