Pharmaceutical excipient having improved compressibility

• US 5,725,883 A
• Filed: 06/07/1995
• Issued: 03/10/1998
• Est. Priority Date: 01/09/1995
• Status: Expired due to Fees

• Current Assignee: J Rettenmaier & Sohne GmbH Company KG
• Original Assignee: Edward Mendell Co., Inc.
• Inventors: Hunter, Edward A., Staniforth, John N., Sherwood, Bob E.
• Primary Examiner(s): Schofer, Joseph L.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US08/486,183
• Time in Patent Office: 1,007 Days
• Field of Search: 424/489, 424/498, 424/490, 514/221
• US Class Current: 424/489
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2036 Silicones; Polysiloxanes
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: Y10S 977/727 formed from biological material
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/775 Nanosized powder or flake, e.g. nanosized catalyst
• CPC Class Codes: Y10S 977/801 Drug
• CPC Class Codes: Y10S 977/89 Deposition of materials, e.g. coating, cvd, or ald
• CPC Class Codes: Y10S 977/896 Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

A microcrystalline cellulose-based excipient having improved compressibility, whether utilized in direct compression, dry granulation or wet granulation formulations, is disclosed. The excipient is an agglomerate of microcrystalline cellulose particles and an effective amount of a surfactant, which, in preferred embodiments is an anionic surfactant present in amounts ranging from about 0.1% to about 0.5%, by weight of the microcrystalline cellulose, wherein the microcrystalline cellulose and surfactant are in intimate association with each other. One preferred anionic surfactant utilized in the novel excipient is sodium lauryl sulfate.

Claims

1. An excipient composition comprising a particulate agglomerate of coprocessed microcrystalline cellulose and a surfactant, said surfactant being present in an amount from about 0.1% to about 0.5% by weight of the microcrystalline cellulose, said microcrystalline cellulose and said surfactant being in intimate association with each other.

2. The composition of claim 1, wherein said surfactant is an ionic surfactant.

3. The composition of claim 1, wherein said ionic surfactant is an anionic surfactant.

4. The composition of claim 3, wherein said anionic surfactant is sodium lauryl sulfate.

5. The composition of claim 3, wherein said anionic surfactant is docusate sodium.

6. The composition of claim 1, wherein said surfactant is included in an amount of from about 0.15% to about 0.4%, based on the weight of said microcrystalline cellulose.

7. The composition of claim 1, wherein said surfactant is included in an amount of from about 0.2% to about 0.3%, based on the weight of said microcrystalline cellulose.

8. The composition of claim 1, wherein said excipient composition comprises particles having an average particle size of from about 10 μ

m to about 1,000 μ

m.

9. The composition of claim 1, wherein said excipient particles have an average particle size of from about 10 μ

m to about 500 μ

m.

10. The composition of claim 1, wherein said excipient particles have an average particle size of from about 30 μ

m to about 250 μ

m.

11. The composition of claim 1, wherein said excipient particles have an average particle size of from about 40 μ

m to about 200 μ

m.

12. The composition of claim 1, wherein said excipient composition has a moisture content from about 0.5% to about 15%.

13. The composition of claim 1, wherein said excipient composition further comprises from about 0.1 to about 20% by weight silicon dioxide, based on the weight of the microcrystalline cellulose.

14. The composition of claim 1, wherein said excipient composition further comprises from about 0.5 to about 10% by weight silicon dioxide, based on the weight of the microcrystalline cellulose.

15. The composition of claim 1, wherein said excipient composition further comprises from about 1.25 to about 5% by weight silicon dioxide, based on the weight of the microcrystalline cellulose.

16. The composition of claim 14, wherein said silicon dioxide is derived from colloidal silicon dioxide.

17. The composition of claim 1, wherein said excipient has a bulk density from about 0.2 g/ml to about 0.5 g/ml.

18. The composition of claim 15, wherein said excipient has a bulk density from about 0.22 g/ml to about 0.35 g/ml.

19. The composition of claim 1, wherein said excipient particles further comprise a member of the group consisting of non-silicon metal oxides, starches, starch derivatives, polyalkylene oxides, celluloses, cellulose ethers, cellulose esters and mixtures thereof.

20. An excipient composition, comprising from about 1% to about 99% of an excipient comprising a particulate agglomerate of coprocessed microcrystalline cellulose and from about 0.1% to about 0.5% of a surfactant by weight of said microcrystalline cellulose, the microcrystalline cellulose and said surfactant being in intimate association with each other, and from about 99% to about 1% of an active ingredient.

21. The composition of claim 20, wherein said surfactant is an ionic surfactant.

22. The composition of claim 21, wherein said ionic surfactant is an anionic surfactant.

23. The composition of claim 21, wherein said anionic surfactant is sodium lauryl sulfate.

24. The composition of claim 21, wherein said anionic surfactant is docusate sodium.

25. The composition of claim 20, wherein said surfactant is included in an amount of from about 0.15% to about 0.4%, based on the weight of said microcrystalline cellulose.

26. The composition of claim 20, wherein said surfactant is included in an amount of from about 0.2% to about 0.3%, based on the weight of said microcrystalline cellulose.

27. The composition of claim 20, further comprising silicon dioxide.

28. The composition of claim 20, which has been wet granulated.

29. The composition of claim 20, which has been incorporated into a solid form.

30. An augmented microcrystalline cellulose excipient suitable for compression into a solid dosage form with a therapeutically active agent via a wet granulation method, comprising particles of microcrystalline cellulose having from about 0.1% to about 0.5% of an anionic surfactant, by weight of said microcrystalline cellulose integrated with said microcrystalline cellulose particles.

31. An excipient composition comprising a particulate agglomerate of coprocessed microcrystalline cellulose, silicon dioxide, and surfactant, said Silicon dioxide and said surfactant being present in an amount by weight of the microcrystalline cellulose which is effective to augment the compressibility of the microcrystalline cellulose, said microcrystalline cellulose, said silicon dioxide, and said surfactant being in intimate association with each other.

32. The composition of claim 31, wherein said surfactant is an ionic surfactant.

33. The composition of claim 31, wherein said ionic surfactant is an anionic surfactant.

34. The composition of claim 33, wherein said anionic surfactant is sodium lauryl sulfate.

35. The composition of claim 33, wherein said anionic surfactant is docusate sodium.

36. The composition of claim 31, wherein said surfactant is included in an amount of from about 0.1% to about 5.0%, based on the weight of said microcrystalline cellulose.

37. The composition of claim 31, wherein said surfactant is included in an amount of from about 0.1% to about 0.5%, based on the weight of said microcrystalline cellulose.

38. The composition of claim 31, wherein said surfactant is included in an amount of from about 0.15% to about 0.4%, based on the weight of said microcrystalline cellulose.

39. The composition of claim 31, wherein said surfactant is included in an amount of from about 0.2% to about 0.3%, based on the weight of said microcrystalline cellulose.

40. The composition of claim 31, wherein said excipient composition comprises particles having an average particle size of from about 10 μ

m to about 1,000 μ

m.

41. The composition of claim 31, wherein said excipient particles have an average particle size of from about 10 μ

m to about 500 μ

m.

42. The composition of claim 31, wherein said excipient particles have an average particle size of from about 30 μ

m to about 250 μ

m.

43. The composition of claim 31, wherein said excipient particles have an average particle size of from about 40 μ

m to about 200 μ

m.

44. The composition of claim 31, wherein said excipient composition has a moisture content from about 0.5% to about 15%.

45. The composition of claim 31, wherein said silicon dioxide is included in an amount of from about 0.1 to about 20%, based on the weight of the microcrystalline cellulose.

46. The composition of claim 31, wherein said silicon dioxide is included in an amount of from about 0.5 to about 10%, based on the weight of the microcrystalline cellulose.

47. The composition of claim 31, wherein said silicon dioxide is included in an amount of from about 1.25 to about 5%, based on the weight of the microcrystalline cellulose.

48. The composition of claim 31, wherein said silicon dioxide is derived from colloidal silicon dioxide.

49. The composition of claim 31, wherein said excipient has a bulk density from about 0.2 g/ml to about 0.5 g/ml.

50. The composition of claim 47, wherein said excipient has a bulk density from about 0.22 g/ml to about 0.35 g/ml.

51. The composition of claim 31, wherein said excipient particles further comprise a member of the group consisting of non-silicon metal oxides, starches, starch derivatives, polyalkylene oxides, celluloses, cellulose ethers, cellulose esters and mixtures thereof.

52. An excipient composition comprising

from about 1% to about 99% of an excipient including a particulate agglomerate of coprocessed microcrystalline cellulose, from about 0.1% to about 5.0% of a surfactant by weight of said microcrystalline cellulose, and silicon dioxide, the microcrystalline cellulose, the silicon dioxide, and said surfactant being in intimate association with each other;

and

from about 99% to about 1% of an active ingredient.

53. The composition of claim 52, wherein said surfactant is an ionic surfactant.

54. The composition of claim 53, wherein said ionic surfactant is an anionic surfactant.

55. The composition of claim 53, wherein said anionic surfactant is sodium lauryl sulfate.

56. The composition of claim 53, wherein said anionic surfactant is docusate sodium.

57. The composition of claim 52, wherein said surfactant is included in an amount of from about 0.15% to about 0.4%, based on the weight of said microcrystalline cellulose.

58. The composition of claim 52, wherein said surfactant is included in an amount of from about 0.2% to about 0.3%, based on the weight of said microcrystalline cellulose.

59. The composition of claim 52, which has been wet granulated.

60. The composition of claim 52, which has been incorporated into a solid form.