Claims for Patent: 8,372,431

Summary for Patent: 8,372,431

Title:	Pharmaceutical composition comprising licarbazepine acetate
Abstract:	A pharmaceutical composition comprising licarbazepine acetate, especially eslicarbazepine acetate, in combination with suitable excipients, in particular a binder, and a disintegrant. Also disclosed is a granulation process, especially a wet granulation process, for making the pharmaceutical composition.
Inventor(s):	Cardoso de Vasconcelos; Teofilo (S. Mamede do Coronado, PT), dos Santos Lima; Ricardo Jorge (S. Mamede do Coronado, PT), Cerdeira de Campos Costa; Rui (S. Mamede do Coronado, PT)
Assignee:	BIAL-Portela & C.A., S.A. (S. Mamede do Coronado, PT)
Application Number:	12/257,240
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,372,431
Patent Claims:	1. A pharmaceutical composition consisting of the following: 80-90 wt % eslicarbazepine acetate, 3-10 wt % povidone, 3-10 wt % croscarmellose sodium, and 0.1-3 wt % magnesium stearate, wherein the composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 2. The pharmaceutical composition of claim 1, wherein the eslicarbazepine acetate is intragranular. 3. The pharmaceutical composition of claim 1, wherein about half of the croscarmellose sodium is intragranular and the remaining about half is extragranular. 4. The pharmaceutical composition of claim 1, wherein the magnesium stearate is extragranular. 5. A pharmaceutical composition consisting of the following: 80-90 wt % eslicarbazepine acetate, 3-10 wt % povidone, 3-10 wt % croscarmellose sodium, and 0.1-3 wt % magnesium stearate, and at least one flavoring agent, wherein the composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 6. A pharmaceutical composition consisting of the following: 80-90 wt % eslicarbazepine acetate, 3-10 wt % povidone, 3-10 wt % croscarmellose sodium, and 0.1-3 wt % magnesium stearate, and at least one sweetening agent, wherein the composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 7. A pharmaceutical composition consisting of the following: 80-90 wt % eslicarbazepine acetate, 3-10 wt % povidone, 3-10 wt % croscarmellose sodium, and 0.1-3 wt % magnesium stearate, at least one flavoring agent, and at least one sweetening agent, wherein the composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 8. A solid pharmaceutical composition comprising: an intragranular phase comprising licarbazepine acetate, povidone, and croscarmellose sodium; and an extragranular phase comprising croscarmellose sodium and a lubricant; wherein the licarbazepine acetate is present in an amount ranging from 80 to 90 weight percent relative to the total weight of the solid pharmaceutical composition; wherein the povidone is present in an amount ranging from 3 to 10 weight percent relative to the total weight of the solid pharmaceutical composition; wherein the croscarmellose sodium is present in an amount ranging from 3 to 10 weight percent relative to the total weight of the solid pharmaceutical composition and is about equally apportioned between the intragranular phase and the extragranular phase; wherein the lubricant is present in an amount ranging from 0.1 to 3 weight percent relative to the total weight of the solid pharmaceutical composition; and wherein the solid pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 9. The solid pharmaceutical composition of claim 8, wherein the lubricant is magnesium stearate. 10. The solid pharmaceutical composition of claim 8, wherein the lubricant is sodium lauryl sulphate. 11. The solid pharmaceutical composition of claim 8, wherein the lubricant is a combination of magnesium stearate and sodium lauryl sulphate. 12. The solid pharmaceutical composition of claim 8, wherein the licarbazepine acetate is eslicarbazepine acetate. 13. The solid pharmaceutical composition of claim 9, wherein the licarbazepine acetate is eslicarbazepine acetate. 14. The solid pharmaceutical composition of claim 10, wherein the licarbazepine acetate is eslicarbazepine acetate. 15. The solid pharmaceutical composition of claim 11, wherein the licarbazepine acetate is eslicarbazepine acetate. 16. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits a dissolution of at least 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 17. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits a dissolution of at least 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 18. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition exhibits a dissolution of at least 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 19. The solid pharmaceutical composition of claim 14, wherein the solid pharmaceutical composition exhibits a dissolution of at least 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 20. The solid pharmaceutical composition of claim 15, wherein the solid pharmaceutical composition exhibits a dissolution of at least 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 21. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 22. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 23. The solid pharmaceutical composition of claim 14, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm. 24. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits an average dissolution of at least 70% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 6 oral dosage forms. 25. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits an average dissolution of at least 70% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 6 oral dosage forms. 26. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition exhibits an average dissolution of at least 70% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 6 oral dosage forms. 27. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition exhibits an average dissolution of at least 70% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 6 oral dosage forms. 28. The solid pharmaceutical composition of claim 13, wherein the solid pharmaceutical composition exhibits an average dissolution of at least 70% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 6 oral dosage forms. 29. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits a dissolution of at least 50% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 12 oral dosage forms. 30. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits a dissolution of at least 50% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 12 oral dosage forms. 31. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition exhibits a dissolution of at least 50% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 12 oral dosage forms. 32. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition exhibits a dissolution of at least 50% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 12 oral dosage forms. 33. The solid pharmaceutical composition of claim 13, wherein the solid pharmaceutical composition exhibits a dissolution of at least 50% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 12 oral dosage forms. 34. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits a dissolution of at least 40% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 24 oral dosage forms. 35. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits a dissolution of at least 40% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 24 oral dosage forms. 36. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition exhibits a dissolution of at least 40% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 24 oral dosage forms. 37. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition exhibits a dissolution of at least 40% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 24 oral dosage forms. 38. The solid pharmaceutical composition of claim 13, wherein the solid pharmaceutical composition exhibits a dissolution of at least 40% and an average dissolution of at least about 65% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm, wherein the average dissolution is calculated as an average of 24 oral dosage forms. 39. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm as described in Ph. Eur. edn 6, 2.9.3 or USP 21, <711>. 40. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm as described in Ph. Eur. edn 6, 2.9.3 or USP 21, <711>. 41. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm as described in Ph. Eur. edn 6, 2.9.3 or USP 21, <711>. 42. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm as described in Ph. Eur. edn 6, 2.9.3 or USP 21, <711>. 43. The solid pharmaceutical composition of claim 13, wherein the solid pharmaceutical composition exhibits a dissolution of at least 67.9% at about 30 minutes at a temperature of 37.+-.0.5.degree. C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm as described in Ph. Eur. edn 6, 2.9.3 or USP 21, <711>. 44. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 45. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 46. The pharmaceutical composition of claim 21, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 47. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 48. The pharmaceutical composition of claim 29, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 49. The pharmaceutical composition of claim 34, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 50. The pharmaceutical composition of claim 39, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 51. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 52. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 53. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 54. The solid pharmaceutical composition of claim 13, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 55. The solid pharmaceutical composition of claim 18, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 56. The solid pharmaceutical composition of claim 19, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 57. The solid pharmaceutical composition of claim 20, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 58. The solid pharmaceutical composition of claim 23, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 59. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 60. The solid pharmaceutical composition of claim 26, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 61. The solid pharmaceutical composition of claim 27, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 62. The solid pharmaceutical composition of claim 28, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 63. The solid pharmaceutical composition of claim 30, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 64. The solid pharmaceutical composition of claim 31, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 65. The solid pharmaceutical composition of claim 36, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 66. The solid pharmaceutical composition of claim 37, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 67. The solid pharmaceutical composition of claim 38, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 68. The solid pharmaceutical composition of claim 41, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 69. The solid pharmaceutical composition of claim 42, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 70. The solid pharmaceutical composition of claim 43, wherein the solid pharmaceutical composition has an apparent density of about 0.5 to about 1.5 g/mL. 71. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has an apparent density of about 0.6 to about 1.4 g/mL. 72. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition has an apparent density of about 0.6 to about 1.4 g/mL. 73. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition has an apparent density of about 0.6 to about 1.4 g/mL. 74. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition has an apparent density of about 0.6 to about 1.4 g/mL. 75. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has an apparent density of about 0.7 to about 1.3 g/mL. 76. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition has an apparent density of about 0.7 to about 1.3 g/mL. 77. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition has an apparent density of about 0.7 to about 1.3 g/mL. 78. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has an apparent density of about 0.8 to about 1.1 g/mL. 79. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition has an apparent density of about 0.8 to about 1.1 g/mL. 80. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition has an apparent density of about 0.8 to about 1.1 g/mL. 81. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition comprises no filler or diluent. 82. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition comprises no filler or diluent. 83. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a tablet or capsule. 84. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition is a tablet or capsule. 85. The solid pharmaceutical composition of claim 9, wherein the solid pharmaceutical composition is a tablet or capsule. 86. The solid pharmaceutical composition of claim 12, wherein the solid pharmaceutical composition is a tablet or capsule.