Fexofenadine suspension formulation

1. An aqueous pharmaceutical suspension, having a pH 5.8 to 7.0 adjusted by a buffer system, comprising, by weight/volume (g/100 mL),

0.03% to 4.80% of fexofenadine zwitterionic dihydrate Form I of formula (I) having a particle size of less than 280 μm for at least 90% of the fexofenadine zwitterionic dihydrate Form I;

0.01% to 0.20% of a wetting agent;

a suspending agent selected from 0.10% to 0.50% of a hydrocolloid gum, or 0.1% to 1.0% of hydroxyethylcellulose;

a sweetener system comprising

5% to 40% of sucrose or invert sucrose; and

5% to 40% of xylitol, sorbitol or sorbitol solution, or maltitol solution;

provided that the ratio of the amount of (sucrose or invert sucrose) : (xylitol, sorbitol or sorbitol solution, or maltitol solution) is 1:1 to 2:1; and

a preservative system comprising

0.010% to 0.058% of propylparaben, sodium propylparaben or potassium propylparaben;

0.0005% to 0.0350% of butylparaben or sodium butylparaben; and

0.06% to 0.26% of edetate disodium, 0.01% to 0.27% of benzoic acid or sodium benzoate, 0.01% to 0.30% of sorbic acid or potassium sorbate or 0.10% to 1.50% of benzyl alcohol.

2. The aqueous pharmaceutical suspension according to claim 1 , wherein the particle size is less than 50 μm for at least 90% of the fexofenadine zwitterionic dihydrate Form I.

3. The aqueous pharmaceutical suspension according to claim 1 , wherein the particle size is less than 40 μm for at least 90% of the fexofenadine zwitterionic dihydrate Form I.

4. The aqueous pharmaceutical suspension according to claim 3 , wherein the fexofenadine zwitterionic dihydrate Form I is, by weight/volume (g/100 mL), 0.6% to 1.2%.

5. The aqueous pharmaceutical suspension according to claim 3 , wherein the fexofenadine zwitterionic dihydrate Form I is, by weight/volume (g/100 mL), 0.6%.

6. The aqueous pharmaceutical suspension according to claim 3 , wherein the wetting agent is, by weight/volume (g/100 mL), 0.01% to 0.05%.

7. The aqueous pharmaceutical suspension according to claim 3 , wherein the wetting agent is, by weight/volume (g/100 mL), 0.02% to 0.05%.

8. The aqueous pharmaceutical suspension according to claim 3 , wherein the hydrocolloid gum is, by weight/volume (g/100 mL), 0.23% to 0.45%.

9. The aqueous pharmaceutical suspension according to claim 3 , wherein the hydrocolloid gum is, by weight/volume (g/100 mL), 0.35% to 0.45%.

10. The aqueous pharmaceutical suspension according to claim 3 , wherein the hydrocolloid gum is xanthan gum.

11. The aqueous pharmaceutical suspension according to claim 3 , wherein the hydroxyethylcellulose is, by weight/volume (g/100 mL), 0.2% to 0.4%.

12. The aqueous pharmaceutical suspension according to claim 3 , wherein the hydroxyethylcellulose is, by weight/volume (g/100 mL), 0.2% to 0.3%.

13. The aqueous pharmaceutical suspension according to claim 3 , wherein the xylitol, sorbitol or sorbitol solution, or maltitol solution is, by weight/volume (g/100 mL), 5% to 20%.

14. The aqueous pharmaceutical suspension according to claim 3 , wherein the xylitol, sorbitol or sorbitol solution, or maltitol solution is, by weight/volume (g/100 mL), 10% to 20%.

15. The aqueous pharmaceutical suspension according to claim 3 , wherein the xylitol, sorbitol or sorbitol solution, or maltitol solution is, by weight/volume (g/100 mL), 10%.

16. The aqueous pharmaceutical suspension according to claim 3 , wherein the sucrose or invert sucrose is, by weight/volume (g/100 mL), 10% to 40%.

17. The aqueous pharmaceutical suspension according to claim 3 , wherein the sucrose or invert sucrose is, by weight/volume (g/100 mL), 10% to 20%.

18. The aqueous pharmaceutical suspension according to claim 3 , wherein the sucrose or invert sucrose is, by weight/volume (g/100 mL), 20%.

19. The aqueous pharmaceutical suspension according to claim 3 , wherein the sweetener system comprises xylitol and sucrose.

20. The aqueous pharmaceutical suspension according to claim 3 , wherein the sweetener system comprises xylitol and sucrose, and the ratio of the amount of sucrose : xylitol is 2:1.

21. The aqueous pharmaceutical suspension according to claim 3 , wherein the sweetener system comprises, by weight/volume (g/100 mL), 0% to 20% of xylitol, and 10% to 40% of sucrose.

22. The aqueous pharmaceutical suspension according to claim 3 , wherein the sweetener system comprises, by weight/volume (g/100 mL), 10% to 20% of xylitol, and 10% to 20% of sucrose.

23. The aqueous pharmaceutical suspension according to claim 3 , wherein the sweetener system comprises, by weight/volume (g/100 mL), 20% of sucrose and 10% of xylitol.

24. The aqueous pharmaceutical suspension according to claim 3 , the ratio of the amount of (sucrose or invert sucrose):(xylitol, sorbitol or sorbitol solution, or maltitol solution) is 2:1.

25. The aqueous pharmaceutical suspension according to claim 3 , wherein the propylparaben, sodium propylparaben, or potassium propylparaben is, by weight/volume (g/100 mL), 0.014% to 0.048%.

26. The aqueous pharmaceutical suspension according to claim 3 , wherein the propylparaben, sodium propylparaben, or potassium propylparaben is, by weight/volume (g/100 mL), 0.027% to 0.040%.

27. The aqueous pharmaceutical suspension according to claim 3 , wherein the butylparaben, or sodium butylparaben is, by weight/volume (g/100 mL), 0.0008% to 0.0240%.

28. The aqueous pharmaceutical suspension according to claim 3 , wherein the butylparaben, or sodium butylparaben is, by weight/volume (g/100 mL), 0.014% to 0.020%.

29. The aqueous pharmaceutical suspension according to claim 3 , wherein the edetate disodium is, by weight/volume (g/100 mL), 0.10% to 0.18%.

30. The aqueous pharmaceutical suspension according to claim 3 , wherein the edetate disodium is, by weight/volume (g/100 mL), 0.12% to 0.18%.

31. The aqueous pharmaceutical suspension according to claim 3 , wherein the preservative system comprises propylparaben, butylparaben and edetate disodium.

32. The aqueous pharmaceutical suspension according to claim 3 , wherein the benzoic acid or sodium benzoate is, by weight/volume (g/100 mL), 0.10% to 0.20%.

33. The aqueous pharmaceutical suspension according to claim 3 , wherein the benzoic acid or sodium benzoate is, by weight/volume (g/100 mL), 0.12% to 0.18%.

34. The aqueous pharmaceutical suspension according to claim 3 , wherein the sorbic acid or potassium sorbate is, by weight/volume (g/100 mL), 0.10% to 0.22%.

35. The aqueous pharmaceutical suspension according to claim 3 , wherein the sorbic acid or potassium sorbate is, by weight/volume (g/100 mL), 0.12% to 0.20%.

36. The aqueous pharmaceutical suspension according to claim 3 , wherein the benzyl alcohol is, by weight/volume (g/100 mL), 0.25% to 1.00%.

37. The aqueous pharmaceutical suspension according to claim 3 , wherein the benzyl alcohol is, by weight/volume (g/100 mL), 0.24% to 0.50%.

38. The aqueous pharmaceutical suspension according to claim 3 , wherein the buffering uses a buffer system comprising, by weight/volume (g/100 mL),

0.75% of sodium phosphate monobasic or a corresponding equivalent amount of a sodium phosphate monobasic hydrate, or 0.89% of potassium phosphate monobasic; and

1.25% of sodium phosphate dibasic or a corresponding equivalent amount of a sodium phosphate dibasic hydrate, or 1.86% of potassium phosphate dibasic or a corresponding equivalent amount of a potassium phosphate dibasic hydrate.

39. The aqueous pharmaceutical suspension according to claim 6 , wherein the buffering uses a buffer system comprising, by weight/volume (g/100 mL),

0.75% of sodium phosphate monobasic or a corresponding equivalent amount of a sodium phosphate monobasic hydrate; and

1.25% of sodium phosphate dibasic or a corresponding equivalent amount of a sodium phosphate dibasic hydrate.

40. The aqueous pharmaceutical suspension according to claim 3 , wherein the wetting agent is nonionic.

41. The aqueous pharmaceutical suspension according to claim 3 , wherein the wetting agent is Poloxamer 407 or Poloxamer 188.

42. The aqueous pharmaceutical suspension according to claim 3 , wherein the wetting agent is Poloxamer 407.

43. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.1% to 3.0% of microcrystalline cellulose.

44. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 1.0% to 2.0% of microcrystalline cellulose.

45. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 1.5% to 2.0% of microcrystalline cellulose.

46. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.01% to 0.20% of saccharin.

47. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.012% to 0.130% of saccharin.

48. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.05% to 0.10% of saccharin.

49. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.01% to 1.00% of acesulfame potassium or sucralose.

50. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.01% to 0.50% of acesulfame potassium or sucralose.

51. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.01% to 0.10% of acesulfame potassium or sucralose.

52. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.1% to 15.0% of propylene glycol.

53. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 1.0% to 10.0% of propylene glycol.

54. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 2.5% to 5.0% of propylene glycol.

55. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0% to 4% of polyethylene glycol 200, polyethylene glycol 300 or polyethylene glycol 400.

56. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0% to 2% of polyethylene glycol 200, polyethylene glycol 300 or polyethylene glycol 400.

57. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0% to 1% of polyethylene glycol 200, polyethylene glycol 300 or polyethylene glycol 400.

58. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0% to 0.50% of an opacifying agent.

59. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0% to 0.10% of an opacifying agent.

60. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.05% to 0.10% of an opacifying agent.

61. The aqueous pharmaceutical suspension according to claim 58 , wherein the opacifying agent is titanium dioxide.

62. The aqueous pharmaceutical suspension according to claim 59 , wherein the opacifying agent is titanium dioxide.

63. The aqueous pharmaceutical suspension according to claim 60 , wherein the opacifying agent is Titanium dioxide.

64. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.20% to 0.70% of a flavoring agent.

65. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.30% to 0.45% of a flavoring agent.

66. The aqueous pharmaceutical suspension according to claim 3 , further comprising, by weight/volume (g/100 mL), 0.40% to 0.45% of a flavoring agent.

67. The aqueous pharmaceutical suspension according to claim 66 , wherein the flavoring agent is artificial raspberry cream flavor or artificial orange cream flavor.

68. The aqueous pharmaceutical suspension according to claim 67 , wherein the flavoring agent is artificial raspberry cream flavor or artificial orange cream flavor.

69. The aqueous pharmaceutical suspension according to claim 68 , wherein the flavoring agent is artificial raspberry cream flavor or artificial orange cream flavor.

70. The aqueous pharmaceutical suspension according to claim 3 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.15% of edetate disodium, 0.034% of propylparaben, 0.017% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 20% of sucrose, and 10% of xylitol.

71. The aqueous pharmaceutical suspension according to claim 70 , further comprising, by weight/volume (g/100 mL), 0.1% of titanium dioxide.

72. The aqueous pharmaceutical suspension according to claim 71 , further comprising, by weight/volume (g/100 mL), 0.4% of raspberry cream flavor.

73. The aqueous pharmaceutical suspension according to claim 3 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.15% of edetate disodium, 0.034% of propylparaben, 0.017% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 10% of sucrose, and 10% of xylitol.

74. The aqueous pharmaceutical suspension according to claim 73 , further comprising, by weight/volume (g/100 mL), 0.1% of titanium dioxide.

75. The aqueous pharmaceutical suspension according to claim 74 , further comprising, by weight/volume (g/100 mL), 0.4% of raspberry cream flavor.

76. The aqueous pharmaceutical suspension according to claim 3 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.15% of edetate disodium, 0.034% of propylparaben, 0.017% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 20% of sucrose, and 10% of sorbitol solution.

77. The aqueous pharmaceutical suspension according to claim 76 , further comprising, by weight/volume (g/100 mL), 0.1% of titanium dioxide.

78. The aqueous pharmaceutical suspension according to claim 77 , further comprising, by weight/volume (g/100 mL), 0.4% of raspberry cream flavor.

79. The aqueous pharmaceutical suspension according to claim 4 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.15% of edentate disodium, 0.034% of propylparaben 0.017% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 20% of sucrose, and 10% of sorbitol solution.

80. The aqueous pharmaceutical suspension according to claim 79 , further comprising, by weight/volume (g/100 mL), 0.1% of titanium dioxide.

81. The aqueous pharmaceutical suspension according to claim 80 , further comprising, by weight/volume (g/100 mL), 0.4% of raspberry cream flavor.

82. The aqueous pharmaceutical suspension according to claim 1 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.042% of propylparaben 0.021% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 10% of sucrose, and 10% of xylitol.

83. The aqueous pharmaceutical suspension according to claim 1 , comprising, by weight/volume (g/100 mL), 0.60% of fexofenadine zwitterionic dihydrate Form I, 2.5% of propylene glycol, 0.042% of propylparaben 0.021% of butylparaben, 0.35% of xanthan gum, 0.05% of Poloxamer 407, 1.25% of sodium phosphate dibasic heptahydrate, 0.75% of sodium phosphate monobasic monohydrate, 20% of sucrose, and 10% of xylitol.

84. The aqueous pharmaceutical suspension according to claim 1 , wherein the sweetener system comprises, by weight/volume (g/100 mL), 10% to 40% sucrose; and 20% xylitol.

85. The aqueous pharmaceutical suspension according to claim 1 , wherein the sweetener system comprises, by weight/volume (g/100 mL), 10% to 20% sucrose, and 10% to 20% xylitol.

86. An aqueous pharmaceutical suspension, having a pH 5.8 to 7.0 adjusted by a buffer system, wherein the suspension comprises, by weight/volume (g/100 mL),

0.60% of fexofenadine zwitterionic dihydrate Form I of formula (I) having a particle size of less than 40 μm for at least 90% of the fexofenadine zwitterionic dihydrate Form I;

0.01% to 0.20% of a wetting agent;

a suspending agent selected from 0.10% to 0.50% of a hydrocolloid gum, or 0.1% to 1.0% of hydroxyethylcellulose;

a sweetener system comprising

10% to 40% of sucrose or invert sucrose; and

10% to 20% of xylitol, sorbitol or sorbitol solution, or maltitol solution;

provided that the ratio of the amount of (sucrose or invert sucrose):(xylitol, sorbitol or sorbitol solution, or maltitol solution) is 1:1 to 2:1; and

a preservative system comprising

0.010% to 0.058% of propylparaben, sodium propylparaben or potassium propylparaben;

0.0005% to 0.0350% of butylparaben or sodium butylparaben; and

0.06% to 0.26% of edetate disodium, 0.01% to 0.27% of benzoic acid or sodium benzoate, 0.01% to 0.30% of sorbic acid or potassium sorbate or 0.10% to 1.50% of benzyl alcohol.

87. The aqueous pharmaceutical suspension according to claim 86 , comprising, by weight/volume (g/100 mL), 2.5% of propylene glycol; 0.05% of Poloxamer 407; 0.35% of xanthan gum; 10% to 20% of sucrose; 10% of xylitol or sorbitol; 0.034% of propylparaben; 0.017% of butylparaben; 0.15% of edetate disodium; and wherein the buffer system comprises, by weight/volume (g/100 mL), 1.25% of sodium phosphate dibasic heptahydrate and 0.75% of sodium phosphate monobasic monohydrate.

88. The aqueous pharmaceutical suspension according to claim 86 , comprising, by weight/volume (g/100 mL), 20% of sucrose and 10% of xylitol.