Claims
- 1. Fexofenadine base Form I.
- 2. A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 9.8, 11.6, 12.1, 13.5, 14.0, 18.0, 18.4 and 19.7±0.2 degrees two theta.
- 3. The fexofenadine base of claim 2 having a PXRD pattern substantially as depicted in FIG. 1.
- 4. A fexofenadine base in a crystalline form having a differential scanning calorimetric thermogram with an endothermic peak at about 100° C. and an endothermic peak at about 143° C., and two exothermic peaks at about 155° C. and about 180° C.
- 5. A process for preparing fexofenadine base having at least one of characteristics of Form I comprising the steps of:
a) preparing a solution of fexofenadine base in 1-propanol; b) admixing the solution with water, ice or a mixture thereof to precipitate fexofenadine base; and c) separating the precipitate.
- 6. The fexofenadine base prepared by the process of claim 5.
- 7. Fexofenadine base Form II.
- 8. A fexofenadine base in a crystalline form having a PXRD pattern with peaks at about 7.4, 9.7, 11.7, 12.1, 13.8, 14.4, 18.0, 18.5 and 19.7±0.2 degrees two theta.
- 9. The fexofenadine base of claim 8 having a powder PXRD pattern substantially as depicted in FIG. 3.
- 10. A fexofenadine base in a crystalline form having a differential scanning calorimetric thermogram with an endotherm at about 100° C., a maximum endotherm at about 223° C. and a minor endotherm at about 144° C., and two exotherms at about 146° C. and about 182° C.
- 11. A process for preparing fexofenadine base having at least one of characteristics of Form II comprising the steps of:
a) preparing a solution of fexofenadine base in a mixture of water and 1-propanol, wherein fexofenadine base precipitates from the solution; and b) separating the fexofenadine base.
- 12. The process of claim 11, wherein the mixture is from about a 1:1 to about a 4:1 mixture (vol/vol) of water and 1-propanol.
- 13. The process of claim 12, wherein the mixture is about a 3:1 mixture of water and 1-propanol.
- 14. The fexofenadine base prepared by the process of claim 11.
- 15. Fexofenadine base Form III.
- 16. A fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 4.4, 10.3, 11.3, 16.3, 19.8±0.2 degrees 2θ.
- 17. The fexofenadine base of claim 16 having a PXRD pattern as substantially depicted in FIG. 5.
- 18. A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm followed by an exotherm at about 200° C., and an additional endotherm at about 226° C.
- 19. The fexofenadine base of claim 18 characterized by a DSC thermogram with two exothermic peaks at about 107° C. and about 166° C., and an endotherm at about 226° C.
- 20. A process for preparing fexofenadine base having at least one of characteristics of Form III comprising the steps of:
a) slurrying fexofenadine base in methanol; b) heating the slurry; and c) separating fexofenadine base Form III as a solid.
- 21. The fexofenadine base prepared by the process of claim 20
- 22. The process of claim 20, wherein heating involves a temperature of from about 45° C. to about reflux.
- 23. The process of claim 20, wherein the fexofenadine base used in step (a) is not fexofenadine base Form IV.
- 24. Fexofenadine base Form IV.
- 25. Fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 4.3, 8.7, 12.5, 13.1 and 13.6±0.2 degrees 2θ.
- 26. The fexofenadine base of claim 25, further characterized by peaks at about 16.3, 16.7, 17.5, 18.1, 18.5, 19.6, 20.7, 21.8 and 22.6±0.2 degrees 2θ.
- 27. A process for preparing fexofenadine base having one of characteristics of Form IV comprising the steps of:
a) preparing a solution of fexofenadine base in a mixture of a C1 to a C4 alcohol and water, with the proviso that the alcohol is not 1-propanol, wherein fexofenadine base precipitates from the solution; and b) separating the precipitate.
- 28. The process of claim 27, wherein the alcohol is methanol.
- 29. The process of claim 27 or 28, wherein preparing a solution involves preparing a first solution of a sodium or potassium salt of fexofenadine followed by acidification of the first solution.
- 30. A process for preparing fexofenadine base having one of characteristics of Form IV comprising the steps of:
a) preparing a solution of a sodium or a potassium salt of fexofenadine in a mixture of a C1 to a C4 alcohol and water, with the proviso that the alcohol is not 1-propanol; and b) acidifying the solution to precipitate fexofenadine base.
- 31. The process of claim 30, wherein the alcohol is methanol.
- 32. The process of claim 30 or 31, wherein the solution has a pH of more than about 8.
- 33. The process of claim 30 or 31, wherein acidifying results in a pH of from about 4 to about 7.
- 34. The fexofenadine base prepared by the process of claim 27 or 30.
- 35. Fexofenadine base Form V.
- 36. A fexofenadine base in a crystalline form characterized by a PXRD diffraction pattern with peaks at about 17.2, 18.2, 18.8, 20.3±0.2 degrees 2θ.
- 37. The fexofenadine base of claim 36 further characterized by a PXRD pattern with peaks at about 13.2, 13.7, 14.4±0.2 degrees 2θ.
- 38. The fexofenadine base of claim 37 further characterized by a PXRD pattern as substantially depicted in FIG. 7.
- 39. A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm followed by an exotherm at about 200° C., and an additional endotherm at about 226° C.
- 40. A process for preparing fexofenadine base having at least one of characteristics of Form V comprising the steps of:
a) slurrying fexofenadine base in methyl ethyl ketone; and b) separating fexofenadine base Form V as a solid.
- 41. The fexofenadine base prepared by the process of claim 40.
- 42. Fexofenadine base Form VI.
- 43. A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 3.9, 9.6, 11.8, 16.0 and 19.0±0.2 degrees 2θ.
- 44. The fexofenadine base of claim 43 further characterized by a PXRD pattern as substantially depicted in FIG. 9.
- 45. A fexofenadine base in a crystalline form characterized by a DSC thermogram with endotherms at about 140° C. and about 229° C., and an exotherm at about 160° C.
- 46. A process for preparing fexofenadine base having at least one of characteristics of Form VI comprising the steps of:
a) slurrying fexofenadine base in methanol under suitable condition; and b) separating fexofenadine base Form VI as a solid.
- 47. The process of claim 46, further comprising repeating steps (a) and (b) at least once.
- 48. The process of claim 46, wherein step (a) is carried out at a temperature of about 30° C. or below.
- 49. The process of claim 46, wherein the fexofenadine base used in step (a) is not fexofenadine base Form IV.
- 50. A Fexofenadine base Form VII.
- 51. A fexofenadine base in a crystalline form characterized by a PXRD pattern with peaks at about 3.9, 7.7, 10.6, 13.4, 14.5 and 19.2±0.2 degrees 2θ.
- 52. The fexofenadine base of claim 50 further characterized by a PXRD pattern as substantially depicted in FIG. 11.
- 53. A fexofenadine base in a crystalline form characterized by a DSC thermogram with an endotherm at about 228° C.
- 54. A process for preparing fexofenadine base having at least one of characteristics of Form VII comprising carrying out an azeotropic distillation of fexofenadine base in toluene to remove water.
- 55. The process of claim 54, further comprising recrystallizing the fexofenadine base from methanol.
- 56. A pharmaceutical composition comprising an effective amount of fexofenadine selected from the group consisting of base Forms I, II, III, IV, V, VI and VII, and a pharmaceutically acceptable excipient.
- 57. A method of inhibiting binding between an H1 receptor and histamine in a patient suffering from contraction of the bronchi, vasodilation, itching or other inflammation response to histamine comprising administering to the patient the pharmaceutical composition of claim 56.
- 58. A method of alleviating symptoms of allergic rhinitis in a patient susceptible to allergic rhinitis or experiencing symptoms of allergic rhinitis comprising administering to the patient the pharmaceutical composition of claim 56.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. §119(e) of provisional applications Serial Nos. 60/336,930, filed Nov. 8, 2001; 60/339,041, filed Dec. 7, 2001; 60/344,114, filed Dec. 28, 2001; 60/361,780, filed Mar. 4, 2002; 60/363,482, filed Mar. 11, 2002; 60/387,670, filed Jun. 10, 2002; 60/390,198, filed Jun. 19, 2002, 60/403,765, filed Aug. 15, 2002; 60/406,214, filed Aug. 27, 2002 and claims the benefit under 35 U.S.C. §120 of U.S. patent application Ser. No. 10/133,460, filed Apr. 26, 2002, which is in turn a continuation-in-part of U.S. patent application Ser. No. 10/118,807, filed Apr. 8, 2002, all of which are incorporated herein by reference.
Provisional Applications (9)
|
Number |
Date |
Country |
|
60336930 |
Nov 2001 |
US |
|
60339041 |
Dec 2001 |
US |
|
60344114 |
Dec 2001 |
US |
|
60361780 |
Mar 2002 |
US |
|
60363482 |
Mar 2002 |
US |
|
60387670 |
Jun 2002 |
US |
|
60390198 |
Jun 2002 |
US |
|
60403765 |
Aug 2002 |
US |
|
60406214 |
Aug 2002 |
US |