Claims for Patent: 7,014,867

Summary for Patent: 7,014,867

Title:	Tablet comprising cetirizine and pseudoephedrine
Abstract:	The present invention concerns a tablet comprising two distinct segments. More particularly, the invention relates to combinations of two pharmaceutical substances and methods of treatment of allergic disorders.
Inventor(s):	Fanara; Domenico (Wanze, BE), Guichaux; Anthony (Fribourg, CH), Berwaer; Monique (Ham-sur-Heure-Nalinnes, BE), Deleers; Michel (Linkebeek, BE)
Assignee:	UCB Farchim SA (Bulle, CH)
Application Number:	10/481,264
Patent Claims:	1. A tablet comprising at least two distinct segments, one segment of which comprises as active ingredient predominantly cetirizine and a second segment of which comprises as active ingredient predominantly pseudoephedrine, said segments being composed and formed in such a way that the resulting tablet is substantially free of impurities formed by reaction of cetirizine with pseudoephedrine, wherein the interfacial surface area of the pseudoephedrine segment and cetirizine segment is less than 180 mm.sup.2 and with the proviso that the tablet comprises less than 5% by weight, relative to the total weight of the tablet, of an alkalinizing agent. 2. A tablet according to claim 1 wherein the pseudoephedrine segment is substantially free of cetirizine. 3. A tablet according to claim 1 wherein the cetirizine segment is substantially free of pseudoephedrine. 4. A tablet according to claim 1 wherein the tablet further comprises a barrier segment wherein said barrier segment separates the cetirizine segment and the pseudoephedrine segment. 5. A tablet according to claim 1 wherein the pseudoephedrine segment comprises less than 5% by weight, relative to the total weight of the pseudoephedrine segment, of an alkalinizing agent. 6. A tablet according to claim 1 wherein the tablet comprises a plurality of pseudoephedrine segments. 7. A tablet according to claim 1 wherein said cetirizine segment is in the form of a compression coating. 8. A tablet according to claim 1 wherein said cetirizine segment is in the form of a spray coating. 9. A tablet according to claim 1 wherein the pseudoephedrine segment contains inert pharmaceutical excipients in an amount of 0.75 to 4.5 times that of the pseudoephedrine itself by weight. 10. A tablet according to claim 1 wherein the cetirizine segment contains inert pharmaceutical excipients in an amount of 5 to 30 times that of the cetirizine itself by weight. 11. A tablet according to claim 1 wherein the ratio of the total amount of inert pharmaceutical excipients present to the total aggregate amount of all active ingredients is between 2 and 6 by weight. 12. A tablet according to claim 1 wherein the weight ratio of pseudoephedrine to cetirizine is between 12 and 30. 13. A tablet according to claim 12 wherein the weight ratio of pseudoephedrine to cetirizine is about 24. 14. A tablet according to claim 1 wherein the pseudoephedrine segment comprises between about 108 and 132 mg of pseudoephedrine and the cetirizine segment comprises between about 4.5 and 5.5 mg of cetirizine. 15. A tablet according to claim 1 wherein the pseudoephedrine segment is in a slow release form. 16. A tablet according to claim 1 wherein the cetirizine is in an immediate release form. 17. A tablet according to claim 1 wherein the tablet weight is between 200 to 800 mg. 18. A tablet according to claim 1 wherein the tablet comprises an amount of cetirizine which when dosed to a human subject gives a cetirizine area under the plasma cetirizine concentration versus time curve which is between 80% and 125% of the area under the plasma cetirizine concentration versus time curve observed when a dihydrochloride cetirizine immediate release tablet comprising said amount of cetirizine is dosed to same human subject at the same cetirizine dose. 19. A tablet according to claim 1 wherein the tablet comprises an amount of pseudoephedrine which when dosed to a human subject gives a pseudoephedrine area under the pseudoephedrine plasma concentration versus time curve which is between 80% and 125% of the area under the plasma pseudoephedrine concentration versus time curve observed when a pseudoephedrine sustained release tablet comprising said amount of pseudoephedrine is dosed to same human subject. 20. A tablet according to claim 1 wherein the particle size of the pseudoephedrine present is chosen such that it has a flow index less than 25. 21. A tablet according to claim 1 wherein the particle size of the pseudoephedrine present is chosen such that it has an ability to settle of less than 30 ml. 22. A tablet according to claim 1 wherein not more than 10% of the pseudoephedrine present therein has a particle size of less than 100 .mu.m. 23. A tablet according to claim 21 wherein the particle size of the pseudoephedrine is such that at least 95% of the particles are less than 500 .mu.m and not more than 15% are less than 106 .mu.m. 24. A tablet according to claim 21 wherein the pseudoephedrine is crystalline. 25. A tablet according to claim 1 wherein the pseudoephedrine containing segment also contains a methyl cellulose ether derivative having a viscosity of about 11,000 to 21,000 mPa. 26. A tablet according to claim 25 wherein the methyl cellulose ether derivative is a substituted hydroxylated methyl cellulose. 27. A tablet according to claim 25 wherein the methyl cellulose ether derivative is an hydroxypropylmethylcellulose. 28. A tablet according to claim 27 wherein the derivative is an hydroxypropylmethylcellulose (methoxyl: 19 24%, hydroxypropyl: 7 12%), chlorides: max 0.5%; having an apparent viscosity of 11250 to 21000 mPa and a particle size: min 90%<100 mesh. 29. A tablet according to claim 25 wherein the ratio of hydroxypropylmethylcellulose (HPMC) to the pseudoephedrine is between 0.5 to 2 by weight. 30. A tablet according to claim 1 wherein the cetirizine containing segment also contains a disintegrant. 31. A tablet according to claim 30 wherein the cetirizine containing segment also contains a disintegrant in the range less than 5% by weight of cetirizine segment. 32. A tablet according to claim 30 wherein the disintegrant is a cross-linked carboxy methyl cellulose. 33. A tablet according to claim 1 wherein the cetirizine segment contains excipients including a polyhydroxyl compound having a molecular weight of less than 400. 34. A tablet according to claim 33 wherein the polyhydroxyl compound is a sugar. 35. A tablet according to claim 34 wherein the sugar is lactose. 36. A tablet according to claim 1 wherein the tablet is a bi-layer tablet, the cetirizine segment being a layer and the pseudoephedrine segment being a layer. 37. A tablet according to claim 36 wherein the weight ratio of the pseudoephedrine layer to the cetirizine layer is between 0.25 to 10. 38. A tablet according to claim 36 wherein the outer face of each of the two layers has a different shape. 39. A tablet according to claim 38 wherein the tablet has a first face which is the pseudoephedrine layer, having multiple radii of curvature. 40. A tablet according to claim 38 wherein the tablet has a second face which is the cetirizine layer, having a single radius of curvature. 41. A tablet according to claim 1 which comprises an additional coating layer. 42. A tablet according to claim 41 wherein the coating layer can act as a taste masking agent. 43. A tablet according to claim 1 wherein the tablet is packaged in a moisture protective packaging material. 44. A tablet according to claim 1 wherein the tablet is packaged in an oxygen protective packaging material. 45. A tablet according to claim 1 wherein the cetirizine segment comprises cetirizine dihydrochloride. 46. A tablet according to claim 1 wherein the cetirizine segment comprises levocetirizine. 47. A tablet comprising at least two distinct segments, one segment of which comprises as active ingredient predominantly cetirizine and a second segment of which comprises as active ingredient predominantly pseudoephedrine, wherein the interfacial surface area of the pseudoephedrine segment and cetirizine segment is less than 180 mm.sup.2, said segments being composed and formed in such a way that the pharmacokinetic profiles of the cetirizine and pseudoephedrine are substantially the same as in a dosage form containing each as sole active ingredient in the same amount. 48. A tablet according to claim 47 wherein the pseudoephedrine segment is substantially free of cetirizine. 49. A tablet according to claim 47 wherein the cetirizine segment is substantially free of pseudoephedrine. 50. A tablet according to claim 47 wherein the tablet further comprises a barrier segment wherein said barrier segment separates the cetirizine segment and the pseudoephedrine segment. 51. A tablet according to claim 47 wherein the pseudoephedrine segment comprises less than 5% by weight, relative to the total weight of the pseudoephedrine segment, of an alkalinizing agent. 52. A tablet according to claim 47 wherein the tablet comprises a plurality of pseudoephedrine segments. 53. A tablet according to claim 47 wherein said cetirizine segment is in the form of a compression coating. 54. A tablet according to claim 47 wherein said cetirizine segment is in the form of a spray coating. 55. A tablet according to claim 47 wherein the pseudoephedrine segment contains inert pharmaceutical excipients in an amount of 0.75 to 4.5 times that of the pseudoephedrine itself by weight. 56. A tablet according to claim 47 wherein the cetirizine segment contains inert pharmaceutical excipients in an amount of 5 to 30 times that of the cetirizine itself by weight. 57. A tablet according to claim 47 wherein the ratio of the total amount of inert pharmaceutical excipients present to the total aggregate amount of all active ingredients is between 2 and 6 by weight. 58. A tablet according to claim 47 wherein the weight ratio of pseudoephedrine to cetirizine is between 12 and 30. 59. A tablet according to claim 58 wherein the weight ratio of pseudoephedrine to cetirizine is about 24. 60. A tablet according to claim 47 wherein the pseudoephedrine segment comprises between about 108 and 132 mg of pseudoephedrine and the cetirizine segment comprises between about 4.5 and 5.5 mg of cetirizine. 61. A tablet according to claim 47 wherein the pseudoephedrine segment is in a slow release form. 62. A tablet according to claim 47 wherein the cetirizine is in an immediate release form. 63. A tablet according to claim 47 wherein the tablet weight is between 200 to 800 mg. 64. A tablet according to claim 47 wherein the tablet comprises an amount of cetirizine which when dosed to a human subject gives a cetirizine area under the plasma cetirizine concentration versus time curve which is between 80% and 125% of the area under the plasma cetirizine concentration versus time curve observed when a dihydrochloride cetirizine immediate release tablet comprising said amount of cetirizine is dosed to same human subject at the same cetirizine dose. 65. A tablet according to claim 47 wherein the tablet comprises an amount of pseudoephedrine which when dosed to a human subject gives a pseudoephedrine area under the pseudoephedrine plasma concentration versus time curve which is between 80% and 125% of the area under the plasma pseudoephedrine concentration versus time curve observed when a pseudoephedrine sustained release tablet comprising said amount of pseudoephedrine is dosed to same human subject. 66. A tablet according to claim 47 wherein the particle size of the pseudoephedrine present is chosen such that it has a flow index less than 25. 67. A tablet according to claim 47 wherein the particle size of the pseudoephedrine present is chosen such that it has an ability to settle of less than 30 ml. 68. A tablet according to claim 47 wherein not more than 10% of the pseudoephedrine present therein has a particle size of less than 100 .mu.m. 69. A tablet according to claim 67 wherein the particle size of the pseudoephedrine is such that at least 95% of the particles are less than 500 .mu.m and not more than 15% are less than 106 .mu.m. 70. A tablet according to claim 67 wherein the pseudoephedrine is crystalline. 71. A tablet according to claim 47 wherein the pseudoephedrine containing segment also contains a methyl cellulose ether derivative having a viscosity of about 11,000 to 21,000 mPa. 72. A tablet according to claim 71 wherein the methyl cellulose ether derivative is a substituted hydroxylated methyl cellulose. 73. A tablet according to claim 71 wherein the methyl cellulose ether derivative is an hydroxypropylmethylcellulose. 74. A tablet according to claim 73 wherein the derivative is an hydroxypropylmethylcellulose (methoxyl: 19 24%, hydroxypropyl: 7 12%), chlorides: max 0.5%; having an apparent viscosity of 11250 to 21000 mPa and a particle size: min 90%<100 mesh. 75. A tablet according to claim 71 wherein the ratio of hydroxypropylmethylcellulose (HPMC) to the pseudoephedrine is between 0.5 to 2 by weight. 76. A tablet according to claim 47 wherein the cetirizine containing segment also contains a disintegrant. 77. A tablet according to claim 76 wherein the cetirizine containing segment also contains a disintegrant in the range less than 5% by weight of cetirizine segment. 78. A tablet according to claim 76 wherein the disintegrant is a cross-linked carboxy methyl cellulose. 79. A tablet according to claim 47 wherein the cetirizine segment contains excipients including a polyhydroxyl compound having a molecular weight of less than 400. 80. A tablet according to claim 79 wherein the polyhydroxyl compound is a sugar. 81. A tablet according to claim 80 wherein the sugar is lactose. 82. A tablet according to claim 47 wherein the tablet is a bi-layer tablet, the cetirizine segment being a layer and the pseudoephedrine segment being a layer. 83. A tablet according to claim 82 wherein the weight ratio of the pseudoephedrine layer to the cetirizine layer is between 0.25 to 10. 84. A tablet according to claim 82 wherein the outer face of each of the two layers has a different shape. 85. A tablet according to claim 84 wherein the tablet has a first face which is the pseudoephedrine layer, having multiple radii of curvature. 86. A tablet according to claim 84 wherein the tablet has a second face which is the cetirizine layer, having a single radius of curvature. 87. A tablet according to claim 47 which comprises an additional coating layer. 88. A tablet according to claim 87 wherein the coating layer can act as a taste masking agent. 89. A tablet according to claim 47 wherein the tablet is packaged in a moisture protective packaging material. 90. A tablet according to claim 47 wherein the tablet is packaged in an oxygen protective packaging material. 91. A tablet according to claim 47 wherein the cetirizine segment comprises cetirizine dihydrochloride. 92. A tablet according to claim 47 wherein the cetirizine segment comprises levocetirizine.