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:
 a) amorphous 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione; and   b) crystalline 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.   
     
     
         30 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative differential scanning calorimetry thermogram provided in  FIG. 4 . 
     
     
         31 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative thermal gravimetric analysis curve provided in  FIG. 4 . 
     
     
         32 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative infrared spectrum provided in  FIG. 2 . 
     
     
         33 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative Raman spectrum provided in  FIG. 3 . 
     
     
         34 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that does not exhibit a significant weight gain from 5% to 95% relative humidity. 
     
     
         35 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative moisture sorption/desorption isotherm provided in  FIG. 5 . 
     
     
         36 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the solubility curve provided in  FIG. 51 . 
     
     
         37 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that corresponds to the representative X-ray powder diffraction pattern provided in  FIG. 1 . 
     
     
         38 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that has a differential scanning calorimetry thermogram having an endotherm at approximately 270° C. 
     
     
         39 . The composition of  claim 29 , comprising crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione that has a thermogravimetric analysis curve indicative of an unsolvated material. 
     
     
         40 . 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 having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ.   
     
     
         41 . 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 having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ.   
     
     
         42 . 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- having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ.   
     
     
         43 . 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 having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ.