Solid state forms of spiro-oxindole compounds

Abstract

The present invention provides solid state forms of certain spiro-oxindole compounds, such as funapide and the racemic mixture of funapide and its corresponding (R) enantiomer, pharmaceutical compositions comprising the solid state forms and processes for preparing the solid state forms and the pharmaceutical compositions.

What is claimed is: 
     
         1 . A crystalline form of funapide, designated as Form B 0 , characterized by one or more of the following: a powder X-ray diffraction pattern having peaks at 9.61°, 10.03°, 14.95°, 19.28°, and 21.30° θ±0.2° θ; a powder X-ray diffraction pattern substantially as depicted in  FIG. 5 ; and any combination of these data. 
     
     
         2 . The crystalline form of funapide of  claim 1 , characterized by a powder X-ray diffraction pattern having peaks at 9.61°, 10.03°, 14.95°, 19.28°, and 21.30° θ±0.2° θ, further characterized by an additional one, two, three, four or five powder X-ray diffraction pattern peaks selected from 12.51°, 16.14°, 18.03°, 18.72°, and 25.50° θ±0.2° θ. 
     
     
         3 . The crystalline form funapide of  claim 1  or  2 , further characterized by one or more of the following: a DSC thermogram substantially as depicted in  FIG. 6 ; an endothermic onset at 103° C. and a peak max at 105° C., or combinations thereof. 
     
     
         4 . A pharmaceutical composition comprising the crystalline form of funapide according to  claim 1 . 
     
     
         5 . A pharmaceutical formulation comprising the crystalline form of funapide according  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
         6 . A pharmaceutical formulation comprising the pharmaceutical composition of  claim 4  and at least one pharmaceutically acceptable excipient. 
     
     
         7 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, wherein the method comprises administering to the subject a pharmaceutical composition according to  claim 4 . 
     
     
         8 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, wherein the method comprises administering to the subject the pharmaceutical formulation according to  claim 7 . 
     
     
         9 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, comprising administering to the subject a therapeutically effective amount of the crystalline form of funapide according to  claim 1 . 
     
     
         10 . A method of preparing a pharmaceutical composition comprising combining the crystalline form of funapide according to  claim 1  with a one or more pharmaceutically acceptable excipients. 
     
     
         11 . A method of preparing a crystalline form of funapide designated as Form B 0 . 
     
     
         12 . A crystalline form of the racemic mixture of funapide and its corresponding (R)-enantiomer, characterized by one or more of the following: X-ray powder diffraction pattern having peaks at 13.68°, 14.83°, 20.17°, 25.49° and 29.80° θ±0.2° θ; an X-ray powder diffraction pattern as depicted in  FIG. 11 ; and combinations of these data. 
     
     
         13 . A pharmaceutical composition comprising the crystalline form of the racemic mixture of funapide and its corresponding (R)-enantiomer of  claim 12 . 
     
     
         14 . A pharmaceutical formulation comprising the crystalline form of a racemic mixture of funapide and its corresponding (R)-enantiomer of  claim 12 , and at least one pharmaceutically acceptable excipient. 
     
     
         15 . A pharmaceutical formulation comprising the pharmaceutical composition of  claim 13  and at least one pharmaceutically acceptable excipient. 
     
     
         16 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, wherein the method comprises administering to the subject a pharmaceutical composition of  claim 13 . 
     
     
         17 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, wherein the method comprises administering to the subject the pharmaceutical formulation of  claim 14 . 
     
     
         18 . A method of treating a subject suffering from sodium channel-mediated diseases and conditions, comprising administering to the subject a therapeutically effective amount of the crystalline form of a racemic mixture of funapide and its corresponding (R)-enantiomer of  claim 12 . 
     
     
         19 . A method of preparing a pharmaceutical composition comprising combining the crystalline form of a racemic mixture of funapide and its corresponding (R)-enantiomer of  claim 12 , with a one or more pharmaceutically acceptable excipients. 
     
     
         20 . A method of preparing the crystalline form of the racemic mixture of funapide and its corresponding (R)-enantiomer of  claim 12 . 
     
     
         21 . An amorphous form of funapide characterized by X-ray powder diffraction pattern as depicted in  FIG. 9  and by a DSC thermograph as depicted in  FIG. 10  showing a glass transition at 42° C. and crystallization at 72° C. 
     
     
         22 . A method of preparing an amorphous form of funapide as described herein.