Solid state forms of spiro-oxindole compounds
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.
1. A crystalline form of funapide, designated as Form A 0 , characterized by one or more of the following: a powder X-ray diffraction pattern having peaks at 10.10°, 10.69°, 20.59°, 22.69° and 33.12° θ±0.2° θ; a powder X-ray diffraction pattern substantially as depicted in FIG. 1 ; and any combination of these data.
2. The crystalline form of claim 1 , characterized by a powder X-ray diffraction pattern having peaks at 10.10°, 10.69°, 20.59°, 22.69° and 33.12° θ±0.2° θ, further characterized by an additional one, two, three, four or five powder X-ray diffraction pattern peaks selected from 15.94°, 17.77°, 20.26°, 23.79°, and 30.84° θ±0.2° θ.
3. The crystalline form of funapide according to claim 1 or claim 2 , further characterized by one or more of the following: a DSC thermogram substantially as depicted in FIG. 2 ; an endothermic onset at 109° C. and a peak max at 114° 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 5 .
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 A 0 , wherein the method comprises one of the following methods to obtain the crystalline form of funapide designated as Form A 0 :
(a) equilibrating funapide at 25±3° C. with a mixture of solvents, filtering the resulting solutions; and drying the resulting solids;
(b) equilibrating funapide at 50° C. with a solvent or mixture of solvents, filtering the resulting solutions and drying the resulting solids;
(c) dissolving funapide in methyl tert-butyl ether at 22-25° C., cooling the resulting solution to 5° C., filtering the resulting solution and drying the resulting solids;
(d) dissolving funapide in a solvent or a mixture of solvents at 22-25° C., cooling the resulting solutions to 5° C., maintaining the temperature and allowing the solvent or mixture of solvents to slowly evaporate;
(e) mixing funapide with a mixture of solvents at 22-25° C., rapidly heating the resulting solutions to 50° C., maintaining the temperature and allowing the mixture of solvents to rapidly evaporate; and
(f) dissolving funapide in a first solvent, in which funapide is soluble, adding a second solvent, in which funapide is insoluble or poorly soluble, and filtering the resulting solutions.