Claims for Patent: 8,791,160

Summary for Patent: 8,791,160

Title:	Tranexamic acid formulations
Abstract:	Disclosed are modified release oral tranexamic acid formulations and methods of treatment therewith.
Inventor(s):	Moore; Keith A. (Loveland, OH), Heasley; Ralph A. (Webster Grove, MO), Greiwe; Jeffrey S. (Ft. Thomas, KY), Facemire; John W. (Douglasville, GA), Modest; Jason D. (Minneapolis, MN)
Assignee:	Ferring B.V. (Hoofddorp, NL)
Application Number:	13/620,226
Patent Claims:	1. A tranexamic acid tablet formulation comprising: tranexamic acid or a pharmaceutically acceptable salt thereof; and a modified release material; wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 50% to about 95% by weight of the formulation; wherein the modified release material is present in an amount from about 5% to about 50% by weight of the formulation; and wherein said tablet formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by a USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37.+-.0.5.degree. C., of less than about 70% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, and about 100% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 120 minutes. 2. The tranexamic acid tablet formulation of claim 1, wherein said tablet formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by a USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37.+-.0.5.degree. C., of less than about 40% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, less than about 70% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, and not less than about 50% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 90 minutes. 3. The tranexamic acid tablet formulation of claim 1, wherein said formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by the USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37.+-.0.5.degree. C., of about 0% to about 40% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, from about 20% to about 60% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 30 minutes, from about 40% to about 65% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, from about 50% to about 95% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 60 minutes, and not less than about 60% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 90 minutes. 4. The tranexamic acid tablet formulation of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 5. The tranexamic acid tablet formulation of claim 1, wherein formulation provides a dose of about 650 mg of tranexamic acid per tablet. 6. The tranexamic acid tablet formulation of claim 5, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 7. The tranexamic acid tablet formulation of claim 1, wherein the modified release material comprises hydroxypropylmethylcellulose. 8. The tranexamic acid tablet formulation of claim 7, wherein formulation provides a dose of about 650 mg of tranexamic acid per tablet. 9. The tranexamic acid tablet formulation of claim 8, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 10. The tranexamic acid tablet formulation of claim 1, wherein the formulation is in the form of a matrix tablet which comprises a drug mixed together with a granulated modified release material. 11. The tranexamic acid tablet formulation of claim 10, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 12. The tranexamic acid tablet formulation of claim 11, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 13. The tranexamic acid tablet formulation of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation. 14. The tranexamic acid tablet formulation of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 80% by weight of the formulation. 15. The tranexamic acid tablet formulation of claim 1, wherein the modified release material is present in an amount from about 10% to about 35% by weight of the formulation. 16. The tranexamic acid tablet formulation of claim 1, wherein: the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation; the formulation is in the form of a matrix tablet which comprises a granulated drug mixed together with the modified release material and the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 17. The tranexamic acid tablet formulation of claim 16, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 18. The tranexamic acid tablet formulation of claim 16, wherein the modified release material comprises hydroxypropylmethylcellulose. 19. The tranexamic acid tablet formulation of claim 18, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 20. A tranexamic acid tablet formulation comprising: tranexamic acid or a pharmaceutically acceptable salt thereof; and a modified release material; wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 50% to about 95% by weight of the formulation; wherein the modified release material is present in an amount from about 5% to about 50% by weight of the formulation; and wherein said tablet formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by a USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37.+-.0.5.degree. C., of less than about 40% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, and about 100% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 120 minutes. 21. The tranexamic acid tablet formulation of claim 20, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 22. The tranexamic acid tablet formulation of claim 20, wherein formulation provides a dose of about 650 mg of tranexamic acid per tablet. 23. The tranexamic acid tablet formulation of claim 22, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 24. The tranexamic acid tablet formulation of claim 20, wherein the modified release material comprises hydroxypropylmethylcellulose. 25. The tranexamic acid tablet formulation of claim 24, wherein formulation provides a dose of about 650 mg of tranexamic acid per tablet. 26. The tranexamic acid tablet formulation of claim 25, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 27. The tranexamic acid tablet formulation of claim 20, wherein the formulation is in the form of a matrix tablet which comprises a drug mixed together with a granulated modified release material. 28. The tranexamic acid tablet formulation of claim 27, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 29. The tranexamic acid tablet formulation of claim 28, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 30. The tranexamic acid tablet formulation of claim 20, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation. 31. The tranexamic acid tablet formulation of claim 20, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 80% by weight of the formulation. 32. The tranexamic acid tablet formulation of claim 20, wherein the modified release material is present in an amount from about 10% to about 35% by weight of the formulation. 33. The tranexamic acid tablet formulation of claim 20, wherein: the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation; the formulation is in the form of a matrix tablet which comprises a granulated drug mixed together with the modified release material and the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 34. The tranexamic acid tablet formulation of claim 33, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 35. The tranexamic acid tablet formulation of claim 33, wherein the modified release material comprises hydroxypropylmethylcellulose. 36. The tranexamic acid tablet formulation of claim 35, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 37. An oral dosage form comprising a tranexamic acid tablet formulation according to claim 1 coated with a film. 38. The oral dosage form of claim 37, wherein the film comprises a film-forming agent present in an amount in the range from about 2% tablet weight to about 4% tablet weight. 39. The oral dosage form of claim 37, wherein the film comprises a film-forming agent forming agent that comprises a (diethylaminoethyl)methacrylate/methyl-butyl-methacrylate copolymer. 40. The oral dosage form of claim 39, wherein the film forming agent comprises Eudragit E. 41. The oral dosage form of claim 37, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 42. The oral dosage form of claim 37, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 43. The oral dosage form of claim 42, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 44. The oral dosage form of claim 37, wherein the modified release material comprises hydroxypropylmethylcellulose. 45. The oral dosage form of claim 44, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 46. The oral dosage form of claim 45, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 47. The oral dosage form of claim 37, wherein the formulation is in the form of a matrix tablet which comprises a drug mixed together with a granulated modified release material. 48. The oral dosage form of claim 47, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 49. The oral dosage form of claim 48, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 50. The oral dosage form of claim 37, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation. 51. The oral dosage form of claim 37, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 80% by weight of the formulation. 52. The oral dosage form of claim 37, wherein the modified release material is present in an amount from about 10% to about 35% by weight of the formulation. 53. The oral dosage form of claim 37, wherein: the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation; the formulation is in the form of a matrix tablet which comprises a granulated drug mixed together with the modified release material and the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 54. The oral dosage form of claim 53, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 55. The oral dosage form of claim 53, wherein the modified release material comprises hydroxypropylmethylcellulose. 56. The oral dosage form of claim 55, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 57. An oral dosage form comprising a tranexamic acid tablet formulation according to claim 20 coated with a film. 58. The oral dosage form of claim 57, wherein the film comprises a film-forming agent present in an amount in the range from about 2% tablet weight to about 4% tablet weight. 59. The oral dosage form of claim 57, wherein the film comprises a film-forming agent forming agent that comprises a (diethylaminoethyl)methacrylate/methyl-butyl-methacrylate copolymer. 60. The oral dosage form of claim 59, wherein the film forming agent comprises Eudragit E. 61. The oral dosage form of claim 57, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 62. The oral dosage form of claim 57, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 63. The oral dosage form of claim 62, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 64. The oral dosage form of claim 57, wherein the modified release material comprises hydroxypropylmethylcellulose. 65. The oral dosage form of claim 64, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 66. The oral dosage form of claim 65, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 67. The oral dosage form of claim 57, wherein the formulation is in the form of a matrix tablet which comprises a drug mixed together with a granulated modified release material. 68. The oral dosage form of claim 67, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 69. The oral dosage form of claim 68, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 70. The oral dosage form of claim 57, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation. 71. The oral dosage form of claim 57, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 80% by weight of the formulation. 72. The oral dosage form of claim 57, wherein the modified release material is present in an amount from about 10% to about 35% by weight of the formulation. 73. The oral dosage form of claim 57, wherein: the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation; the formulation is in the form of a matrix tablet which comprises a granulated drug mixed together with the modified release material and the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 74. The oral dosage form of claim 73, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 75. The oral dosage form of claim 73, wherein the modified release material comprises hydroxypropylmethylcellulose. 76. The oral dosage form of claim 75, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid. 77. A method of treating menorrhagia comprising administering to a patient in need of such treatment at least one tablet of the tranexamic acid formulation of claim 1, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 78. A method of treating menorrhagia comprising administering to a patient in need of such treatment at least one tablet of the tranexamic acid formulation of claim 20, wherein the formulation provides a dose of about 650 mg of tranexamic acid per tablet. 79. A method of treating menorrhagia comprising administering to a patient in need of such treatment at least one oral dosage form according to claim 37, wherein the oral dosage form provides a dose of about 650 mg of tranexamic acid. 80. A method of treating menorrhagia comprising administering to a patient in need of such treatment at least one oral dosage form according to claim 57, wherein the oral dosage form provides a dose of about 650 mg of tranexamic acid.