Taste masking compositions comprising spray dried microcapsules containing sucralfate and methods for preparing same

• US 5,013,557 A
• Filed: 10/03/1989
• Issued: 05/07/1991
• Est. Priority Date: 10/03/1989
• Status: Expired due to Fees

• Current Assignee: Warner-Lambert Company (Pfizer Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Tai, Anna W.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/416,630
• Time in Patent Office: 581 Days
• Field of Search: 424/501, 424/493, 424/499, 424/498, 424/500, 424/489, 424/78, 424/439, 424/440, 424/442, 427/3
• US Class Current: 424/493
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin

Abstract

The present invention pertains to spray dried spheroidal microcapsules under about 150 microns in diameter which comprise in percentages by weight of the microcapsule composition (a) sucralfate present in an amount from about 1% to about 70%, and (b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%. In another embodiment, the invention is directed at a taste masking composition which comprises a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter and a matrix over the core wherein the taste masking composition comprises (A) a microcapsule core comprising in percentages by weight of the core composition (a) sucralfate present in an amount from about 1% to about 70%, and (b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and (B) a matrix over the core comprising in percentages by weight of the matrix composition (a) a bulking agent present in an amount up to about 99.9%, and (b) a lubricating agent present in an amount from about 0.1% to about 7%.

Claims

1. A spray dried spheroidal microcapsule under about 150 microns in diameter which comprises in percentages by weight of the microcapsule composition:

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%.

2. The microcapsule according to claim 1, wherein sucralfate is present in an amount from about 1% to about 60%, by weight of the microcapsule composition.

3. The microcapsule according to claim 1, wherein the polymer soluble in the gastric fluids is present in an amount from about 40% to about 99%, by weight of the microcapsule composition.

4. The microcapsule according to claim 1, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, acacia, agar, alginic acid, carrageenan, guar, pectin, tragacanth, xanthan, carboxymethyl cellulose, methyl cellulose, microcrystalline cellulose, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrrolidone polymers, and mixtures thereof.

5. The microcapsule according to claim 4, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, alginic acid, and mixtures thereof.

6. The microcapsule according to claim 1, further comprising a plasticizing agent present in an amount from about 5% to about 30%, by weight of the microcapsule composition.

7. The microcapsule according to claim 6, wherein the plasticizing agent is selected from the group consisting of ethylene glycol, propylene glycol, acetyltributylcitrate, and mixtures thereof.

8. The microcapsule according to claim 1, wherein the microcapsule is under about 100 microns in diameter.

9. A taste masking composition which comprises a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter and a matrix over the core wherein the taste masking composition comprises:

(A) a microcapsule core comprising in percentages by weight of the core composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) a matrix over the core comprising in percentages by weight of the matrix composition;

(a) a bulking agent present in an amount up to about 99.9%; and

(b) a lubricating agent present in an amount from about 0.1% to about 7%.

10. The composition according to claim 9, wherein sucralfate is present in an amount from about 1% to about 60%, by weight of the core composition.

11. The composition according to claim 9, wherein the polymer soluble in the gastric fluids is present in an amount from about 40% to about 99%, by weight of the core composition.

12. The composition according to claim 9, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, acacia, agar, alginic acid, carrageenan, guar, pectin, tragacanth, xanthan, carboxymethyl cellulose, methyl cellulose, microcrystalline cellulose, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrrolidone polymers, and mixtures thereof.

13. The composition according to claim 9, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, alginic acid, and mixtures thereof.

14. The composition according to claim 9, wherein the bulking agent is present in an amount up to about 98%, by weight of the matrix composition.

15. The composition according to claim 9, wherein the bulking agent is selected from the group of sugar alcohols consisting of sorbitol, xylitol, mannitol, galactitol, maltitol, and mixtures thereof.

16. The composition according to claim 9, wherein the lubricating agent is present in an amount from about 0.5% to about 6%, by weight of the matrix composition.

17. The composition according to claim 9, wherein the lubricating agent is selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, waxes, and mixtures thereof.

18. The composition according to claim 9, wherein the matrix further comprises a binding agent present in an amount from about 2% to about 15%, by weight of the matrix composition.

19. The composition according to claim 18, wherein the binding agent is selected from the group consisting of pregelatinized starch, sucrose, polyethylene glycol, and mixtures thereof.

20. The composition according to claim 9, wherein the weight ratio of microcapsule core composition to matrix composition is from about 1:

9 to about 9;

1, respectively.

21. A method for preparing spray dried spheroidal microcapsules under about 150 microns in diameter, which comprises the steps of:

(A) providing the following ingredients, in percentages by weight of the microcapsule composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) preparing an aqueous homogeneous mixture of the ingredients in step (A), wherein sucralfate is present in a concentration from about 1% to about 60%, and the polymer soluble in the gastric fluids is present in a concentration from about 5% to about 60%, by weight of the aqueous mixture; and

(C) feeding the mixture of step (B) into a spray dryer and spray drying the mixture under controlled conditions such that spheroidal microcapsules under about 150 microns in diameter are formed.

22. The method according to claim 21, wherein sucralfate is present in an amount from about 1% to about 60%, by weight of the microcapsule composition.

23. The method according to claim 21, wherein the polymer soluble in the gastric fluids is present in an amount from about 40% to about 99%, by weight of the microcapsule composition.

24. The method according to claim 21, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, acacia, agar, alginic acid, carrageenan, guar, pectin, tragacanth, xanthan, carboxymethyl cellulose, methyl cellulose, microcrystalline cellulose, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrrolidone polymers, and mixtures thereof.

25. The microcapsule according to claim 24, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, alginic acid, and mixtures thereof.

26. The method according to claim 21, further comprising a plasticizing agent present in an amount from about 5% to about 30%, by weight of the microcapsule composition.

27. The microcapsule according to claim 26, wherein the plasticizing agent is selected from the group consisting of ethylene glycol, propylene glycol, acetyltributylcitrate, and mixtures thereof.

28. The method according to claim 21, wherein sucralfate in the aqueous mixture of step (B) is prepared in a concentration from about 1% to about 60%, by weight of the aqueous mixture.

29. The method according to claim 21, wherein the polymer soluble in the gastric fluids in the aqueous mixture of step (B) is prepared in a concentration from about 5% to about 60%, by weight of the aqueous mixture.

30. The method according to claim 21, wherein the controlled conditions in the spray drying step of step (C) include an air inlet temperature from about 60°

C. to about 145°

C.

31. The method according to claim 21, wherein the controlled conditions in the spray drying step of step (C) include an air outlet temperature from about 40°

C. to about 90°

C.

32. The method according to claim 21, wherein the spray dried spheroidal microcapsules in step (C) are under about 100 microns in diameter.

33. A method for preparing a taste masking composition which comprises a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter and a matrix over the core which comprises the steps of:

(A) providing the following ingredients of the microcapsule core in percentages by weight of the core composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) preparing an aqueous homogeneous mixture of the ingredients in step (A), wherein sucralfate is present in a concentration from about 1% to about 60%, and the polymer soluble in the gastric fluids is present in a concentration from about 5% to about 60%, by weight of the aqueous mixture; and

(C) feeding the mixture of step (B) into a spray dryer and spray drying the mixture under controlled conditions such that spheroidal microcapsules under about 150 microns in diameter are formed;

(D) providing the following ingredients of the matrix, in percentages by weight of the matrix composition;

(a) a bulking agent present in an amount up to about 99.9%; and

(b) a lubricating agent present in an amount from about 0.1% to about 7%; and

(E) preparing a homogeneous mixture of the ingredients in step (D); and

(F) preparing a homogeneous mixture of the spray dried microcapsules from step (C) and the matrix mixture from step (E) and compressing the homogeneous mixture into tablets.

34. The method according to claim 33, wherein sucralfate in the microcapsule core in step (A) is present in an amount from about 1% to about 60%, by weight of the core composition.

35. The method according to claim 33, wherein the polymer soluble in the gastric fluids in the microcapsule core in step (A) is present in an amount from about 5% to about 60%, by weight of the core composition.

36. The method according to claim 33, wherein the polymer soluble in the gastric fluids is selected from the group consisting of maltodextrins, gelatin, acacia, agar, alginic acid, carrageenan, guar, pectin, tragacanth, xanthan, carboxymethyl cellulose, methyl cellulose, microcrystalline cellulose, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrrolidone polymers, and mixtures thereof.

37. The method according to claim 33, further comprising a plasticizing agent present in an amount from about 5% to about 30%, by weight of the microcapsule composition.

38. The method according to claim 33, wherein the bulking agent in the matrix in step (D) is present in an amount up to about 98%, by weight of the matrix composition.

39. The method according to claim 33, wherein the bulking agent is a sugar alcohol.

40. The method according to claim 33, wherein the lubricating agent is present in an amount from about 0.5% to about 6%, by weight of the matrix composition.

41. The method according to claim 33, wherein the matrix further comprises a binding agent present in an amount from about 2% to about 15%, by weight of the matrix composition.

42. The method according to claim 33, wherein the weight ratio of microcapsule core composition to matrix composition is from about 1:

9 to about 9;

1, respectively.

43. A spray dried spheroidal microcapsule under about 150 microns in diameter prepared by a method which comprises the steps of:

(A) providing the following ingredients, in percentages by weight of the microcapsule composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) preparing an aqueous homogeneous mixture of the ingredients in step (A), wherein sucralfate is present in a concentration from about 1% to about 60%, and the polymer soluble in the gastric fluids is present in a concentration from about 5% to about 60%, by weight of the aqueous mixture; and

(C) feeding the mixture of step (B) into a spray dryer and spray drying the mixture under controlled conditions such that spheroidal microcapsules under about 150 microns in diameter are formed.

44. A taste masking composition which comprises a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter and a matrix over the core prepared by a method which comprises the steps of:

(A) providing the following ingredients of the microcapsule core in percentages by weight of the core composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) preparing an aqueous homogeneous mixture of the ingredients in step (A), wherein sucralfate is present in a concentration from about 1% to about 60%, and the polymer soluble in the gastric fluids is present in a concentration from about 5% to about 60%, by weight of the aqueous mixture; and

(C) feeding the mixture of step (B) into a spray dryer and spray drying the mixture under controlled conditions such that spheroidal microcapsules under about 150 microns in diameter are formed;

(D) providing the following ingredients of the matrix, in percentages by weight of the matrix composition;

(a) a bulking agent present in an amount up to about 99.9%; and

(b) a lubricating agent present in an amount from about 0.1% to about 7%; and

(E) preparing a homogeneous mixture of the ingredients in step (D); and

(F) preparing a homogeneous mixture of the spray dried microcapsules from step (C) and the matrix mixture from step (E) and compressing the homogeneous mixture into tablets.

45. A taste masking composition which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter wherein the microcapsule core composition comprises:

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%.

46. The taste masking composition according to claim 45, wherein the pharmaceutically acceptable carrier is selected from the group consisting of a lozenge, a toffee, a nougat, a suspension, and a chewy candy.

47. A method for preparing a taste masking composition which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a spray dried spheroidal microcapsule core under about 150 microns in diameter which comprises the steps of:

(A) providing the following ingredients, in percentages by weight of the microcapsule composition;

(a) sucralfate present in an amount from about 1% to about 70%; and

(b) a polymer soluble in the gastric fluids present in an amount from about 30% to about 99%; and

(B) preparing an aqueous homogeneous mixture of the ingredients in step (A), wherein sucralfate is present in a concentration from about 1% to about 60%, and the polymer soluble in the gastric fluids is present in a concentration from about 5% to about 60%, by weight of the aqueous mixture; and

(C) feeding the mixture of step (B) into a spray dryer and spray drying the mixture under controlled conditions such that spheroidal microcapsules under about 150 microns in diameter are formed;

(D) heating and mixing the pharmaceutically acceptable carrier in water at an elevated temperature;

(E) cooling the pharmaceutically acceptable carrier to a temperature below about 120°

C.;

(F) preparing a homogeneous mixture of the spray dried microcapsules from step (C) and the pharmaceutically acceptable carrier from step (E); and

(G) forming the resulting mixture into shapes.