Cushioning beads and tablet comprising the same capable of forming a suspension

• US 5,780,055 A
• Filed: 09/06/1996
• Issued: 07/14/1998
• Est. Priority Date: 09/06/1996
• Status: Expired due to Fees

• Current Assignee: University of Maryland
• Original Assignee: University of Maryland Baltimore County (University of Maryland)
• Inventors: Augsburger, Larry L., Shangraw, Ralph, Habib, Yacoub S.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US08/709,415
• Time in Patent Office: 676 Days
• Field of Search: 424/464, 424/489, 424/469, 424/465, 424/494, 424/480
• US Class Current: 424/464
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50

Abstract

Cushioning beads comprising microcrystalline cellulose and a disintegrant (preferably croscarmellose sodium) are disclosed. The cushioning beads are prepared by extrusion-spheronization, followed by freeze-drying. Also disclosed, are water-dispersible tablets having high tensile strength, comprising the cushioning beads and biologically active ingredient-loaded beads, wherein optionally, the tablets can contain a viscosity enhancer in the form of separate beads, or as a component of the biologically active ingredient-loaded beads such that viscosity is rapidly generated when the tablets come in contact with water, and a homogenous suspension is formed, which can be easily swallowed by children and the elderly, with minimal effect of the biologically active ingredient release properties. The tablets are useful for sustained delivery of large doses of biologically active ingredients where swallowing of a large tablet or capsule poses a problem.

Claims

1. A cushioning bead comprising microcrystalline cellulose, wherein said cushioning bead is prepared by extrusion-spheronization, followed by freeze-drying, wherein said cushioning bead has a diameter of about 0.2-2.0 mm.

2. The cushioning bead as claimed in claim 1, wherein said microcrystalline cellulose is present in the cushioning bead in an amount of from about 20-100%.

3. The cushioning bead as claimed in claim 2, wherein said microcrystalline cellulose is present in the cushioning bead in an amount of from about 60-95%.

4. The cushioning bead as claimed in claim 1, wherein said cushioning bead additionally comprises a disintegrant.

5. The cushioning bead as claimed in claim 4, wherein said disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, crospovidone, starch, and pregelatinized starch.

6. The cushioning bead as claimed in claim 5, wherein said disintegrant is croscarmellose sodium.

7. The cushioning bead as claimed in claim 4, wherein said disintegrant is present in the cushioning bead in an amount of from greater than 0-50%.

8. The cushioning bead as claimed in claim 7, wherein said disintegrant is present in the cushioning bead in an amount of from about 5.0-40%.

9. The cushioning bead as claimed in claim 4, wherein the ratio of microcrystalline cellulose to disintegrant is about 1:

0-0.2;

0.8.

10. The cushioning bead as claimed in claim 9, wherein the ratio of microcrystalline cellulose to disintegrant is about 0.95:

0.05-0.6;

0.4.

11. The cushioning bead as claimed in claim 4, wherein said cushioning bead additionally comprises a filler.

12. The cushioning bead as claimed in claim 11, wherein said filler is a water-soluble filler selected from the group consisting of lactose and sorbitol.

13. The cushioning bead as claimed in claim 11, wherein said filler is dibasic calcium phosphate.

14. The cushioning bead as claimed in claim 11, wherein said filler is present in the cushioning bead in an amount of from greater than 0-80%.

15. The cushioning bead as claimed in claim 14, wherein said filler is present in the cushioning bead in an amount of from greater than 0-50%.

16. A tablet comprising:

(i) biologically active ingredient-loaded beads; and

(ii) cushioning beads comprising microcrystalline cellulose, wherein said cushioning beads are prepared by extrusion-spheronization, followed by freeze-drying, wherein said cushioning beads have an average diameter of about 0.2-2.0 mm.

17. The tablet as claimed in claim 16, wherein said microcrystalline cellulose is present in the cushioning beads in an amount of from about 20-100%.

18. The tablet as claimed in claim 17, wherein said microcrystalline cellulose is present in the cushioning beads in an amount of from about 60-95%.

19. The tablet as claimed in claim 16, wherein said cushioning beads additionally comprise a disintegrant.

20. The tablet as claimed in claim 19, wherein said disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, crospovidone, starch, and pregelatinized starch.

21. The tablet as claimed in claim 20, wherein said disintegrant is croscarmellose sodium.

22. The tablet as claimed in claim 19, wherein said disintegrant is present in the cushioning beads in an amount of from greater than 0-50%.

23. The tablet as claimed in claim 22, wherein said disintegrant is present in the cushioning beads in an amount of from about 5.0-40%.

24. The tablet as claimed in claim 19, wherein the ratio of microcrystalline cellulose to disintegrant is about 1:

0-0.2;

0.8.

25. The tablet as claimed in claim 24, wherein the ratio of microcrystalline cellulose to disintegrant is about 0.95:

0.05-0.6;

0.4.

26. The tablet as claimed in claim 19, wherein said cushioning beads additionally comprise a filler.

27. The tablet as claimed in claim 26, wherein said filler is a water-soluble filler selected from the group consisting of lactose and sorbitol.

28. The tablet as claimed in claim 26, wherein said filler is dibasic calcium phosphate.

29. The tablet as claimed in claim 26, wherein said filler is present in the cushioning beads in an amount of from greater than 0-80%.

30. The tablet as claimed in claim 29, wherein said filler is present in the cushioning beads in an amount of from greater than 0-50%.

31. The tablet as claimed in claim 16, wherein said biologically active ingredient is selected from the group consisting of a pharmaceutical, a pesticide and a herbicide.

32. The tablet as claimed in claim 31, wherein said pharmaceutical is selected from the group consisting of potassium chloride, a lithium salt, a nonsteroidal anti-inflammatory drug, a calcium salt, sodium fluoride, pridinol or a salt thereof, dimethindine or a salt thereof, a methyl-xanthine, O-β

-hydroxymethyl-rutoside, butamirate or a salt thereof, codeine or a derivative thereof, noscapine, acetaminophen, a vitamin, a β

-blocker, pyrisuccideanol, ticlopidine, dipyridamole, diazepam, erythromycin or a salt thereof, and doxycycline or a salt thereof.

33. The tablet as claimed in claim 31, wherein said pesticide is selected from the group consisting of clomazone, sulfentrazone and clomazone/trifluralin.

34. The tablet as claimed in claim 31, wherein said herbicide is selected from the group consisting of zeta cypermephrin, cadusafos and bifenthrin.

35. The tablet as claimed in claim 16, said biologically active ingredient-loaded beads are coated with a coating material for controlling or sustaining the release properties of the biologically active ingredient, for taste masking, or for imparting resistance to gastric fluid, or said biologically active ingredient-loaded beads contain said material in the matrix thereof.

36. The tablet as claimed in claim 35, said coating material for controlling or sustaining the release properties of the biologically active ingredient and for taste masking is selected from the group consisting of methylcellulose, hydroxypropyl cellulose, ethylcellulose or a latex derivative thereof, and a methylacrylate ester copolymer.

37. The tablet as claimed in claim 35, said coating material for imparting resistance to gastric fluid is selected from the group consisting of shellac, cellulose acetate phthalate, cellulose acetate trimelliate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, and a methacrylic acid copolymer.

38. The tablet of claim 19, wherein said tablet additionally comprises:

(iii) a viscosity enhancer.

39. The tablet of claim 38, wherein said viscosity enhancer is in the form of individual viscosity enhancer beads.

40. The tablet of claim 38, wherein said viscosity enhancer is present in the biologically active ingredient-loaded beads.

41. The tablet of claim 38, wherein said viscosity enhancer is selected from the group consisting of a carbomer, xanthan gum, guar gum, alginate, dextran, pectin, pregelatinized starch, polysaccharide and a cellulose derivative.

42. The tablet of claim 41, wherein said cellulose derivative is selected from the group consisting of sodium or calcium carboxymethlycellulose, hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

43. The tablet of claim 41, wherein said viscosity enhancer is a carbomer.

44. The tablet of claim 39, wherein said viscosity enhancer beads are produced by extrusion-spheronization using a hydroalcoholic solution.

45. The tablet of claim 16, wherein said cushioning beads and biologically active ingredient-loaded beads each have an average diameter of about 0.2-2.0 mm.

46. The tablet of claim 45, wherein said cushioning beads and biologically active ingredient-loaded beads each have an average diameter of about 0.5-1.5 mm.

47. The tablet of claim 39, wherein said cushioning beads and biologically active ingredient-loaded beads and viscosity enhancer beads each have an average diameter of about 0.2-2.0 mm.

48. The tablet of claim 47, wherein said cushioning beads and biologically active ingredient-loaded beads and viscosity enhancer beads each have an average diameter of about 0.5-1.5 mm.

49. The tablet of claim 16, wherein the weight ratio of cushioning beads to biologically active ingredient-loaded beads is about 20:

80-90;

10.

50. The tablet of claim 49, wherein the weight ratio of cushioning beads to biologically active ingredient-loaded beads is about 50:

50-75;

25.

51. The tablet of claim 38, wherein the viscosity enhancer is present in an amount to achieve an apparent viscosity, at 20°

C., of 30-3000 mPa.s.

52. The tablet of claim 51, wherein the viscosity enhancer is present in an amount to achieve an apparent viscosity, at 20°

C., of 500-1000 mPa.s.

53. An in situ suspension formed by dispersing the tablet of claim 38 in an aqueous solution.