Claims
- 1. An oral fast-melt composition comprising
(a) particulate valdecoxib in a therapeutically effective amount, (b) at least one pharmaceutically acceptable dissolution retardant, and (c) at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution; wherein the composition is organoleptically acceptable.
- 2. The composition of claim 1 which, when placed in United States Pharmacopeia 24 in vitro disintegration Test Number 701, exhibits a disintegration time of less than about 300 seconds.
- 3. The composition of claim 1 which, when placed in United States Pharmacopeia 24 in vitro disintegration Test Number 701, exhibits a disintegration time of less than about 200 seconds.
- 4. The composition of claim 1 which, when placed in United States Pharmacopeia 24 in vitro disintegration Test Number 701, exhibits a disintegration time of less than about 100 seconds.
- 5. The composition of claim 1 which disintegrates within about 60 seconds after placement in the oral cavity of a human subject.
- 6. The composition of claim 1 which disintegrates within about 30 seconds after placement in the oral cavity of a human subject.
- 7. The composition of claim 1 which disintegrates within about 15 seconds after placement in the oral cavity of a human subject.
- 8. The composition of claim 1 which upon oral administration to a human subject results in a valdecoxib concentration attaining a threshold for therapeutic effect within about 0.5 h of administration.
- 9. The composition of claim 1 which upon oral administration to a human subject results in a valdecoxib concentration attaining a threshold for therapeutic effect within about 0.3 h of administration.
- 10. The composition of claim 1 which upon oral administration to a human subject results in a time to reach maximum blood serum concentration (Tmax) not greater than about 5 h.
- 11. The composition of claim 1 which upon oral administration to a human subject results in a time to reach maximum blood serum concentration (Tmax) not greater than about 4.5 h.
- 12. The composition of claim 1 which upon oral administration to a human subject results in a maximum blood serum concentration (Cmax) not less than about 100 ng/ml.
- 13. The composition of claim 1 which upon oral administration to a human subject results in a maximum blood serum concentration (Cmax) not less than about 200 ng/ml.
- 14. The composition of claim 1 which upon oral administration to a human subject results in a maximum blood serum concentration (Cmax) not less than about 300 ng/ml.
- 15. The composition of claim 1 wherein the at least one pharmaceutically acceptable dissolution retardant is a polymer.
- 16. The composition of claim 15 wherein the polymer is present in a total amount of about 0.5% to about 15%, by weight.
- 17. The composition of claim 15 wherein the polymer is present in a total amount of about 0.75% to about 10%, by weight.
- 18. The composition of claim 15 wherein the polymer is present in a total amount of about 1.0% to about 5%, by weight.
- 19. The composition of claim 1 wherein the at least one pharmaceutically acceptable dissolution retardant is selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, Eudragit® EP O and equivalent polymethacrylate products, hydroxypropylethylcellulose and hydroxypropylcellulose.
- 20. The composition of claim 1 wherein the at least one pharmaceutically acceptable dissolution retardant is Eudragit® EP O or an equivalent polymethacrylate product.
- 21. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is a carbohydrate.
- 22. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is a saccharide.
- 23. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is selected from the group consisting of maltose, maltitol, sorbitol, lactose and mannitol.
- 24. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution comprises a saccharide of high moldability and a saccharide of low moldability.
- 25. The composition of claim 24 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 2 to about 20 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 26. The composition of claim 24 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 5 to about 10 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 27. The composition of claim 24 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 5 to about 7.5 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 28. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is present in a total amount of about 10% to about 90%, by weight.
- 29. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is present in a total amount of about 10% to about 80%, by weight.
- 30. The composition of claim 1 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is present in a total amount of about 10% to about 75%, by weight.
- 31. The composition of claim 1 having a hardness of about 1 to about 10 kp.
- 32. The composition of claim 1 having a hardness of about 1 to about 6 kp.
- 33. The composition of claim 1 wherein the valdecoxib is present in an amount of about 5 to about 50 mg.
- 34. The composition of claim 1 wherein the valdecoxib has a D90 particle size not greater than about 75 μm.
- 35. The composition of claim 1 wherein the valdecoxib has a D90 particle of about 1 to about 10 μm.
- 36. A process for preparing an intraorally disintegrating valdecoxib fast-melt composition, the process comprising:
a step of providing valdecoxib in particulate form; a step of adding to the valdecoxib at least one pharmaceutically acceptable dissolution retardant to form a valdecoxib composite; a step of admixing with the valdecoxib composite at least one pharmaceutically acceptable excipient that exhibits rapid oral dissolution, said admixing step forming a tableting blend; a step of granulating the valdecoxib, valdecoxib composite, or tableting blend; and a step of compressing the tableting blend to form the fast-melt composition; wherein said granulating step occurs prior to, simultaneously with, and/or after said step of adding the dissolution retardant.
- 37. The process of claim 36 wherein the granulating step comprises wet granulation.
- 38. The process of claim 37 further comprising a step of drying the valdecoxib composite or tableting blend during and/or after the wet granulation step.
- 39. The process of claim 38 wherein the drying step comprises tray drying in an oven.
- 40. The process of claim 38 wherein the drying step comprises fluid bed drying.
- 41. The process of claim 37 wherein the wet granulation step comprises high shear wet granulation.
- 42. The process of claim 37 wherein the wet granulation step comprises fluid bed granulation.
- 43. The process of claim 36 wherein the granulation step comprises dry granulation.
- 44. The process of claim 43 wherein the dry granulation step comprises roller compaction.
- 45. The process of claim 44 wherein the dry granulation step comprises slugging.
- 46. The process of claim 36 wherein the at least one pharmaceutically acceptable dissolution retardant is a polymer.
- 47. The process of claim 36 wherein the at least one pharmaceutically acceptable dissolution retardant is selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, Eudragit® EP O and equivalent polymethacrylate products, hydroxypropylethylcellulose and hydroxypropylcellulose.
- 48. The process of claim 36 wherein the at least one dissolution retardant is Eudragit® EP O or an equivalent polymethacrylate product.
- 49. The process of claim 36 wherein the dissolution retardant is added in a total amount of about 0.5% to about 15%, by weight of the composition.
- 50. The process of claim 36 wherein the dissolution retardant is added in a total amount of about 0.75% to about 10%, by weight of the composition.
- 51. The process of claim 36 wherein the dissolution retardant is added in a total amount of about 1.0% to about 5%, by weight of the composition.
- 52. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is a carbohydrate.
- 53. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is a saccharide.
- 54. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is selected from the group consisting of maltose, maltitol, sorbitol, lactose and mannitol.
- 55. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution comprises a saccharide of high moldability and a saccharide of low moldability.
- 56. The process of claim 55 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 2 to about 20 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 57. The process of claim 36 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 5 to about 10 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 58. The process of claim 36 wherein the weight ratio of saccharide of high moldability to saccharide of low moldability is about 5 to about 7.5 parts of saccharide of high moldability per 100 parts of saccharide of low moldability.
- 59. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is admixed in a total amount of about 10% to about 90%, by weight of the composition.
- 60. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is admixed in a total amount of about 10% to about 80%, by weight of the composition.
- 61. The process of claim 36 wherein the at least one pharmaceutically acceptable excipient which exhibits rapid oral dissolution is admixed in a total amount of about 10% to about 75%, by weight of the composition.
- 62. A valdecoxib fast-melt composition prepared according to the process of claim 36.
- 63. A method for treating or preventing a medical condition or disorder in a subject where treatment with a cyclooxygenase-2 inhibitory drug is indicated, comprising oral administration to the subject a fast-melt of claim 1.
- 64. A method for treating or preventing a medical condition or disorder in a subject where treatment with a cyclooxygenase-2 inhibitory drug is indicated, comprising oral administration to the subject a composition of claim 62.
Parent Case Info
[0001] This application claims priority of U.S. provisional application serial No. 60/325,356 filed on Sep. 26, 2001.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60325356 |
Sep 2001 |
US |