Patent EA-003464-B1 (EA)
Title: Polymorphic crystalline forms of celecoxib
Inventor: FERRO LEONARD J
IPC: A61K9/24
Filed: 2000-12-01
Abstract: 1. A Form I crystalline form of celecoxib. 2. The crystalline form of Claim 1 having an X-ray powder diffraction pattern with peaks at about 5.5, 5.7, 7.2, or 16.6 degrees two theta. 3. The crystalline form of Claim 1 having an X-ray powder diffraction pattern substantially as shown in the top trace in Figure 1a. 4. The crystalline form of Claim 1 having a melting range from about 160 degree C to about 164 degree C. 5. The crystalline form of Claim 1 having a melting range from about 162 degree C to about 163 degree C. 6. The crystalline form of Claim 5 having a melting point of about 162.8 degree C. 7. The crystalline form of Claim 5 having a differential scanning calorimetry endotherm maximum from about 160.0 degree C to about 164.0 degree C 8. The crystalline form of Claim 5 having an endotherm maximum at about 163.3 degree C. 9. The crystalline form of Claim 8 further having a melting range from about 160 degree C to about 164 degree C. 10. The crystalline form of Claim 9 having a melting point of about 162.8 degree . 11. The crystalline form of Claim 1 having an Infrared Spectrum which has a peak at about 3250 to about 3260 cm<-1>. 12. The crystalline form of Claim 11 having an Infrared Spectrum which has a peak at about 3256 cm<-1>. 13. The crystalline form of Claim 1 having an Infrared Spectrum which has a peak at about 3350 to about 3360 cm<-1>. 14. The crystalline form of Claim 13 having an Infrared Spectrum which has a peak at about 3356 cm<-1>. 15. The crystalline form of Claim 1 having an Infrared Spectrum which has peaks at about 3256 cm<-1> and about 3356 cm<-1>, and having a melting point of about 162.8 degree C. 16. The crystalline form of Claim 1 having a phase purity of at least about 5% Form I celecoxib. 17. The crystalline form of Claim 1 having a phase purity of at least about 10% Form I celecoxib. 18. The crystalline form of Claim 1 having a phase purity of at least about 25% Form I celecoxib. 19. The crystalline form of Claim 1 having a phase purity of at least about 50% Form I celecoxib. 20. The crystalline form of Claim 1 having a phase purity of at least about 75% Form I celecoxib. 21. The crystalline form of Claim 1 having a phase purity of at least about 90% Form I celecoxib. 22. The crystalline form of Claim 1 having a substantially pure form of Form I celecoxib. 23. A pharmaceutical composition comprising a therapeutically-effective amount of the crystalline form of any one of Claims 2 to 22 and at least one pharmaceutically-acceptable carrier, adjuvant or diluent. 24. The composition of Claim 23 wherein the celecoxib comprises at least 2% Form I celecoxib. 25. The composition of Claim 23 wherein the celecoxib comprises at least 10% Form I celecoxib. 26. The composition of Claim 23 wherein the celecoxib comprises at least 50% Form I celecoxib. 27. The composition of Claim 23 wherein the celecoxib comprises at least 98% Form I celecoxib. 28. The composition of Claim 23 wherein the celecoxib is predominantly Form I celecoxib. 29. A method of treating or preventing a cyclooxygenase-2-mediated condition or disorder in a subject, said method comprising administering to the subject a therapeutically-effective amount of Form I celecoxib. 30. The method of Claim 29 wherein the condition or disorder is pain. 31. The method of Claim 29 wherein the condition or disorder is inflammation. 32. The method of Claim 29 wherein the condition or disorder is arthritis. 33. The method of Claim 29 wherein the condition or disorder is tumor growth. 34. The method of Claim 29 wherein the condition or disorder is metastasis. 35. The method of Claim 29 wherein the condition or disorder is familial adenomatous polyposis. 36. A method of preparing Form I celecoxib comprising crystallizing celecoxib from a mixture comprising celecoxib and a solvent, wherein the crystallization is performed at a temperature above the enantiotropic transition temperature of Form I celecoxib thereby producing Form I celecoxib. 37. The method of Claim 36 further comprising seeding the solvent with a seed crystal of Form I celecoxib prior to the crystallization. 38. The method of Claim 36 wherein the Form I celecoxib thereby produced has at least about 5 weight percent phase purity. 39. The method of Claim 36 wherein the Form I celecoxib thereby produced has at least about 10 weight percent phase purity. 40. The method of Claim 36 wherein the Form I celecoxib thereby produced has at least about 50 weight percent phase purity. 41. The method of Claim 36 wherein the Form I celecoxib thereby produced has at least about 90 weight percent phase purity. 42. The method of Claim 36 wherein the Form I celecoxib thereby produced has at least about 25 weight percent phase purity. 43. A method of preparing a crystalline form of celecoxib wherein the method comprises heating a solvate of celecoxib thereby producing Form I celecoxib. 44. The method of Claim 43 in which the solvate is heated to a temperature of about 50 degree C to about 160 degree C. 45. The method of Claim 43 in which the solvate is heated to a temperature of about 60 degree C to about 150 degree C. 46. The method of Claim 43 in which the solvate is heated to a temperature of about 70 degree C to about 140 degree C. 47. The method of Claim 43 in which the solvate is heated to a temperature of about 80 degree C to about 130 degree C. 48. The method of Claim 43 in which the solvate is heated to a temperature of about 85 degree C to about 12 0 degree C. 49. The method of Claim 43 in which the solvate is heated to a temperature of about 90 degree C to about 110 degree C. 50. The method of Claim 43 in which the solvate is heated to a temperature of about 100 degree C. 51. The method of Claim 43 wherein the solvate is heated for more than about 1 minute. 52. The method of Claim 43 wherein the solvate is heated for more than about 5 minutes. 53. The method of Claim 43 wherein the solvate is heated for more than about 60 minutes. 54. The method of Claim 43 wherein the solvate is heated for more than about 2 hours. 55. The method of Claim 43 wherein the solvate is heated for about 4 hours or longer. 56. The method of any one of Claims 43-55 wherein the heating is performed below atmospheric pressure. 57. The method of Claim 56 wherein the solvate of celecoxib comprises celecoxib and an amide solvent. 58. The method of Claim 57 wherein the amide solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2- pyrrolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and 1,1,3,3-tetramethylurea. 59. The method of Claim 58, wherein the amide solvent is N,N-dimethylformamide. 60. The method of Claim 58, wherein the amide solvent is N,N-dimethylacetamide. 61. The method of Claim 58, wherein the amide solvent is 1-methyl-2-pyrrolidinone. 62. The method of Claim 58, wherein the amide solvent is 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. 63. The method of Claim 58, wherein the amide solvent is 1,1,3,3-tetramethylurea. 64. The method of Claim 58 wherein the solvate of celecoxib is prepared by a process comprising mixing celecoxib with an amide solvent selected from a group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidinone, 1,3dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and 1,1,3,3-tetramethylurea. 65. The method according to Claim 64 wherein the amide solvent is N,N-dimethylformamide. 66. The method according to Claim 64 wherein the amide solvent is, N,N-dimethylacetamide. 67. The method according to Claim 64 wherein the amide solvent is 1-methyl-2-pyrrolidinone. 68. The method according to Claim 64 wherein the amide solvent is 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. 69. The method according to Claim 64 wherein the amide solvent is 1,1,3,3-tetramethylurea. 70. A method of producing Form I celecoxib wherein the method comprises milling or grinding Form III celecoxib thereby producing Form I celecoxib. 71. The method of Claim 70 comprising milling Form III celecoxib. 72. The method of Claim 71 wherein the milling is wet milling. 73. The method of Claim 71 wherein the milling is ball milling. 74. The method of Claim 70 comprising grinding Form III celecoxib. 75. The method of Claim 74 wherein the grinding is performed by shaking. 76. A method of producing Form I celecoxib wherein the method comprises milling or grinding a celecoxib solvate thereby producing Form I celecoxib. 77. The method of Claim 76 comprising milling a celecoxib solvate. 78. The method of Claim 77 wherein the milling is wet milling. 79. The method of Claim 77 wherein the milling is ball milling. 80. The method of Claim 76 comprising grinding a celecoxib solvate. 81. The method of Claim 80 wherein the grinding is performed by shaking. 82. A method of producing Form I celecoxib wherein the method comprises melting Form II celecoxib and cooling the melt thereby producing Form I celecoxib. 83. A method of producing Form I celecoxib wherein the method comprises melting Form III celecoxib and cooling the melt thereby producing Form I celecoxib. 84. A method of producing Form I celecoxib wherein the method comprises evaporating solvent from a celecoxib solution thereby producing Form I celecoxib. 85. The method of Claim 84 wherein the solvent is selected from the group consisting of an ether and a hydrocarbon. 86. The method of Claim 84 wherein the solvent comprises an ether and a hydrocarbon. 87. The method of Claim 86 wherein the solvent comprises ethyl acetate and heptane. 88. The method of Claim 87 wherein the ethyl acetate and the heptane are at a ratio of about 15:85. 89. The method of Claim 84 wherein the evaporation is performed below atmospheric pressure. 90. The method of Claim 84 wherein the evaporation is performed at a temperature of about 35 degree C. 91. A Form II crystalline form of celecoxib. 92. The crystalline form of Claim 91 having an X-ray powder diffraction pattern with a peak at about 10.3, 13.8 or 17.7