Crystal forms

Abstract

The present invention features crystalline forms of Compound I. In one embodiment, a crystalline form of Compound I has characteristic peaks in the PXRD pattern as shown in one of FIGS. 1-10.

What is claimed is: 
     
       1. A process for making a pharmaceutical composition comprising Compound I 
       
         
           
           
               
               
           
         
         comprising dissolving combining a crystalline form of Compound I in a solvent with a hydrophilic polymer, wherein said crystalline form has characteristic peaks in PXRD pattern as described in one of Tables 1-10 when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å wherein the crystalline form has a powder X-ray diffraction pattern comprising a two theta (° 2θ) peak at about 17.62±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å. 
       
     
     
       2. The process of  claim 1 , wherein said solvent is a volatile solvent, and said the process further comprises dissolving Compound I and the polymer in a solvent, and spray drying the dissolved Compound I resulting solution to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I and the polymer. 
     
     
       3. The process of  claim 1 , wherein said solvent the polymer is a molten or rubbery polymer in which the crystalline form of Compound I dissolves, and said the process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and said polymer the polymer. 
     
     
       4. The process of  claim 1 , wherein said characteristic peaks in PXRD pattern are as described in Table 9. 
     
     
       5. The process of  claim 2 , wherein said characteristic peaks in PXRD pattern are as described in Table 9. 
     
     
       6. The process of  claim 3 , wherein said characteristic peaks in PXRD pattern are as described in Table 9. 
     
     
       7. A process for making a pharmaceutical composition comprising Compound I, 
       
         
           
           
               
               
           
         
       
       comprising dissolving a crystalline form of Compound I in a solvent, wherein said crystalline form has characteristic peaks in PXRD pattern as described in one of  FIGS. 1-10  when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å. 
     
     
       8. The process of  claim 7 , wherein said solvent is a volatile solvent, and said process further comprises spray drying the dissolved Compound I to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I. 
     
     
       9. The process of  claim 7 , wherein said solvent is a molten or rubbery polymer, and said process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and said polymer. 
     
     
       10. The process of  claim 7 , wherein said characteristic peaks in PXRD pattern are as described in  FIG. 9 . 
     
     
       11. The process of  claim 8 , wherein said characteristic peaks in PXRD pattern are as described in  FIG. 9 . 
     
     
       12. The process of  claim 9 , wherein said characteristic peaks in PXRD pattern are as described in  FIG. 9 . 
     
     
       13. A process for making a pharmaceutical composition comprising Compound I, 
       
         
           
           
               
               
           
         
       
       comprising dissolving a crystalline form of Compound I in a solvent, wherein said crystalline form has characteristic peaks in PXRD pattern at values of two theta (° 2θ) of 5.31, 11.11, 12.60, 13.75, 15.29, 15.96, 17.62, 19.71, 21.30, and 22.88 when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å. 
     
     
       14. The process of  claim 13 , wherein said solvent is a volatile solvent, and said process further comprises spray drying the dissolved Compound I to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I. 
     
     
       15. The process of  claim 13 , wherein said solvent is a molten or rubbery polymer, and said process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and said polymer. 
     
     
       16. A process for making a pharmaceutical composition comprising Compound I, 
       
         
           
           
               
               
           
         
       
       comprising dissolving a crystalline form of Compound I in a solvent, wherein said crystalline form has characteristic peaks in PXRD pattern at values of two theta (° 2θ) of 5.31, 10.16, 10.62, 11.11, 12.60, 13.75, 15.29, 15.96, 17.62, 18.19, 19.16, 19.71, 20.58, 21.30, 22.40, 22.88, 23.66, 26.40, 26.74, and 33.46 when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å. 
     
     
       17. The process of  claim 16 , wherein said solvent is a volatile solvent, and said process further comprises spray drying the dissolved Compound I to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I. 
     
     
       18. The process of  claim 16 , wherein said solvent is a molten or rubbery polymer, and said process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and said polymer. 
     
     
       19. A process for making a pharmaceutical composition comprising Compound I, 
       
         
           
           
               
               
           
         
       
       comprising dissolving a crystalline form of Compound I in a solvent, wherein said crystalline form has characteristic peaks in PXRD pattern at values of two theta (° 2θ) of 5.31, 10.16, 10.62, 11.11, 12.60, 13.75, 15.29, 15.96, 17.62, 18.19, 19.16, 19.71, 20.58, 21.30, 22.40, 22.88, 23.66, 26.40, 26.74, 28.12, 31.62, and 33.46 when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å. 
     
     
       20. The process of  claim 19 , wherein said solvent is a volatile solvent, and said process further comprises spray drying the dissolved Compound I to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I. 
     
     
       21. The process of  claim 19 , wherein said solvent is a molten or rubbery polymer, and said process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and said polymer. 
     
     
       22. The process of claim 1, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 13.75±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       23. The process of claim 22 wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 11.11±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       24. A process for making a pharmaceutical composition comprising Compound I 
       
         
           
           
               
               
           
         
         comprising combining a crystalline form of Compound I with a hydrophilic polymer wherein the crystalline form has a powder X-ray diffraction pattern comprising a two theta (° 2θ) peak at about 10.16±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å, wherein the crystalline form is anhydrous.  
       
     
     
       25. The process of claim 24 wherein the process further comprises dissolving Compound I and the polymer in a solvent, and spray drying the resulting solution to remove the solvent, thereby creating a solid dispersion comprising amorphous Compound I and the polymer.  
     
     
       26. The process of claim 24, wherein the polymer is a molten or rubbery polymer in which the crystalline form of Compound I dissolves, and the process further comprises cooling and solidifying the dissolved Compound I, thereby creating a solid dispersion comprising amorphous Compound I and the polymer.  
     
     
       27. The process of claim 24, wherein the crystalline form is anhydrous.  
     
     
       28. The process of claim 24, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 21.30±0.2° 2θ and about 23.66±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       29. The process of claim 24, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 5.31±0.2° 2θ, 11.11±0.2° 2θ, 12.60±0.2° 2θ, 13.75±0.2° 2θ, 15.29±0.2° 2θ, 15.96±0.2° 2θ, 19.71±0.2° 2θ, 21.30±0.2° 2θ, and 22.88±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       30. The process of claim 24, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 5.31±0.2° 2θ, 10.62±0.2° 2θ, 11.11±0.2° 2θ, 12.60±0.2° 2θ, 13.75±0.2° 2θ, 15.29±0.2° 2θ, 15.96±0.2° 2θ, 17.62±0.2° 2θ, 18.19±0.2° 2θ, 19.16±0.2° 2θ, 19.71±0.2° 2θ, 20.58±0.2°2θ, 21.30±0.2° 2θ, 22.40±0.2° 2θ, 22.88±0.2° 2θ, 23.66±0.2° 2θ, 26.40±0.2° 2θ, 26.74±0.2° 2θ and 33.46±0.2° 2θ, when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       31. The process of claim 24, wherein the crystalline form has a powder X-ray diffraction pattern of Pattern G.  
     
     
       32. A crystalline form of Compound I, 
       
         
           
           
               
               
           
         
         wherein the crystalline form has a powder X-ray diffraction pattern comprising a two theta (° 2θ) peak at about 17.62±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
       
     
     
       33. The crystalline form of claim 32, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 13.75±0.2° 2θ.  
     
     
       34. The crystalline form of claim 33, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 11.11±0.2° 2θ.  
     
     
       35. A crystalline form of Compound I, 
       
         
           
           
               
               
           
         
         wherein the crystalline form has a powder X-ray diffraction pattern comprising a two theta (° 2θ) peak at about 10.16±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
       
     
     
       36. The process of claim 35, wherein the crystalline form is anhydrous.  
     
     
       37. The crystalline form of claim 35, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 21.30±0.2° 2θ and about 23.66±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       38. The crystalline form of claim 35, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 5.31±0.2° 2θ, 11.11±0.2° 2θ, 12.60±0.2° 2θ, 13.75±0.2° 2θ, 15.29±0.2° 2θ, 15.96±0.2° 2θ, 19.71±0.2° 2θ, 21.30±0.2° 2θ, and 22.88±0.2° 2θ when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       39. The crystalline form of claim 35, wherein the crystalline form has a powder X-ray diffraction pattern further comprising a two theta (° 2θ) peak at about 5.31±0.2° 2θ, 10.62±0.2° 2θ, 11.11±0.2° 2θ, 12.60±0.2° 2θ, 13.75±0.2° 2θ, 15.29±0.2° 2θ, 15.96±0.2° 2θ, 17.62±0.2° 2θ, 18.19±0.2° 2θ, 19.16±0.2° 2θ, 19.71±0.2° 2θ, 20.58±0.2° 2θ, 21.30±0.2° 2θ, 22.40±0.2° 2θ, 22.88±0.2° 2θ, 23.66±0.2° 2θ, 26.40±0.2° 2θ, 26.74±0.2° 2θ and 33.46±0.2° 2θ, when tested using a diffractometer that is operated with a copper anode tube at 40 kV and 30 mA and a germanium monochromator to provide monochromatic Cu-K α  radiation with a wavelength of 1.54178 Å.  
     
     
       40. The crystalline form of claim 35, wherein the crystalline form has a powder X-ray diffraction pattern of Pattern G.