Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses

Abstract

Solid forms comprising 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, compositions comprising the solid forms, methods of making the solid forms and methods of their uses are disclosed.

1 - 64 . (canceled) 
     
     
         65 . A method of treating or managing a disease or disorder selected from leukemia, lymphoma, myeloma, myelodysplastic syndrome, or myeloproliferative disease comprising administering to a patient having the disease or disorder a solid form of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione: 
       
         
           
           
               
               
           
         
         wherein the solid form has an X-ray powder diffraction pattern comprising: 
         peaks at approximately 14.6 °2θ, 15.6 °2θ, 16.7 °2θ, 21.9 °2θ and 30.0 °2θ as shown in  FIG. 1 ; 
         peaks at approximately 10.6 °2θ, 14.7 °2θ, 19.1 °2θ and 25.9 °2θ as shown in  FIG. 4 ; 
         peaks at approximately 10.8 °2θ, 15.1 °2θ, 25.1 °2θ and 26.6 °2θ as shown in  FIG. 7 ; 
         peaks at approximately 16.7 °2θ, 21.7 °2θ, 21.9 °2θ and 25.8 °2θ as shown in  FIG. 10 ; 
         peaks at approximately 7.3 °2θ, 14.6 °2θ, 22.0 °2θ, 30.0 °2θ and 37.0 °2θ as shown in  FIG. 13 ; or 
         peaks at approximately 14.5 °2θ, 15.7 °2θ, 22.7 °2θ and 29.9 °2θ as shown in  FIG. 16 . 
       
     
     
         66 . The method of  claim 65 , wherein disease or disorder is leukemia or lymphoma. 
     
     
         67 . The method of  claim 66 , wherein the lymphoma is Hodgkin's lymphoma. 
     
     
         68 . The method of  claim 66 , wherein the lymphoma is Non-Hodgkin's lymphoma. 
     
     
         69 . The method of  claim 68 , wherein the Non-Hodgkin's lymphoma is diffuse large B-cell lymphoma. 
     
     
         70 . The method of  claim 68 , wherein the Non-Hodgkin's lymphoma is cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, diffuse large B-cell lymphoma, Waldenstrom's macrogliobineima, mantle cell lymphoma, or follicular lymphoma. 
     
     
         71 . The method of  claim 65 , wherein the leukemia is chronic lymphocytic leukemia, chronic myelocytic leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, or acute myeloblastic leukemia. 
     
     
         72 . The method of  claim 65 , wherein the disease or disorder is multiple myeloma, smoldering myeloma, or indolent myeloma. 
     
     
         73 . The method of  claim 72 , wherein the disease or disorder is multiple myeloma. 
     
     
         74 . The method of  claim 72 , wherein the disease or disorder is refractory or resistant multiple myeloma. 
     
     
         75 . The method of  claim 66 , wherein the disease or disorder is myelodysplastic syndrome or myeloproliferative disease. 
     
     
         76 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 14.6 °2θ, 15.6 °2θ, 16.7 °2θ, 21.9 °2θ and 30.0 °2θ as shown in  FIG. 1 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         77 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 9.2 °2θ, 13.4 °2θ, 14.0 °2θ, 14.6 °2θ, 15.6 °2θ, 16.7 °2θ, 18.5 °2θ, 21.9 °2θ, 22.7 °2θ, 24.8 °2θ, 28.1 °2θ, 30.0 °2θ and 37.0 °2θ as shown in  FIG. 1 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         78 . The method of  claim 76 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 282° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         79 . The method of  claim 76 , wherein the solid form has a thermal gravimetric analysis plot comprising a mass loss of less than approximately 6% when heated from approximately 25° C. to approximately 150° C. 
     
     
         80 . The method of  claim 76 , wherein the solid form exhibits a mass increase of less than or equal to approximately 6% when subjected to an increase in relative humidity from approximately 0% to approximately 95% relative humidity. 
     
     
         81 . The method of claim Error! Reference source not found. 76 , wherein the solid form is hydrated. 
     
     
         82 . The method of  claim 81 , wherein the crystal lattice of the solid form comprises approximately one molar equivalent of water per mole of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione. 
     
     
         83 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 10.6 °2θ, 14.7 °2θ, 19.1 °2θ and 25.9 °2θ as shown in  FIG. 4 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         84 . The method of  claim 65  wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 10.6 °2θ, 11.4 °2θ, 12.6 °2θ, 13.7 °2θ, 14.7 °2θ, 19.1 °2θ, 20.3 °2θ, 20.9 °2θ, 21.2 °2θ, 22.9 °2θ, 24.9 °2θ, 25.3 °2θ, 25.9 °2θ, 26.9 °2θ, 29.5 °2θ and 33.8 °2θ as shown in  FIG. 4 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         85 . The method of  claim 83 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 279° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         86 . The method of  claim 83 , wherein the solid form has a thermal gravimetric analysis plot comprising a mass loss of less than approximately 0.1% when heated from approximately 25° C. to approximately 150° C. 
     
     
         87 . The method of  claim 83 , wherein the solid form exhibits a mass increase of less than approximately 0.2% when subjected to an increase in relative humidity from approximately 0% to approximately 95% relative humidity. 
     
     
         88 . The method of  claim 83 , wherein the solid form is unsolvated. 
     
     
         89 . The method of  claim 83 , wherein the solid form is substantially nonhygroscopic. 
     
     
         90 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 10.8 °2θ, 15.1 °2θ, 25.1 °2θ and 26.6 °2θ as shown in  FIG. 7 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         91 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 10.8 °2θ, 11.9 °2θ, 15.1 °2θ, 18.8 °2θ, 19.2 °2θ, 19.3 °2θ, 22.0 °2θ, 24.9 °2θ, 25.1 °2θ, 26.6 °2θ and 29.2 °2θ as shown in  FIG. 7 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         92 . The method of  claim 90 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 281° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         93 . The method of  claim 90 , wherein the solid form has a thermal gravimetric analysis plot comprising a mass loss of less than approximately 0.1% when heated from approximately 25° C. to approximately 150° C. 
     
     
         94 . The method of  claim 90 , wherein the solid form exhibits a mass increase of less than approximately 0.2% when subjected to an increase in relative humidity from approximately 0% to approximately 95% relative humidity. 
     
     
         95 . The method of  claim 90 , wherein the solid form is unsolvated. 
     
     
         96 . The method of  claim 90 , wherein the solid form is substantially nonhygroscopic. 
     
     
         97 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 16.7 °2θ, 21.7 °2θ, 21.9 °2θ and 25.8 °2θ as shown in  FIG. 10 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         98 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 10.6 °2θ, 14.0 °2θ, 14.6 °2θ, 15.7 °2θ, 16.3 °2θ, 16.7 °2θ, 18.8 °2θ, 21.7 °2θ, 21.9 °2θ, 24.8 °2θ, 25.1 °2θ, 25.8 °2θ, 28.1 °2θ and 28.6 °2θ as shown in  FIG. 10 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         99 . The method of  claim 97 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 283° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         100 . The method of  claim 97 , wherein the solid form has a thermal gravimetric analysis plot comprising a mass loss of less than approximately 4% when heated from approximately 25° C. to approximately 150° C. 
     
     
         101 . The method of  claim 97 , wherein the solid form exhibits a mass increase of less than or equal to approximately 6% when subjected to an increase in relative humidity from approximately 0% to approximately 95% relative humidity. 
     
     
         102 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 7.3 °2θ, 14.6 °2θ, 22.0 °2θ, 30.0 °2θ and 37.0 °2θ as shown in  FIG. 13 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         103 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 7.3 °2θ, 9.3 °2θ, 12.2 °2θ, 14.0 °2θ, 14.6 °2θ, 15.7 °2θ, 16.8 °2θ, 21.0 °2θ, 22.0 °2θ, 22.7 °2θ, 29.4 °2θ, 30.0 °2θ and 37.0 °2θ as shown in  FIG. 13 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         104 . The method of  claim 102 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 279° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         105 . The method of  claim 102 , wherein the solid form has a thermal gravimetric analysis plot comprising a mass loss of less than approximately 6% when heated from approximately 25° C. to approximately 150° C. 
     
     
         106 . The method of  claim 102 , wherein the solid form exhibits a mass increase of less than approximately 0.5% when subjected to an increase in relative humidity from approximately 0% to approximately 95% relative humidity. 
     
     
         107 . The method of  claim 102 , wherein the solid form is hydrated. 
     
     
         108 . The method of  claim 102 , wherein the solid form is substantially nonhygroscopic. 
     
     
         109 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 14.5 °2θ, 15.7 °2θ, 22.7 °2θ and 29.9 °2θ as shown in  FIG. 16 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         110 . The method of  claim 65 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks at approximately 7.2 °2θ, 9.1 °2θ, 14.5 °2θ, 15.7 °2θ, 16.8 °2θ, 18.3 °2θ, 21.9 °2θ, 22.7 °2θ, 29.9 °2θ and 36.9 °2θ as shown in  FIG. 16 , when analyzed using Cu Kα X-ray radiation at 1.54 Å. 
     
     
         111 . The method of  claim 109 , wherein the solid form has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of approximately 267° C., when heated from approximately 25° C. to approximately 300° C. 
     
     
         112 . The method of  claim 109 , wherein the solid form is hydrated. 
     
     
         113 . The method of  claim 65 , wherein two or more of the solid forms are administered. 
     
     
         114 . The method of  claim 65 , wherein the solid form is administered at a dose of about 1 mg to about 20 mg. 
     
     
         115 . The method of  claim 65 , wherein a pharmaceutical composition comprising the solid form and a pharmaceutical acceptable carrier, diluent or excipient is administered. 
     
     
         116 . The method of  claim 115 , wherein the composition is formulated for oral, parenteral, or intravenous administration. 
     
     
         117 . The method of  claim 115 , wherein the composition is formulated as a single unit dosage form. 
     
     
         118 . The method of  claim 117 , wherein the dosage form is a tablet or capsule. 
     
     
         119 . The method of  claim 65 , further comprising administering a second active agent.