Claims for Patent: 6,489,346

Summary for Patent: 6,489,346

Title:	Substituted benzimidazole dosage forms and method of using same
Abstract:	There is provided a solid pharmaceutical composition in a dosage form that is not enteric-coated, having active ingredients including a non-enteric coated proton pump inhibitor and at least one buffering agent. The proton pump inhibitor is omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, and leminoprazole, or an enantiomer, isomer, derivative, free base, or salt thereof, in an amount of approximately 5 mg to approximately 300 mg; and the buffering agent is in an amount of approximately 0.1 mEq to approximately 2.5 mEq per mg of proton pump inhibitor. The dosage form includes a suspension tablet, a chewable tablet, an effervescent powder, or an effervescent tablet. Also provided is a method for treating an acid-related gastrointestinal disorder in a subject in need thereof by administering to the subject a solid pharmaceutical composition.
Inventor(s):	Phillips; Jeffrey Owen (Ashland, MO)
Assignee:	The Curators of the University of Missouri (Columbia, MO)
Application Number:	09/481,207
Patent Claims:	1. A solid pharmaceutical composition in a dosage form that is not enteric-coated, comprising: active ingredients consisting essentially of: (a) a non-enteric coated proton pump inhibitor selected from the group consisting of omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, and leminoprazole, or an enantiomer, isomer, free base, or salt thereof, in an amount of approximately 5 mg to approximately 300 mg; and (b) at least one buffering agent selected from the group consisting of sodium bicarbonate, potassium bicarbonate, a calcium salt, and a magnesium salt, in an amount of approximately 0.1 mEq to approximately 2.5 mEq per mg of proton pump inhibitor; wherein the dosage form is selected from the group consisting of suspension tablet, chewable tablet, effervescent powder, and effervescent tablet. 2. The composition as recited in claim 1, wherein the proton pump inhibitor is omeprazole. 3. The composition as recited in claim 1, wherein the proton pump inhibitor is lansoprazole. 4. The composition as recited in claim 1, wherein the proton pump inhibitor is rabeprazole. 5. The composition as recited in claim 1, wherein the proton pump inhibitor is esomeprazole. 6. The composition as recited in claim 1, wherein the proton pump inhibitor is pantoprazole. 7. The composition as recited in claim 1, wherein the proton pump inhibitor is pariprazole. 8. The composition as recited in claim 1, wherein the proton pump inhibitor is leminoprazole. 9. The composition as recited in claim 1, further comprising at least one flavoring agent. 10. The composition as recited in claim 1, further comprising an anti-foaming agent. 11. The composition as recited in claim 1, wherein the dosage form is a suspension tablet. 12. The composition as recited in claim 1, wherein the dosage form is a chewable tablet. 13. The composition as recited in claim 12, further comprising aspartame. 14. The composition as recited in claim 1, wherein the dosage form is an effervescent powder. 15. The composition as recited in claim 1, wherein the dosage form is an effervescent tablet. 16. The composition as recited in claim 1, wherein the buffering agent is at least about 1680 mg sodium bicarbonate. 17. The composition as recited in claim 1, wherein the buffering agent is about 1000 mg to about 1680 mg sodium bicarbonate. 18. A method of producing a liquid pharmaceutical composition, comprising: combining the composition recited in claim 11 with an aqueous medium. 19. A method of producing a liquid pharmaceutical composition, comprising: combining the composition recited in claim 12 with an aqueous medium. 20. A method of producing a liquid pharmaceutical composition, comprising: combining the composition recited in claim 14 with an aqueous medium. 21. A method of producing a liquid pharmaceutical composition, comprising: combining the composition recited in claim 15 with an aqueous medium. 22. A method for treating an acid-caused gastrointestinal disorder in a subject in need thereof, comprising: administering to the subject the dosage form of claim 1 via a route selected from the group consisting of oral, nasogastric, and gastric tube. 23. The method as recited in claim 22, wherein the disorder is selected from the group consisting of duodenal ulcer disease, gastric ulcer disease, gastroesophageal reflux disease, erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, pathological gastrointestinal hypersecretory disease, Zollinger Ellison Syndrome, and acid dyspepsia. 24. A method for treating an acid-caused gastrointestinal disorder in a subject in need thereof, comprising: administering to the subject a solid pharmaceutical composition in a dosage form that is not enteric-coated; wherein the composition comprises active ingredients consisting essentially of: (a) a therapeutically effective amount of approximately 5 mg to approximately 300 mg of a non-enteric coated proton pump inhibitor selected from the group consisting of omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, and leminoprazole, or an enantiomer, isomer, derivative, free base, or salt thereof; and (b) a buffering agent in an amount of approximately 1.0 mEq to approximately 150 mEq selected from the group consisting of a bicarbonate salt of a group IA metal, a calcium salt, and a magnesium salt, wherein the buffering agent is in an amount sufficient to elevate gastric acid pH of the subject's stomach to prevent or inhibit gastric acid degradation of the non-enteric coated proton pump inhibitor and achieve sufficient bioavailability of the proton pump inhibitor in the subject to elicit a therapeutic effect. 25. The method of claim 24, wherein the calcium salt is selected from the group consisting of calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium bicarbonate, calcium gluconate, and other calcium salts. 26. The method of claim 24, wherein the sodium bicarbonate is in an amount from about 1000 mg to about 1680 mg. 27. The method of claim 24, wherein the sodium bicarbonate is in an amount of at least about 1680 mg. 28. The method of claim 24, wherein the calcium salt is calcium carbonate present in an amount from about 250 mg to about 1000 mg. 29. The method of claim 24, wherein the calcium salt is calcium carbonate present in an amount from about 500 mg to about 1000 mg. 30. The method of claim 24, wherein the calcium salt is calcium carbonate present in an amount of at least about 1000 mg. 31. The method of claim 24, wherein the buffering agent is in an amount of at least 10 mEq. 32. The method of claim 24, wherein the buffering agent is in an amount from about 10 mEq to about 70 mEq. 33. The method of claim 24, wherein the buffering agent is in an amount from about 20 mEq to about 40 mEq. 34. The method of claim 24, wherein the proton pump inhibitor is in an amount from about 10 mg to about 100 mg. 35. The method of claim 24, wherein the proton pump inhibitor is omeprazole. 36. The method of claim 35, wherein the omeprazole is present in an amount of about 10 mg. 37. The method of claim 35, wherein the omeprazole is present in an amount of about 20 mg. 38. The method of claim 35, wherein the omeprazole is present in an amount of about 40 mg. 39. The method of claim 35, wherein the omeprazole is present in an amount of about 60 mg. 40. The method of claim 35, wherein the omeprazole is present in an amount of about 80 mg. 41. The method of claim 35, wherein the omeprazole is present in an amount of about 100 mg. 42. The method of claim 24, wherein the proton pump inhibitor is lansoprazole. 43. The method of claim 42, wherein the lansoprazole is present in an amount of about 15 mg. 44. The method of claim 42, wherein the lansoprazole is present in an amount of about 30 mg. 45. The method of claim 42, wherein the lansoprazole is present in an amount of about 45 mg. 46. The method of claim 42, wherein the lansoprazole is present in an amount of about 60 mg. 47. The method of claim 42, wherein the lansoprazole is present in an amount of about 90 mg. 48. The method of claim 42, wherein the lansoprazole is present in an amount of about 100 mg. 49. The method of claim 24, wherein the proton pump inhibitor is micronized. 50. The method of claim 24, wherein the composition is in a dosage form selected from the group consisting of a tablet, powder, suspension tablet, chewable tablet, capsule, effervescent powder, effervescent tablet, pellets, and granules. 51. The method of claim 24, wherein the subject is a human. 52. The method of claim 24, wherein the dosage form further comprises a flavoring agent. 53. The method of claim 52, wherein the flavoring agent comprises aspartame, chocolate, root beer, peppermint, spearmint, or watermelon, and combinations of any of the foregoing. 54. The method of claim 24, wherein the composition is provided as a separate component of a kit. 55. The method of claim 24, wherein the disorder is selected from the group consisting of duodenal ulcer disease, gastric ulcer disease, gastroesophageal reflux disease, erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, pathological gastrointestinal hypersecretory disease, Zollinger Ellison Syndrome, and acid dyspepsia. 56. The method of claim 24, wherein the dosage form is administered once or twice a day. 57. A solid pharmaceutical composition in a dosage form that is not enteric-coated, comprising: active ingredients consisting essentially of: (a) a therapeutically effective amount of a non-enteric coated proton pump inhibitor selected from the group consisting of omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, and leminoprazole, or an enantiomer, isomer, derivative, free base, or salt thereof; and (b) a buffering agent selected from the group consisting of sodium bicarbonate, and calcium carbonate, in an amount more than about 40 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 58. The composition as recited in claim 57, wherein the buffering agent is sodium bicarbonate. 59. The composition as recited in claim 57, wherein the sodium bicarbonate is in an amount from about 400 mg to about 4000 mg. 60. The composition as recited in claim 57, wherein the sodium bicarbonate is in an amount of at least about 800 mg. 61. The composition as recited in claim 57, wherein the buffering agent is calcium carbonate. 62. The composition as recited in claim 57, wherein the calcium carbonate is in an amount from about 400 mg to about 4000 mg. 63. The composition as recited in claim 61, wherein the calcium carbonate is in an amount from about 500 mg to about 1000 mg. 64. The composition as recited in claim 61, wherein the calcium carbonate is in an amount of at least about 800 mg. 65. The composition as recited in claim 57, wherein the proton pump inhibitor is in an amount from about 10 mg to about 100 mg. 66. The composition as recited in claim 57, wherein the proton pump inhibitor is omeprazole. 67. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 10 mg. 68. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 20 mg. 69. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 40 mg. 70. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 60 mg. 71. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 80 mg. 72. The composition as recited in claim 66, wherein the omeprazole is present in an amount of about 100 mg. 73. The composition as recited in claim 57, wherein the proton pump inhibitor is lansoprazole. 74. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 15 mg. 75. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 30 mg. 76. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 45 mg. 77. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 60 mg. 78. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 90 mg. 79. The composition as recited in claim 73, wherein the lansoprazole is present in an amount of about 100 mg. 80. The composition as recited in claim 57, wherein the proton pump inhibitor is micronized. 81. The composition as recited in claim 57, wherein the composition is in a dosage form selected from the group consisting of a tablet, powder, suspension tablet, chewable tablet, capsule, effervescent powder, effervescent tablet, pellets, and granules. 82. The composition as recited in claim 57, further comprising a flavoring agent comprising aspartame, chocolate, root beer, peppermint, spearmint, or watermelon, and combinations of any of the foregoing. 83. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 50 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 84. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 60 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 85. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 70 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 86. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 80 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 87. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 90 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 88. The composition as recited in claim 57, wherein the amount of the buffering agent is more than about 100 times the amount of the proton pump inhibitor on a weight to weight basis in the composition. 89. The composition as recited in claim 57, wherein the composition is provided as a separate component of a kit. 90. A method of producing a liquid pharmaceutical composition comprising: combining the dosage form of claim 57 with an aqueous medium. 91. A method for treating an acid-caused gastrointestinal disorder in a subject in need thereof, comprising: administering to the subject the dosage form as recited in claim 57 via a route selected from the group consisting of oral, nasogastric, and gastric tube. 92. The method as recited in claim 91, wherein the disorder is selected from the group consisting of duodenal ulcer disease, gastric ulcer disease, gastroesophageal reflux disease, erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, pathological gastrointestinal hypersecretory disease, Zollinger Ellison Syndrome, and acid dyspepsia. 93. The method as recited in claim 91, wherein the composition is administered once or twice a day. 94. A method for administering a liquid pharmaceutical composition to a subject, comprising: combining the pharmaceutical composition as recited in claim 57 with an aqueous medium to form a suspension, and orally administering the suspension to the subject in a single dose without administering an additional buffering agent. 95. The composition as recited in claim 1, wherein the proton pump inhibitor is in an amount from about 10 mg to about 100 mg. 96. The composition as recited in claim 95, wherein the proton pump inhibitor is omeprazole. 97. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 10 mg. 98. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 20 mg. 99. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 40 mg. 100. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 60 mg. 101. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 80 mg. 102. The composition as recited in claim 95, wherein the omeprazole is present in an amount of about 100 mg. 103. The composition as recited in claim 95, wherein the proton pump inhibitor is lansoprazole. 104. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 15 mg. 105. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 30 mg. 106. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 45 mg. 107. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 60 mg. 108. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 90 mg. 109. The composition as recited in claim 103, wherein the lansoprazole is present in an amount of about 100 mg. 110. The composition as recited in claim 1, wherein the proton pump inhibitor is micronized. 111. The composition as recited in claim 9, wherein the flavoring agent comprises aspartame, chocolate, root beer, peppermint, spearmint, or watermelon, and combinations of any of the foregoing. 112. The composition as recited in claim 1, wherein the composition is provided as a separate component of a kit. 113. The composition of claim 1, wherein the buffering agent comprises a bicarbonate salt of a Group IA metal. 114.The composition of claim 1, wherein the buffering agent comprises at least one of magnesium hydroxide, magnesium lactate, magnesium gluconate, magnesium oxide, magnesium carbonate, or magnesium silicate. 115. The composition of claim 1, wherein the buffering agent comprises at least one of calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium carbonate, calcium bicarbonate, calcium gluconate, or other calcium salts. 116. The composition of claim 1, further comprising a disintegrant, flow aid, lubricant, adjuvant excipient, colorant, diluent, moistening agent, preservative, and pharmaceutically compatible carrier. 117. The method of claim 24, wherein the composition further comprises a disintegrant, flow aid, lubricant, adjuvant, excipient, colorant, diluent, moistening agent, preservative, and pharmaceutically compatible carrier. 118. The composition of claim 57, further comprising a disintegrant, flow aid, lubricant, adjuvant, excipient, colorant, diluent, moistening agent, preservative, and pharmaceutically compatible carrier.